Healing of erosions in rheumatoid arthritis remains elusive: results with 24 months of the anabolic agent teriparatide.

Objective: Erosion healing in rheumatoid arthritis (RA) is difficult to demonstrate. This extension study aimed to determine whether 2 years of teriparatide (TPTD) produces erosion healing. Method: Subjects in a previous 12 month randomized controlled trial of TPTD in RA were invited to receive 12 additional months of open-label TPTD. Eleven of the 24 original subjects were enrolled in the extension study, six of whom received TPTD in the final 12 months only. Subjects receiving 24 months of TPTD were assessed for reduction in erosion volume from baseline using computed tomography. We also compared erosion volumes between 12 and 24 months of TPTD. Large erosions in subjects receiving TPTD for 24 months were examined for volume change. Results: In the six patients who received 24 months of TPTD, there was no significant change in erosion volume at the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints compared with baseline. The six subjects who received 24 months of TPTD had similar changes in erosion volume to the five who received 12 months of TPTD, in MCP (p = 0.17) and PIP (p = 0.63) joints. Assessment of large erosions in those receiving TPTD for 24 months showed no evidence of erosion healing. Conclusion: While this extension study was too small to be conclusive, we observed no evidence of reduction in erosion volume with the addition of TPTD for 24 months in subjects with RA in whom disease activity was controlled on a tumour necrosis factor inhibitor. This is consistent with our negative findings at 12 months.

Comparison of the effects of tocilizumab monotherapy and adalimumab in combination with methotrexate on bone erosion repair in rheumatoid arthritis.

OBJECTIVE: To compare the effects of interleukin-6 (IL-6) receptor and tumour necrosis factor inhibition on inducing repair of existing bone erosions in patients with very early rheumatoid arthritis (RA). METHODS: Prospective non-randomised observational study in patients with active erosive RA with inadequate response to methotrexate (MTX) receiving either tocilizumab (TOC) monotherapy or adalimumab (ADA) with MTX for 52 weeks. Erosion volumes were assessed in metacarpal heads (MCH) and the radius by high-resolution peripheral quantitative CT at baseline and after 52 weeks. Clinical response was monitored using Clinical Disease Activity Index, Simple Disease Activity Index and Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) scores every 12 weeks. RESULTS: TOC (N=33) and ADA/MTX (N=33) treatment groups were balanced for age, sex, body mass index, comorbidities, disease and activity, functional state, autoantibody status, baseline bone damage and baseline bone biomarkers. Both TOC (DAS28-ESR: baseline: 6.2±0.5; 52 weeks: 2.3±1.0) and ADA/MTX (6.3±0.6; 2.8±1.2) significantly reduced disease activity. Erosion volumes significantly decreased in the MCH and radius of patients with RA treated with TOC (p<0.001) but not in patients treated with ADA/MTX (p=0.77), where they remained stable in size. Mean decrease in erosion volume in TOC-treated patients was -1.0±1.1 mm3 and -3.3±5.9 mm3 in the MCH and radius of TOC-treated patients, respectively, and -0.05±0.9 mm3 and -0.08±4.1 mm3 in patients treated with ADA/MTX. CONCLUSIONS: The REBONE study shows that TOC monotherapy achieves more pronounced repair of existing bone erosions than ADA/MTX. Hence, IL-6 is a central factor for the disturbed bone homeostasis in the joints of patients with RA.

Examiners' influence on the measured active and passive extension deficit in finger joints affected by Dupuytren disease.

BACKGROUND: The most commonly reported outcome measure in Dupuytren disease is the extension deficit in finger joints. This study aimed to investigate the examiners' influence on the measured difference between active and passive extension deficit. METHODS: A prospective cohort study was conducted on 157 consecutive patients (81% men, mean age 70 years) scheduled for collagenase treatment for Dupuytren disease. Before injection, one of three experienced hand therapists measured active extension deficit (AED) and passive extension deficit (PED) in the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the affected fingers using a hand-held metal goniometer. We included joints with ≥10° AED, and calculated mean AED and PED in MCP and PIP joints measured by each examiner. For adjusted analysis we used a mixed effects model to determine the relationship between the examiner and the AED-PED difference. RESULTS: For all 291 joints measured, mean AED was 46° (SD 21) and mean PED was 37° (SD 23). Mean difference between AED and PED measured by examiner 1 was 6° (SD 6), by examiner 2 was 9° (SD 9), and by examiner 3 was 12° (SD 9). The mixed effects model analysis showed that the identity of the examining therapist was a significant determinant of the AED-PED difference. CONCLUSIONS: In Dupuytren disease measurement of active and passive extension deficit in finger joint contractures may vary significantly between different examiners. This must be taken into consideration when designing clinical studies and comparing outcomes between studies.

