Selective activation of mast cells in rheumatoid synovial tissue results in production of TNF-alpha, IL-1beta and IL-1Ra.

OBJECTIVES AND DESIGN: To study the consequences of mast cell activation in human synovial tissue. METHODS: Synovial tissue was obtained from 18 RA patients and mast cells was selectively activated in synovial tissue explant cultures. Expression of TNF-alpha, IL-1beta and IL-1Ra were determined and tissue distribution of IL-1beta was studied. RESULTS: Compared to untreated synovia, selective activation of synovial mast cells increased significantly the production of TNF-alpha (0.49 +/- 0.88 vs. 4.56 +/- 3.18 pg/mg wet tissue, p < 0.001) and IL-1beta (0.058 +/- 0.032 vs. 2.55 +/- 1.98 pg/mg wet tissue, p = 0.013). The expression of TNF-alpha and IL-1beta mRNA increased significantly (19-fold (p = 0.009) and 13-fold (p = 0.031), respectively). Mast cell activation induced IL-1beta expression in particular in nearby CD68 positive synovial macrophages. Secretion of IL-1Ra was also increased but to a lesser degree than that of IL-1beta. CONCLUSIONS: Synovial mast cells produce proinflammmatory cytokines and may thus contribute to the inflammation in RA.

Inhibition of c-kit tyrosine kinase by imatinib mesylate induces apoptosis in mast cells in rheumatoid synovia: a potential approach to the treatment of arthritis.

BACKGROUND: Mast cells have been implicated in the pathogenesis of arthritis, but elucidation of their precise role has been hampered by a lack of efficient and selective inhibitors of their function. OBJECTIVE: To elucidate the role of mast cells in the pathogenesis of rheumatoid arthritis (RA) and to assess whether apoptosis of cultured and synovial tissue mast cells can be induced by inhibiting mast cell growth factor receptor, c-kit tyrosine kinase. METHODS AND RESULTS: Double staining with tumour necrosis factor (TNF) alpha and tryptase antibodies showed the presence of TNFalpha positive mast cells in human rheumatoid synovial tissue. Selective activation of mast cells by anti-IgE resulted in production of TNFalpha in synovial tissue cultures. Inhibition of the c-kit tyrosine kinase with imatinib mesylate (1.0-10 micromol/l) induced profound apoptosis in cultured mast cells as judged by typical apoptotic morphology, increased number of apoptotic nucleosomes, and activation of caspases 8 and 9. Importantly, imatinib also induced apoptosis of mast cells in explant cultures of synovial tissue obtained from patients with RA as judged by a TUNEL assay. Inhibition of c-kit tyrosine kinase was accompanied by significant reduction of TNFalpha production in synovial tissue cultures. CONCLUSION: Mast cells may have a role in the pathogenesis of RA, and inhibition of c-kit may be a new means of inhibiting mast cell activity and of abrogating the contribution of mast cells to synovial inflammation in RA.

Arthrodesis of the wrist with bioabsorbable fixation in patients with rheumatoid arthritis.

Twenty-four wrist arthrodeses were performed on 18 patients with rheumatoid arthritis using a bioabsorbable self-reinforced poly-L-lactide rod as the fixation device. There was one nonunion which required a re-operation and two nonunions which did not need further treatment. The position of the arthrodesis was ulnar deviation and extension in most patients, and there was high patient satisfaction with 21 of the 24 wrists and satisfactory pain relief in 22 of the 24 wrists. This method for fusing the wrist in patients with rheumatoid arthritis appears reliable and simple to perform.

Complications in the first 1,043 operations where self-reinforced poly-L-lactide implants were used solely for tissue fixation in orthopaedics and traumatology.

This is an analysis from one hospital of the first 1043 operations where pure self-reinforced poly-L-lactide (SR-PLLA) implants have been used alone. The operations were performed between 1988 and 1999 and included 407 orthopaedic patients and 636 trauma patients. There was a total of 107 complications. There were 21 infections but no sinus formation. Failure of fixation was seen in 46 patients. In 936 operations the healing was uneventful.

Long-term results of ankle and triple arthrodeses fixed with self-reinforced polylevolactic acid implants in patients with rheumatoid arthritis.

