MRI-demonstrated outcome of subchondral stress fractures of the knee after treatment with iloprost or tramadol: observations in 14 patients.

OBJECTIVE: To investigate the outcome of subchondral stress fractures (SSF) of the knee after treatment with the prostacyclin analogue Iloprost or the opioid analgesic Tramadol. DESIGN: Case series/retrospective review. SETTING: Tertiary care center. PATIENTS: Fourteen patients with at least a single subchondral stress fracture of the knee, surrounded by bone marrow edema, visible on T1-weighted and short tau inversion recovery magnetic resonance images. INTERVENTIONS: Nine patients had been treated with oral Iloprost (group 1; 11 SSF) and 5 patients with Tramadol (group 2; 5 SSF) for 4 weeks in the course of a double-blind, randomized clinical trial. MR images were obtained at baseline (1 day before the start of treatment), after 3 months, and after 1 year. MAIN OUTCOME VARIABLES: SSF volumes and their rates of change between baseline and follow-up examinations, as determined on T1-weighted images by computer-assisted quantification. RESULTS: After three months, the SSF volumes had decreased by a median of 42.2% in group 1 and increased by a median of 2.2% in group 2 (P = 0.008). After 1 year, the median decrease in SSF volumes was 100.0% in group 1 and 65.7% in group 2 (P = 0.017). CONCLUSION: This small case series suggests that healing of SSF is more pronounced after Iloprost treatment.

Decrease in circulating endothelial cell adhesion molecule and thrombomodulin levels during oral iloprost treatment in rheumatoid arthritis patients: preliminary results.

OBJECTIVE: Rheumatoid arthritis is a chronic inflammatory autoimmune disease with proinflammatory cytokines involved in its pathogenesis. Recently in vitro as well as in vivo studies have shown that iloprost, a stable prostacyclin analogue, can reduce the release of these cytokines. This study was performed to further investigate the anti-inflammatory effects of iloprost by determining plasma adhesion molecules as markers of endothelial cell activation, and plasma thrombomodulin as a parameter of endothelial cell injury in patients with rheumatoid arthritis receiving oral iloprost therapy. METHODS: Plasma thrombomodulin levels and the values of the plasma adhesion molecules VCAM-1 (vascular cell adhesion molecule 1), E-selectin (CD62E), and ICAM-1 (intercellular adhesion molecule 1, CD 54) were measured by ELISA during a 7-day period of treatment with orally-administered iloprost in 14 patients with active rheumatoid arthritis. Finally, the same parameters were determined at the end of the observation period (1 week after the end of therapy). In addition, the disease activity was measured using the DAS (disease activity score) as well as the patients' self-assessed pain severity, and correlated with the changes of plasma adhesion molecule and thrombomodulin levels. RESULTS: The plasma levels of all three adhesion molecules as well as of thrombomodulin significantly decreased under therapy with oral iloprost. After 1 week (day 7 of therapy), the mean percent changes from day 0 were -20.1% for VCAM-1 (p = 0.008), -21.2 for ICAM-1 (p = 0.003), -24.6% for E-selectin (p = 0.001), and -21.7% for thrombomodulin (p = 0.003). This decrease lasted up to 1 week after the end of therapy in the case of VCAM-1 (p = 0.023) and ICAM-1 (p = 0.001). Further analysis of the results revealed additional significant correlations between different parameters of clinical disease activity, thrombomodulin and adhesion molecules. CONCLUSION: This study showed hints towards clinical effects in patients with rheumatoid arthritis receiving oral iloprost therapy. Pathophysiologically, the decrease of adhesion molecules points at an immunomodulating effect of iloprost. The observed thrombomodulin-lowering effect of iloprost may indicate stabilisation of endothelial cell function by diminishing endothelial cell injury.

STIR vs. T1-weighted fat-suppressed gadolinium-enhanced MRI of bone marrow edema of the knee: computer-assisted quantitative comparison and influence of injected contrast media volume and acquisition parameters.

PURPOSE: To compare short tau inversion recovery (STIR) and T1-weighted (T1w) gadolinium (Gd)-enhanced fat-suppressed MRI of bone marrow edema (BME) of the knee, and investigate the influence of injected contrast media volume and variation of major acquisition parameters on apparent BME volume and signal contrast. MATERIALS AND METHODS: STIR and T1w Gd-enhanced fat-suppressed images were obtained from 30 patients with BME of the knee. Two groups of patients were examined with different MR scanners, acquisition parameters, and contrast media volumes. For both sequences, BME volume and signal contrast were assessed by computer-assisted quantification, and were compared through their arithmetic means and correlation coefficients (r(2)). The injected contrast media volume was also correlated with BME volume and signal contrast differences between sequences. RESULTS: A strong correlation between the STIR and Gd-enhanced T1w images was found for BME volume (r(2) = 0.96-0.99) and BME signal contrast (r(2) = 0.86-0.94). Despite the differences in MR acquisition parameters and injected contrast media volume, both sequences depicted an almost identical BME volume in both groups. Contrast media volume showed a moderate correlation (r(2) = 0.40) with BME volume differences. CONCLUSION: STIR is the optimum method for determining the size and signal contrast of BME. The injected contrast media volume appears to have only a limited influence on apparent BME volume.

A 7-day oral treatment of patients with active rheumatoid arthritis using the prostacyclin analog iloprost: cytokine modulation, safety, and clinical effects.

OBJECTIVE: The purpose of this study was to investigate the plasma levels of tumor necrosis factor (TNF)-alpha, its soluble p55 and p75 receptors, ex vivo lipopolysaccharide (LPS)-stimulated TNF-alpha production, and plasma levels of interleukin 6, interleukin 1, and interleukin 10 during a 7-day oral administration of iloprost in patients with active rheumatoid arthritis. METHODS: During oral 7-day administration of the prostacyclin analog iloprost, the plasma levels of TNF-alpha, soluble p55, and p75 TNF-alpha receptors, IL-1, IL-6, and IL-10 and C-reactive protein (CRP) in serum were determined on days -1, 1, 3, 4, 6, and 8 and after a treatment-free follow-up on day 15. In addition, the ex vivo TNF-alpha production in whole blood under LPS-stimulated and -unstimulated conditions were measured. Fifteen patients with active rheumatoid arthritis and baseline TNF-alpha plasma levels of > or =2 pg/ml were included in independent groups receiving 50 microg, 100 microg, or 150 microg iloprost per day in addition to their conventional antirheumatic therapy. The respective dose was given once daily from days 1 to 3 and doubled from days 4 to 7. The tender and swollen joint count (28 joints) and the patients' assessments of pain severity and general feeling (10-cm visual analog scale) were performed on days -1, 4, and 8 (end of treatment) and after a 7-day follow-up. RESULTS: The patients showed decreased TNF-alpha levels during iloprost administration. The decrease in the ex vivo LPS-stimulated TNF-alpha production and plasma levels of the p75 TNF receptor were found to be associated with a decrease in the number of tender joints. Additionally, IL-6 was downregulated. CONCLUSION: A 7-day oral administration of iloprost resulted in a change of in vivo and ex vivo cellular cytokine production, with reductions in TNF-alpha and p75 TNF receptor plasma levels. These changes were associated with clinical improvements in active rheumatoid arthritis.