The risk of skin tear in Dupuytren's disease when treated with collagenase.

INTRODUCTION: The purpose of this study was to explore if there was a correlation between joint level and degree of contracture on the one hand and the risk of skin tear in Dupuytren's disease (DD) on the other, when treated with collagenase from Clostridium histolyticum. No trial or study has explored the risk of skin tear as primary outcome in a population that has not been treated for DD before. METHODS: A retrospective study of prospectively collected data was performed on patients with DD treated with collagenase from 1 August 2012 to 1 April 2014. Skin tear was classified as "Yes" or "No" and not quantified by tear size for further analysis. RESULTS: A total of 105 contractures in 90 patients with DD were included. In all, 77 contractures at the metacarpophalangeal (MP) joint and 28 at the proximal interphalangeal joint (PIP) joint. A total of 59 contractures experienced skin tear. The relative risk (RR) of skin tear was 1.5 for an MP joint of ≥ 60° contracture compared with an MP joint at 20-59° (p = 0.17). The RR of skin tear was 2.2 for a PIP joint of ≥ 60° contracture compared to a PIP joint of 20-59° (p = 0.04). The RR for skin tear was 1.1 for an MP joint compared with the PIP joint (p = 0.74). The RR for skin tear was 1.7 for contractures of ≥ 60° compared to 20-59° regardless of level (p = 0.01). CONCLUSIONS: There is a significantly higher relative risk of skin tear when the contracture is ≥ 60° and when the contracture is ≥ 60° and located at the PIP joint. The most important factor regarding the risk of skin tear is the degree of the contracture. FUNDING: none. TRIAL REGISTRATION: approved by the Danish Data Protection Agency.

C2K77 ELISA detects cleavage of type II collagen by cathepsin K in equine articular cartilage.

OBJECTIVES: Develop a species-specific ELISA for a neo-epitope generated by cathepsin K cleavage of equine type II collagen to: (1) measure cartilage type II collagen degradation by cathepsin K in vitro, (2) identify cytokines that upregulate cathepsin K expression and (3) compare cathepsin K with matrix metalloproteinase (MMP) collagenase activity in stimulated cartilage explants and freshly isolated normal and osteoarthritic (OA) articular cartilages. DESIGN: A new ELISA (C2K77) was developed and tested by measuring the activity of exogenous cathepsin K on equine articular cartilage explants. The ELISA was then employed to measure endogenous cathepsin K activity in cultured cartilage explants with or without stimulation by interleukin-1 beta (IL-1ß), tumour necrosis-alpha (TNF-α), oncostatin M (OSM) and lipopolysaccharide (LPS). Cathepsin K activity in cartilage explants (control and osteoarthritic-OA) and freshly harvested cartilage (control and OA) was compared to that of MMPs employing C2K77 and C1,2C immunoassays. RESULTS: The addition of Cathepsin K to normal cartilage caused a significant increase (P < 0.01) in the C2K77 epitope release. Whereas the content of C1,2C, that reflects MMP collagenase activity, was increased in media by the addition to cartilage explants of TNF-α and OSM (P < 0.0001) or IL-1ß and OSM (P = 0.002), no change was observed in C2K77 which also unchanged in OA cartilages compared to normal. CONCLUSIONS: The ELISA C2K77 measured the activity of cathepsin K in equine cartilage which was unchanged in OA cartilage. Cytokines that upregulate MMP collagenase activity had no effect on endogenous cathepsin K activity, suggesting a different activation mechanism that requires further study.

Effects of Teriparatide on Joint Erosions in Rheumatoid Arthritis: A Randomized Controlled Trial.