Self-reinforcing polylevolactic acid (SR-PLLA) implants have been used in arthrodeses of patients with rheumatoid arthritis. No long-term evaluation has been published so far. Two patients (three ankles) with destruction of the ankle joint and seven with destruction of the subtalar joint received ten arthrodeses. One out of three ankle arthrodeses healed and nonunion developed in two. Five out of seven triple arthrodeses attained bony union. Two patients with malunion of the subtalar and talonavicular joints are free of symptoms and need no reoperation. One superficial wound infection healed by oral antibiotics. In one patient, an ankle arthrodesis was performed 6 years after the triple arthrodesis of the left foot. SR-PLLA implants can be used in triple arthrodesis in rheumatoid arthritic patients with good results comparable to those of other studies. The problems with nonunion of ankle arthrodeses noticed in former studies are also attributable to this fixation method.

Long-term results of wrist arthrodeses fixed with self-reinforced polylevolactic acid implants in patients with rheumatoid arthritis.

OBJECTIVE: Implants made of self-reinforcing polylevolactic acid (SR-PLLA) have been successfully used in arthrodeses of patients with rheumatoid arthritis. No lone-term evaluation on bioabsorbable fixation in patients with rheumatoid arthritis has been published so far. METHODS: In this study 21 wrist fusions were performed on 18 patients with rheumatoid arthritis by using SR-PLLA rods as fixation devices. The follow-up time was 3-8 years (mean 5.4 years). RESULTS: The results showed one non-union but no infections or problems associated with the bioabsorbable implants used. CONCLUSION: According to this study, fixation of wrist arthrodesis in patients with rheumatoid arthritis can be performed by using SR-PLLA implants with favourable results. The benefit of this method is the avoidance of the removal operation of fixation devices.

A safe surgical technique for the partial resection of the ruptured spleen. A clinical report.

A consecutive series of 11 patients with an acute blunt splenic injury were treated with a 'safe resection' technique. 57% of the injured spleens (range 35-100%) were saved. None of the patients had any signs of secondary bleeding in control CT scan and the mortality was zero. No second-look laparotomies were performed. Follow-up time was at least two months (range 2 month-6 yr). Operation time was in average 120 min. Total mean peroperative bleeding was 1400 ml. Partial resection may offer patient a change for normal function of the injured spleen. However, it is not yet known what is the critical mass of spleen tissue needed for humans. The follow-up time of the present study is still too short to estimate this fact, but further studies may show the benefit of the present method in avoiding serious long term immunological complications of splenectomy. This present study introduces a novel technique for partial resection of injured spleen. Operation can be performed safely and quickly with a complication risk comparable to splenectomy. Resection is applicable even for multi-trauma patients.

Bone mineral density in fractures treated with absorbable or metallic implants.

Absorbable fixation devices have been clinically used in the fracture treatment for over ten years. No studies have been published where bone mineral density has been measured after bone consolidation comparing absorbable and metallic fixation. In this study the bone mineral density was measured after operative ankle fracture treatment with absorbable self-reinforced polyglycolic acid (SR-PGA) screws (14 patients) or with absorbable self-reinforced polylactic acid (SR-PLLA) screws (eight patients) compared with metallic fixation (17 patients). The overall results were radiologically good in every group. A statistically significant difference in the bone mineral density (BMD) was found only in the distal tibial metaphysis between SR-PGA screw and metallic fixation. The BMD increased in the distal tibia after SR-PGA screw fixation by an average 18.3%. The average change of BMD in the distal tibia after SR-PLLA screw fixation decreased by 6.4% while after metallic fixation the average change of MBD decreased by 18.6%. Bone mineral density measurements in the present study may indicate osteogenetic capacity of polyglycolide implants in the bone after fracture or osteotomy fixation. On the other hand, metallic implants showed negative effects to the bone.

Comparison of costs in ankle fractures treated with absorbable or metallic fixation devices.

The economic costs of ankle fractures treated operatively with self-reinforced polyglycolide acid (SR-PGA) screws, with self-reinforced poly-L-lactide acid (SR-PLLA) screws or with metallic implants was determined. All patients were divided into three groups according to the fixation material used. Open and otherwise complicated fractures were excluded. The total expense of operations in each group was taken into account. The average total cost of an ankle fracture fixed with SR-PGA screws was Pounds 3503. In the SR-PLLA group it was Pounds 3906, and in the metallic group it was Pounds 4514. Total expenses were Pounds 1011 higher in the metallic group than in the SR-PGA group, and consequently, expenses in the metallic group were Pounds 608 higher than in the SR-PLLA group. According to this study, it seems that absorbable fixation devices are more economical than metallic implants in operative treatment of ankle fractures though as part of the differences in total expense in this series is due to the age of the patients and other dissimilarities between these groups, the results have to be interpreted carefully.

