Wrist Joint Skeletal Changes in Children With Transfusion-dependent Thalassemia.

BACKGROUND: Arthropathies and bone deformities are well known to occur in patients with thalassemia major and have been attributed to the disease or to its therapy. Before the advent of chelation therapy, these children developed widened diploic space and "hair-on-end" pattern in skull, "cobweb" pattern in the pelvis, and the lack of the normal concave outline in the long bones because of extensive marrow proliferation. After the introduction of iron-chelation therapy, these patients were noted to develop metaphyseal abnormalities and vertebral changes resembling spondylo-metaphyseal dysplasia. Only one study has shown some association of deferiprone (chelating agent) use with distal ulnar changes in these children. Our study was done to describe the skeletal changes and deformities in wrist joints of children with transfusion-dependent thalassemia and correlate them with age, mean pretransfusion hemoglobin level, mean serum ferritin level, and type and duration of chelation therapy in these children. METHODS: A total of 60 children with transfusion-dependent thalassemia from the thalassemia daycare center were examined. These children were divided into 3 groups on the basis of their age (group A: 2 to 6 y, group B: 6 to 10 y, and group C: 10 to 14 y). Detailed history, including treatment history, number of blood transfusions received over the last 1 year, clinical examination, and radiologic assessment of both forearm with wrists were done. RESULTS: The clinical and radiologic differences in radial and ulnar lengths increased significantly with the increasing age of these patients, the ulna being short. There was some correlation between increasing negative ulnar variance and distal radial articular angle with deferiprone consumption. CONCLUSION: Chelation therapy, particularly with deferiprone, may cause distal ulnar growth arrest causing ulnar shortening and progressive radial bowing in these children. LEVEL OF EVIDENCE: Level IV-case series.

Redox Regulation of Pro-IL-1ß Processing May Contribute to the Increased Severity of Serum-Induced Arthritis in NOX2-Deficient Mice.

AIMS: To elucidate the role of reactive oxygen species (ROS) in arthritis and to identify targets of arthritis treatment in conditions with different levels of oxidant stress. RESULTS: Through establishing an arthritis model by injecting arthritogenic serum into wild-type and NADPH oxidase 2 (NOX2)-deficient mice, we found that arthritis had a neutrophilic infiltrate and was more severe in Ncf1(-/-) mice, a mouse strain lacking the expression of the NCF1/p47(phox) component of NOX2. The levels of interleukin-1ß (IL-1ß) and IL-6 in inflamed joints were higher in Ncf1(-/-) than in controls. Antagonists of tumor necrosis factor-α (TNFα) and IL-1ß were equally effective in suppressing arthritis in wild-type mice, while IL-1ß blockade was more effective than TNFα blockade in Ncf1(-/-) mice. A treatment of caspase inhibitor and the combination treatment of a caspase inhibitor and a cathepsin inhibitor, but not a cathepsin inhibitor alone, suppressed arthritic severity in the wild-type mice, while a treatment of cathepsin inhibitor and the combination treatment of a caspase inhibitor and a cathepsin inhibitor, but not a caspase inhibitor alone, were effective in treating Ncf1(-/-) mice. Consistently, cathepsin B was found to proteolytically process pro-IL-1ß to its active form and this activity was suppressed by ROS. INNOVATION: This novel mechanism of a redox-mediated immune regulation of arthritis through leukocyte-produced ROS is important for devising an optimal treatment for patients with different levels of tissue ROS. CONCLUSION: Our results suggest that ROS act as a negative feedback to constrain IL-1ß-mediated inflammation, accounting for the more severe arthritis in the absence of NOX2.

Therapeutic effects of sunitinib, one of the anti-angiogenetic drugs, in a murine arthritis.

OBJECTIVES: The purpose of this study was to confirm the inhibitory effects of sunitinib, an angiogenesis inhibitor that targets tyrosine kinases of vascular endothelial growth factor receptor (VEGFR) family and platelet-derived growth factor receptor (PDGFR) family, on arthritis in mice with type II collagen-induced arthritis (CIA). METHODS: Sunitinib at a concentration of 30 or 60 mg/kg/day was intraperitoneally administered to mice with CIA. We compared the changes in arthritis score over time, pathological score, bone density, and microvascular density in synovial membrane between the vehicle and treatment groups. RESULTS: In the sunitinib-treated groups, the arthritis score decreased in a dose-dependent manner in comparison with that in the vehicle group. Furthermore, improvement in the pathological score, inhibitory tendency of loss in the bone density, and a decrease in the synovial microvascular density were also observed in the sunitinib-treated groups. CONCLUSIONS: Sunitinib remarkably inhibited arthritis, particularly synovial angiogenesis in a murine CIA model. This compound may be useful for treating arthritis.