OBJECTIVE: Articular erosions correlate with disability in rheumatoid arthritis (RA). Biologic agents reduce erosion progression in RA, but erosion healing occurs infrequently. This study was undertaken to assess the effects of the anabolic agent teriparatide on joint erosion volume in RA patients treated with a tumor necrosis factor inhibitor (TNFi). METHODS: We conducted a randomized controlled trial in 24 patients with erosive RA, osteopenia, and disease activity controlled by TNFi treatment for at least 3 months. Half were randomized to receive teriparatide for 1 year and the others constituted a wait-list control group. Subjects and primary rheumatologists were not blinded with regard to treatment assignment, but all outcomes were assessed in a blinded manner. The primary outcome measure was change in erosion volume determined by computed tomography at 6 anatomic sites. Significance within each hand and anatomic site was based on a 2-tailed test, with P values less than 0.05 considered significant. RESULTS: Baseline characteristics of the treatment groups were well balanced. After 52 weeks, the median change in erosion volume in the teriparatide group was -0.4 mm3 (interquartile range [IQR] -34.5, 29.6) and did not differ significantly from that in controls (median change +9.1 mm3 [IQR -29.6, 26.4]) (P = 0.28). No significant difference in change in erosion volume was noted at the radius, ulna, or metacarpophalangeal joints. Bone mineral density improved at the femoral neck and lumbar spine in the teriparatide group. CONCLUSION: Our findings indicate that teriparatide treatment for 1 year does not significantly reduce erosion volume in the hands or wrists of patients with established RA with disease activity controlled by TNFi treatment.

Suppression of Cartilage Degradation by Zingerone Involving the p38 and JNK MAPK Signaling Pathway.

Zingerone, an active compound that is present in cooked ginger, has been claimed to be a bioactive ingredient that holds the potential of preventing and/or treating diseases involving inflammation. In this study, zingerone was used to discover its properties against joint inflammation using interleukin-1ß-induced osteoarthritis in cartilage explant and cell culture models. Zingerone was supplemented into the cartilage explant and cell culture media at different concentrations along with the presence of interleukin-1ß, an inducer of osteoarthritis. Markers indicating cartilage degradation, inflammation, and the signaling molecules involved in the inflammatory induction were investigated. Diacerien, an anti-osteoarthritic drug, was used as a positive control. Zingerone at a concentration of 40 µM reduced the level of matrix metalloproteinase-13 to about 31.95 ± 4.33 % compared with the interleukin-1ß-treated group and halted cartilage explant degradation as indicated by reducing the accumulative release of sulfated glycosaminoglycans by falling to the control concomitantly with an elevation of the remaining contents of uronic acid and collagen in the explant tissues when zingerone was added. In the SW1353 cell line model, zingerone efficiently suppressed the expression of TNF-α, interleukin-6, and interleukin-8 mRNA levels and tended to reduce the levels of both p38 and c-Jun N-terminal kinase phosphorylation. From the results of this study, it can be concluded that zingerone potentially reduced cartilage degradation, which is partially involved in p38 and c-Jun N-terminal kinases of the mitogen activator protein kinase signaling pathway leading to the reduction of proinflammatory cytokine amplification effects and cartilage-degrading enzyme syntheses. This finding supports the contention that ginger holds positive pharmaceutical effects against osteoarthritis.

Decrease in articular hypoxia and synovial blood flow at early time points following infliximab and etanercept treatment in rheumatoid arthritis.

OBJECTIVES: An important feature of rheumatoid arthritis (RA) is hypoxia-driven synovial angiogenesis, but the relationship between change in vascularity, as measured by power Doppler ultrasound (PDUS), and oxygen tensions is unaddressed. METHODS: Metacarpophalangeal (MCP) joint PDUS was assessed in 23 patients with RA, alongside arthroscopic synovitis and oxygen tension measurements, at baseline and 4 weeks after anti-tumour necrosis factor (TNF) inhibitors. RESULTS: Anti-TNF reduced PDUS scores, which were negatively correlated with rise in oxygen tensions. The latter was related to good EULAR response at week 52. CONCLUSIONS: Anti-TNF results in rapid reduction in synovial blood flow, with a corresponding rise in oxygen tension most marked in EULAR good responders.

Comparison of Treatment Outcome After Collagenase and Needle Fasciotomy for Dupuytren Contracture: A Randomized, Single-Blinded, Clinical Trial With a 1-Year Follow-Up.