Reinsertion of the ruptured ulnar collateral ligament of the metacarpophalangeal joint of the thumb with an absorbable self-reinforced polylactide mini tack.

Total rupture of the ulnar collateral ligament of the first metacarpophalangeal joint is a common injury and it needs to be operated on, otherwise the injured joint will be unstable and it will cause disability due to loss of pinch grip. A special absorbable device--self-reinforced poly-L-lactide mini tack--was used to stabilise this ruptured ligament. 140 patients were operated on because of this ligament injury. The preliminary results after six months' follow-up were good. Normal movement was regained in 118 out of 140 patients (84.3%) and stability in 138 patients (98.6%). Five reoperations (3.6%) were needed--one because of scar pain, one because of local infection nine months postoperatively, one because of instability and two because of late loosening of the tack six and nine months postoperatively. Overall the preliminary results were good. On the basis of these findings we consider this new absorbable fixation method suitable for clinical use for reinserting the ruptured ulnar collateral ligament of the first metacarpophalangeal joint of thumb.

Biodegradable wire fixation in olecranon and patella fractures combined with biodegradable screws or plugs and compared with metallic fixation.

The outcome of olecranon and patella fractures fixed with biodegradable implants (self-reinforced poly-L-lactide wire combined with self-reinforced polyglycolide screw or self-reinforced poly-L-lactide plug) or with metallic implants (tension band wiring, Kirschner wire and metallic cerclage wire) was compared in a prospective, randomized study. Twenty-five olecranon fractures (15 with biodegradable implants and 10 with metallic ones) and 10 patella fractures (6 with biodegradable implants and 4 with metallic ones) were treated. There were no differences between these methods in outcome. Olecranon and patella fractures can be treated using biodegradable implants successfully. The total expenses are lower because a second operation is not needed to remove the implants after fracture consolidation.

Arthrodesis in rheumatoid arthritis using absorbable screws and rods.

In this series absorbable fixation devices (screws and rods) made of self-reinforced poly-L-lactide (SR-PLLA) were used to stabilize arthrodesis in rheumatoid arthritis. These fixation devices have been used mainly in the fracture treatment or in the fixation of osteochondral lesions or osteotomies in hallux valgus operations. In arthrodesis of post-traumatic arthritis these devices have been used successfully. Fifty-three arthrodeses (18 in the wrist, 18 in the hand, 6 talocrural joint and 11 subtalar-calcaneocuboid-talonavicular joint) were performed for 47 patients using absorbable screws and rods between 1989 and 1994. Overall results in every group were good. There were 3 superficial infections and 2 nonunions (both talocrural arthrodesis). According to this study it seems that absorbable screws and rods are interesting alternative fixation devices in arthrodesis in rheumatoid arthritis.

Reinsertion of the ruptured ulnar collateral ligament of the metacarpophalangeal joint with an absorbable self-reinforced polylactide tack.

70 patients with total avulsion or rupture of the ulnar collateral ligament of the first metacarpophalangeal joint were treated surgically, using an absorbable self-reinforced poly-L-lactide mini-tack placed through the ligament and a channel in the base of the proximal phalanx. The device stabilized the joint immediately, and 69 ligaments remained stable at 6 months. The subjective result was good or satisfactory in 66 of the cases. One case needed further surgery for pain in the scar and another developed local infection 9 months post-operatively. On the basis of these findings, the new absorbable fixation method seems to be a suitable method for clinical use.

Beer as colon lavage preparation.

Six patients received beer preparation prior to double contrast barium enema. The beer group scored slightly better (though not statistically significantly) both in the cleanliness and in the mucosal coating of the bowel than the control group with standard preparation. The fluid balance was unaltered. The patients in the beer group felt surprisingly well, likely due to the good fluid and energy balance provided by the beer. The beer preparation could be used in cases, when the patients are ready to intake beer and want to maintain a good nutritional status.