[Case-control study on tibetan Baimai ointment (see symbol in text) for the treatment of wrist-dysfunction after distal radius fracture].

OBJECTIVE: To evaluate efficacy and safety of Baimai ointment (see symbol in text) in the treatment of wrist-dysfunction after distal radius fracture. METHODS: From April, 2011 to June, 2012, 43 patients with distal radius fracture were treated with plaster fixation. All the patients were divided into two group: test group and control group. Twenty-one patients in test group and 22 in control group, and the baseline was balance (P > 0.05). The 21 patients in test group were treated with Baimai ointment (see symbol in text), fomentation, functional exercises. The 22 patients in control group were treated with placebo, fomentation, functional exercises. Foment affected side wrist with wet towel in 20 min before medication, with the temperature between 50 degrees C and 60 degrees C. Smear drugs uniformly in range of 3 cm in the vicinity of palm stripes after drying (about 3 g) and take functional exercises for the activities of wrist and hand. Continuous follow the program per 8 hours once and follow-up for 8 weeks. The Wrist's pain was assessed with VAS. The wrist's activities were measured with the protractor of orthopedic. Measure The grip strength was measured with dynamometer. The wrist's function were assessed with the table of Cooney. RESULTS: The test group had a significantly better results than those of control group in the extent of wrist's pain throughout the treatment (P < 0.001), and grip strength on the 28th day and the 56th day (P < 0.05), and Cooney functional assessment on the 56th day (P < 0.05). Wrist's activities had no significane difference throughout the 8 weeks (P > 0.05). There were no drug adverse reactions occurred. CONCLUSION: Tibetan Baimai ointment (see symbol in text) has the treatment of wrist-dysfunction after distal radius fracture for external use, which can reduce the extent of wrist's pain, promote grip strength recovery in the middle and late of process, promote wrist's function recovery latterly, and safety for external use.

Joint inflammation and early degeneration induced by high-force reaching are attenuated by ibuprofen in an animal model of work-related musculoskeletal disorder.

We used our voluntary rat model of reaching and grasping to study the effect of performing a high-repetition and high-force (HRHF) task for 12 weeks on wrist joints. We also studied the effectiveness of ibuprofen, administered in the last 8 weeks, in attenuating HRHF-induced changes in these joints. With HRHF task performance, ED1+ and COX2+ cells were present in subchondral radius, carpal bones and synovium; IL-1alpha and TNF-alpha increased in distal radius/ulna/carpal bones; chondrocytes stained with Terminal deoxynucleotidyl Transferase- (TDT-) mediated dUTP-biotin nick end-labeling (TUNEL) increased in wrist articular cartilages; superficial structural changes (e.g., pannus) and reduced proteoglycan staining were observed in wrist articular cartilages. These changes were not present in normal controls or ibuprofen treated rats, although IL-1alpha was increased in reach limbs of trained controls. HRHF-induced increases in serum C1,2C (a biomarker of collagen I and II degradation), and the ratio of collagen degradation to synthesis (C1,2C/CPII; the latter a biomarker of collage type II synthesis) were also attenuated by ibuprofen. Thus, ibuprofen treatment was effective in attenuating HRHF-induced inflammation and early articular cartilage degeneration.

Efficacy of recombinant human alpha-L-iduronidase (laronidase) on restricted range of motion of upper extremities in mucopolysaccharidosis type I patients.

The aims of the study were to assess the effectiveness of enzyme replacement therapy (ERT) with laronidase on the range of motion (ROM) of upper extremities and influence on activities of daily living (ADLs) of patients with mucopolysaccharidosis type I (MPS I). The ROM of 17 patients with MPS I was followed from the first year of life until the introduction of ERT and after 52-208 weeks of treatment. In all patients (group 1, n = 10), passive ROM was assessed. In patients with Hurler/Scheie or Scheie phenotype (group 2, n = 7) both passive and active ROM, as well as daily life activities, were evaluated. Passive and active ROM was measured by a goniometer, while a health assessment questionnaire was used to assess activities of daily living. The data since the first months of life until the beginning of treatment were obtained by retrospective review of patients' charts. Restriction in ROM of the upper extremities of patients with MPS I was observed from the first year of life. These limitations intensified and became more severe with the patients' age, making patients' self-care more difficult or even impossible. Introduction of ERT led to slower progression of symptoms, especially in the passive range of motion in all patients. Additionally, patients with normal mental development, or only slightly delayed (group 2), who underwent active physical rehabilitation (including mobilisation of nerve system, passive techniques for joint mobility, active gymnastics for muscle power, as well as massage and the training of families for therapy at home) showed improvement in active movement followed by enhanced self-care.