PURPOSE: This study compared the efficacy of collagenase treatment and needle fasciotomy for contracture of the metacarpophalangeal (MCP) joint in Dupuytren disease. METHODS: This is a prospective, single-blinded, randomized study with follow-up 1 week and 1 year after treatment. One hundred and forty patients with an MCP contracture of 20° or more in a single finger were enrolled, of whom 69 patients were randomized to collagenase treatment and 71 patients to needle fasciotomy. The patients were followed at 1 week and were examined by a physiotherapist after 1 year. Measurements of joint movement and grip strength were recorded as well as patient-perceived outcomes measured by the Unité Rhumatologique des Affections de la Main (URAM) questionnaire and a visual analog scale (VAS) for the estimation of procedural pain and subjective treatment efficacy. RESULTS: Eighty-eight percent of the patients in the collagenase group and 90% of the patients in the needle fasciotomy group had a reduction in their MCP contracture to less than 5° 1 week after treatment, and the median gains in passive MCP movement were 48° and 46°, respectively. The median VAS score for procedural pain was 4.9 of 10 in the collagenase group and 2.7 of 10 in the needle fasciotomy group. After 1 year, 90% of the patients in both groups had full extension of the treated MCP joint. One patient in each group had a recurrence of the contracture. The median improvement in URAM score was 8 units in both groups and the VAS estimation of treatment efficacy by the patients was 8.7 of 10 in both groups. CONCLUSIONS: There was no significant difference between the treatment outcomes after collagenase and needle fasciotomy treatment after 1 year. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

Collagenase treatment of Dupuytren's contracture using a modified injection method: a prospective cohort study of skin tears in 164 hands, including short-term outcome.

BACKGROUND AND PURPOSE: Treatment of Dupuytren's contracture (DC) with collagenase Clostridium histolyticum (CCH) consists of injection followed by finger manipulation. We used a modified method, injecting a higher dose than recommended on the label into several parts of the cord, which allows treatment of multiple joint contractures in 1 session and may increase efficacy. We studied the occurrence of skin tears and short-term outcome with this procedure. PATIENTS AND METHODS: We studied 164 consecutive hands with DC, palpable cord, and extension deficit of ≥ 20º in the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joint (mean patient age 70 years, 82% men). A hand surgeon injected all the content of 1 CCH vial (approximately 0.80 mg) into multiple spots in the cord and performed finger extension under local anesthesia after 1 or 2 days. A nurse recorded skin tears on a diagram and conducted a standard telephone follow-up within 4 weeks. A hand therapist measured joint contracture before injection and at a median of 23 (IQR: 7-34) days after finger extension. RESULTS: A skin tear occurred in 66 hands (40%). The largest diameter of the tear was ≤ 5 mm in 30 hands and > 10 mm in 14 hands. Hands with skin tear had greater mean pretreatment MCP extension deficit than those without tear: 59º (SD 26) as opposed to 32º (SD 23). Skin tear occurred in 21 of 24 hands with MCP contracture of ≥ 75º. All tears healed with open-wound treatment. No infections occurred. Mean improvement in total (MCP + PIP) extension deficit was 55º (SD 28). INTERPRETATION: Skin tears occurred in 40% of hands treated with collagenase injections, but only a fifth of them were larger than 1 cm. Tears were more likely in hands with severe MCP joint contracture. All tears healed without complications. Short-term contracture reduction was good.

Inflammation and vascularisation markers of arthroscopically-guided finger joint synovial biospies reflect global disease activity in rheumatoid arthritis.

OBJECTIVES: To analyse whether synovial markers of the clinically dominant metacarpophalangeal (MCP) joint reflect global disease activity measures in rheumatoid arthritis (RA). METHODS: Arthroscopically-guided synovial biopsies from the dominant metacarpophalangeal (MCP) joint of 10 patients with RA (DAS28 >3.2) were stained for determination of the synovitis score, CD68, vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α). MRI and ultrasound were used to calculate the RAMRIS and US7 score respectively. Arthroscopy of the same joint was repeated in 6 patients after 6 months. RESULTS: The synovitis score significantly correlated to DAS28 (Spearman r=0.74), CRP (r=0.69), and US7 (r=0.66); sublining CD68 macrophages to CRP (r=0.6); HIF-1α to DAS28 (r=0.77), CRP (r=0.73); and VEGF to DAS28 (r=0.753) and RAMRIS (r=0.663). All patients showed a reduction of the DAS28 after 6 months (mean±SD: 5.2±1.5 vs. 2.75±1.1; p<0.05). There were three patients with a good EULAR response, and only these showed declining sublining CD68 macrophages in the control biopsy (χ2 test: LR 8.3, p=0.05). Two of the remaining patients with increasing CD68 sublining macrophages showed a deterioration of the RAMRIS. CONCLUSIONS: Some histological findings in arthroscopically-guided biopsies of the dominantly affected MCP joint reflect global disease activity measures and their changes in RA patients. Moreover, repeated MCP synovial biopsy may distinguish true responders from individuals with residual disease activity, who are not readily recognized by clinical means.

Efficacy and safety of concurrent collagenase clostridium histolyticum injections for multiple Dupuytren contractures.

PURPOSE: To assess the safety and efficacy of 2 concurrent injections of collagenase clostridium histolyticum (CCH) in the same hand to treat multiple Dupuytren flexion contractures. METHODS: In a multicenter, open-label phase IIIb study, 60 patients received two 0.58-mg CCH doses injected into cords affecting 2 joints in the same hand during 1 visit, followed by finger extension approximately 24 hours later. Efficacy at postinjection day 30 (change in flexion contracture and active range of motion, patient satisfaction, physician-rated improvement, and rates of clinical success [flexion contracture 5° or less]) and adverse events were summarized. RESULTS: The concurrent injections were most commonly administered in cords affecting metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints on the same finger (47%) or 2 MCP joints on different fingers of the same hand (37%). Mean total (sum of the 2 treated joints) flexion contracture decreased 76%, from 87° to 24° (MCP joints: 86%; PIP joints: 66%). Mean total range of motion increased from 100° to 161°. Clinical success was 76% for MCP joints and 33% for PIP joints. Most patients were very satisfied (60%) or quite satisfied (28%) with treatment. Most investigators rated treated joints as very much improved (55%) or much improved (37%). The most common treatment-related adverse events (> 75% of patients) were contusion, pain in extremity, and edema peripheral (local edema). Most adverse events were mild to moderate in severity. Serious complications included 1 pulley rupture related to study medication and 1 flexor tendon rupture (following conclusion of the study). There were no systemic complications. CONCLUSIONS: Results suggest that 2 affected joints can be effectively and safely treated with concurrent CCH injections. There was an increased incidence of some adverse events with concurrent treatment (pruritus, lymphadenopathy, blood blister, and skin laceration) compared with treatment of a single joint. High degrees of patient satisfaction and physician-rated improvement were reported. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

[Treatment of Dupuytren's disease with collagenase - a 1-year follow-up of 37 patients]. / Behandlung der Dupuytren'schen Kontraktur mit Kollagenase - Ein-Jahres-Follow-up-Analyse anhand von 37 Patienten.

INTRODUCTION: The efficiency of collagenase of Clostridium histolyticum (CCH; Xiapex) in the treatment of Dupuytren's contracture has been proved in phase III studies. This retrospective study aims to evaluate our clinical results after the use of CCH. PATIENTS AND METHODS: The study included 40 Dupuytren's contractures in 37 patients. There were 32 male and 5 female patients; their average age was 66 years. The most affected finger was the ring finger (55%; 22/40), followed by the little finger (30%; 12/40) and the middle finger (15; 6/40). 14 fingers (35%) presented isolated contractures of the metacarpophalangeal joint whereas an isolated contracture of the proximal interphalangeal joint was evident in 8 (20%) fingers. 18 (45%) fingers presented combined MCP and PIP flexion contractures. None of the patients underwent any treatment prior to this study. A retrospective chart review was performed of all patients. Follow-up examinations were performed seven days, fourteen days, three months, six months and one year after the intervention. The follow-up examination included goniometry of each affected finger to assess the range of motion (ROM) before and after cord breaking. Further patient-reported outcome was accessed concerning postinterventional complaints, impairment of sensibility and satisfaction with the treatment. RESULTS: The range of motion improved in all fingers. Full extension of the affected finger without any contracture could be observed in 93% of the MCP contractures, 38% of the PIP contractures and in 28% of the combined MCP and PIP contractures. Incomplete cord breaking could be observed in 9 (22.5%) fingers. In 8 fingers (20%) skin tears occurred after joint manipulation but healed up without any further surgical intervention. The recurrence rate at the latest follow-up was 2.5% (1/40). Patient satisfaction was high and none of the patients reported any complaints at the latest follow-up. CONCLUSION: The best results could be achieved in patients with isolated contractures of the MCP joint. Regarding the good functional results, the low complication rates and the high patient satisfaction, CCH represents a simple and effective treatment for Dupuytren's contracture in selected cases.

Pattern of bone erosion and bone proliferation in psoriatic arthritis hands: a high-resolution computed tomography and radiography follow-up study during adalimumab therapy.

OBJECTIVES: To investigate the pattern and development of bone erosion and proliferation in patients with psoriatic arthritis (PsA) during treatment with adalimumab, using high-resolution computed tomography (CT) and conventional radiography. METHOD: Forty-one biologic-naïve PsA patients were initiated with adalimumab 40 mg subcutaneously every other week. CT and radiography of the 2nd-5th metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints were conducted at baseline (n = 41) and after 24 weeks (n = 32). Changes in bone erosion and proliferation are described and the imaging modalities compared. RESULTS: Ninety percent of bone erosions detected by CT were located in the metacarpal heads, and most frequently in the 2nd-3rd MCP joints. Radial (37%) and ulnar (31%) surfaces were more frequently eroded than dorsal (10%) and palmar (22%) sites. Using CT, bone proliferations were located primarily on the sides of the distal part of the DIP joints (43% of all proliferations), but also proximally in DIP (17%) and MCP joints (27%). For bone erosions and proliferations, respectively, radiography showed a low sensitivity (17% and 26%), but a high specificity (98% and 95%) and accuracy (93% and 87%), with CT as the gold standard reference. Neither CT nor radiography revealed statistically significant changes in bone erosion or proliferation scores between baseline and follow-up. CONCLUSIONS: Patterns of bone erosion and proliferation in PsA hands were revealed in more detail by CT than by radiography. No overall progression or repair could be detected during adalimumab treatment with either of the methods.

Advances in the management of Dupuytren disease: collagenase.

Dupuytren disease (DD) is a benign, generally painless connective tissue disorder affecting the palmar fascia that leads to progressive hand contractures. Mediated by myofibroblasts, the disease most commonly begins as a nodule in the palm or finger, and can progress where pathologic cords form leading to progressive flexion deformity of the involved fingers. The palmar skin overlying the cords may become excessively calloused and contracted and involved joints may develop periarticular fibrosis. Although there is no cure, the sequellae of this affliction can be corrected. This article focuses on the role of collagen in DD and the development of a collagen-specific enzymatic treatment for DD contractures.

Comparison of the response to experimentally induced short-term inflammation in the temporomandibular and metacarpophalangeal joints of horses.

OBJECTIVE: To investigate the relationship between inflammatory responses of the temporomandibular joint (TMJ) and the metacarpophalangeal (MCP) joint in clinically normal horses. ANIMALS: 7 mature horses. PROCEDURES: In each horse, 1 TMJ and 1 MCP joint were injected with lipopolysaccharide (LPS; 0.0025 µg). The contralateral TMJ and MCP joint were injected with saline (0.9% NaCl) solution. Synovial fluid samples were collected from all 4 joints over 24 hours after injection. Concentrations of interleukin-6, tumor necrosis factor-α, transforming growth factor-ß, and total protein were measured via immunoassay. Horses were assessed for clinical signs of joint inflammation at each time point. RESULTS: Concentrations of interleukin-6 were not significantly different between LPS-injected MCP joints and TMJs at any time point. Transforming growth factor-ß concentrations were significantly increased in MCP joints, compared with concentrations in TMJs, at 12 and 24 hours after injection. Tumor necrosis factor-α concentrations were significantly higher in LPS-injected TMJs than in LPS-injected MCP joints at 1 and 6 hours after injection. Total protein concentration did not differ significantly between LPS-injected MCP joints and TMJs. Injection of LPS induced clinical inflammation at all time points; additionally, 2 MCP joints (but no TMJs) had an inflammatory response to injection of saline solution. CONCLUSIONS AND CLINICAL RELEVANCE: The inflammatory response to LPS appeared to be attenuated more quickly in TMJs than in MCP joints of horses. The difference in response suggested that a lack of clinical osteoarthritis in the TMJ of horses could be attributable to a difference in cytokine response.

[Treatment of Dupuytren's contracture by means of injectable collagenase: first clinical experiences]. / Die Behandlung der Dupuytrenschen Kontraktur mittels Kollagenase- Erste klinische Erfahrungen.

Recently a minimal invasive therapeutic option by means of enzymatic lysis of Dupuytren's cord was introduced in Europe under the name Xiapex® (Pfizer, Germany).Here we present our first experiences in clinical application with special remarks on complications.In this study 16 injections on 12 Dupuytren's cords in 8 patients were conducted. The average age of the patients was 62.5 (48-74) years. Constitution and application were carried out according to the manufacturer's guidelines. If both the metacarpophalangeal (MP)- and the proximal interphalangeal (PIP) joint were affected, injections were carried out on different points in time. 5 injections were done for contracture of the MPjoint, 4 injections for the PIPjoint, and 3 injections of both, the MP- and PIPjoint. Before the treatment and after 2 weeks the contracture of the treated joint was measured with use of a goniometer for small joints. Side effects and complications were documented as well as whether patients needed - and if yes, for how many days - a pain medication.Total flexion contracture of treated joints could be significantly reduced from 103°±12° to 37°±9°. In MPjoints the flexion contracture was reduced from 47°±8° to 14°±5° and in PIPjoints from 69°±10° to 37°±11° (p<0.05). 5 treated cords showed no signs of complication, recorded local adverse effects were edema (n=5), erythema (n=4) and tearing of skin (n=2). 6 patients needed pain medication for a maximum of 4 days.Treatment with collagenase appears to be an effective and safe therapeutic option for selective cases. Though the procedure ostensibly seems easy, one must emphasize the need for the appropriate application performed only by professionals with a high level of experience both in anatomical knowledge as well as hand surgical know-how to cope potential complications. The value of the new method in relation to the standard partial aponeurectomy and percutaneous needle fasciotomy needs to be ascertained by further research in order to establish a clear indication for each method of treatment.

Interleukin-1beta-induced extracellular matrix degradation and glycosaminoglycan release is inhibited by curcumin in an explant model of cartilage inflammation.

Osteoarthritis (OA) is a degenerative and inflammatory disease of synovial joints that is characterized by the loss of articular cartilage, for which there is increasing interest in natural remedies. Curcumin (diferuloylmethane) is the main polyphenol in the spice turmeric, derived from rhizomes of the plant Curcuma longa. Curcumin has potent chemopreventive properties and has been shown to inhibit nuclear factor kappaB-mediated inflammatory signaling in many cell types, including chondrocytes. In this study, normal articular cartilage was harvested from metacarpophalangeal and metatarsophalangeal joints of eight horses, euthanized for reasons other than research purposes, to establish an explant model mimicking the inflammatory events that occur in OA. Initially, cartilage explants (N= 8) were stimulated with increasing concentrations of the proinflammatory cytokine IL-1beta to select effective doses for inducing cartilage degeneration in the explant model. Separate cartilage explants were then cotreated with IL-1beta at either 10 ng/mL (n= 3) or 25 ng/mL (n= 3) and curcumin (0.1 micromol/L, 0.5 micromol/L, 1 micromol/L, 10 micromol/L, and 100 micromol/L). After 5 days, the percentage of glycosaminoglycan (GAG) release from the explants was assessed using a dimethylmethylene blue colorimetric assay. Curcumin (100 micromol/L) significantly reduced IL-1beta-stimulated GAG release in the explants by an average of 20% at 10 ng/mL and 27% at 25 ng/mL back to unstimulated control levels (P < 0.001). Our results suggest that this explant model effectively simulates the proinflammatory cytokine-mediated release of articular cartilage components seen in OA. Furthermore, the evidence suggests that the inflammatory cartilage explant model is useful for studying the effects of curcumin on inflammatory pathways and gene expression in IL-1beta-stimulated chondrocytes.

Pharmacokinetic modeling of dynamic contrast-enhanced MRI of the hand and wrist in rheumatoid arthritis and the response to anti-tumor necrosis factor-alpha therapy.

Dynamic contrast-enhanced MRI (DCE-MRI) of the hand and wrist was performed in 11 patients with rheumatoid arthritis twice before and once 2 weeks after treatment with anti-tumor necrosis factor (TNF)-alpha therapy. A rapid, T1-weighted 3D spoiled gradient echo (SPGR) sequence was used for the dynamic imaging. T1 estimation was performed using similar images obtained at different flip angles. The relative radiofrequency field was estimated from the known T1 of the periarticular fatty marrow. The arterial input function (AIF) was measured at each examination, and normalized to the expected plasma concentration to reduce partial volume effects. Synovial enhancement was modeled to yield values for Ktrans, ve, and vp. Ktrans and ve showed good reproducibility. There was a significant decrease of about 20% in Ktrans after 2 weeks of treatment. This study demonstrates the potential of DCE-MRI and pharmacokinetic modeling to study early changes in inflammatory activity in rheumatoid arthritis following treatment.