Octacalcium Phosphate (OCP) Crystals Induce Synovial Inflammation and Cartilage

Introduction: The presence of intra-articular basic calcium phosphate (BCP) crystals, including OCP, carbonated-apatite, hydroxyapatite and tricalcium phosphate crystals, is associated with severe osteoarthritis and destructive arthropathies such as Milwaukee shoulder. Although BCP crystals displayed, in vitro, mitogenic, anabolic and catabolic responses, their intra-articular effect was never assessed.Objective: To determine the effects of OCP crystals in joints in vivo.Methods: OCP crystals (200 ug in 20 ml PBS) were injected into the right knee joint (the contra-lateral knee joint injected with 20 ul of PBS serving as a control) of wild-type mice treated or not by the IL1R antagonist Anakinra or mice deficient for the inflammasome proteins ASC and NALP3. 4 days and 17 days after crystal injection, mice were sacrificed and knee joints dissected. Histological scoring for synovial inflammation and characterisation of macrophages, neutrophils and T cells were performed. Technetium (Tc) uptake was measured at 6h, 1 and 4 days after OCP injection. Cartilage degradation was evaluated by Safranin O staining and VDIPEN immunohistochemistry. Intra-articular localisation of injected OCP crystals was evidenced by Von Kossa staining.Results: The intra-articular localisation of injected OCP crystals was evidenced by Von Kossa staining performed on non-decalcified samples embedded in methyl-metacrylate. Injection of OCP crystals into knee joints led at day 4 to an inflammatory response with intense macrophage staining and also some neutrophil recruitment in the synovial membrane. This synovitis was not accompanied by increased Tc uptake into the knee joint, Tc uptake being similar in OCP crystal injected knee or control knee at all time points investigated (6h, 1 day, 4 days). The histological modifications persisted over 17 days, with an additional fibrosis evidenced at this later time-point. The OCP crystal-induced synovitis was totally IL-1a and IL-1 independent as shown by the absence of inhibitory effects of anakinra injected into wild-type mice. Accordingly, OCP crystal-induced synovitis was similar in ASC-/- and NALP3-/- mice as no alterations of inflammation were demonstrated between these mice groups. Concerning cartilage matrix degradation, OCP crystals induced a strong breakdown of proteoglycans 4 and 17 days after injection, as measured by loss of red staining from Safranin O-stained sections of cartilage surfaces. In addition, we also measured advanced cartilage matrix destruction mediated by MMPs, as evidenced by VDIPEN staining of cartilage. OCP-mediated cartilage degradation was similar in all experimental conditions tested (WT+Anakinra, or ASC or NALP3 deficient mice).Conclusion: These data indicate in vivo that the intra-articular presence of OCP crystals is associated with cartilage destruction along with synovial inflammation. This is an interesting and new model of destructive arthropathy related to BCP crystals which will allow to assess new therapies in this disease.

Arthroskopie bei Hüftdysplasie [Arthroscopy in hip dysplasia]

[The causal treatment of a residual hip dysplasia consists of an acetabular reorientation osteotomy, the results of which, however, strongly depend on concomitant intra-articular lesions. The most important prognostic factor is the cartilage status. However, tears in the labrum and the ligament of the head of the femur may also be responsible for symptoms. Hip arthroscopy is a valuable tool for a precise diagnosis and simultaneous treatment of these lesions. However, as yet no results supporting this treatment algorithm have been published.]

CT arthrography of the glenohumeral joint: CT fluoroscopy versus conventional CT and fluoroscopy--comparison of image-guidance techniques.

PURPOSE: To compare examination time with radiologist time and to measure radiation dose of computed tomographic (CT) fluoroscopy, conventional CT, and conventional fluoroscopy as guiding modalities for shoulder CT arthrography. MATERIALS AND METHODS: Glenohumeral injection of contrast material for CT arthrography was performed in 64 consecutive patients (mean age, 32 years; age range, 16-74 years) and was guided with CT fluoroscopy (n = 28), conventional CT (n = 14), or conventional fluoroscopy (n = 22). Room times (arthrography, room change, CT, and total examination times) and radiologist times (time the radiologist spent in the fluoroscopy or CT room) were measured. One-way analysis of variance and Bonferroni-Dunn posthoc tests were performed for comparison of mean times. Mean effective radiation dose was calculated for each method with examination data, phantom measurements, and standard software. RESULTS: Mean total examination time was 28.0 minutes for CT fluoroscopy, 28.6 minutes for conventional CT, and 29.4 minutes for conventional fluoroscopy; mean radiologist time was 9.9 minutes, 10.5 minutes, and 9.0 minutes, respectively. These differences were not statistically significant. Mean effective radiation dose was 0.0015 mSv for conventional fluoroscopy (mean, nine sections), 0.22 mSv for CT fluoroscopy (120 kV; 50 mA; mean, 15 sections), and 0.96 mSv for conventional CT (140 kV; 240 mA; mean, six sections). Effective radiation dose can be reduced to 0.18 mSv for conventional CT by changing imaging parameters to 120 kV and 100 mA. Mean effective radiation dose of the diagnostic CT arthrographic examination (140 kV; 240 mA; mean, 25 sections) was 2.4 mSv. CONCLUSION: CT fluoroscopy and conventional CT are valuable alternative modalities for glenohumeral CT arthrography, as examination and radiologist times are not significantly different. CT guidance requires a greater radiation dose than does conventional fluoroscopy, but with adequate parameters CT guidance constitutes approximately 8% of the radiation dose.

Nouveautés en médecine interne générale ambulatoire (2) [General internal medicine: review of year 2009 from the ambulatory perspective (2)]

Despite two international studies, there is still no consensus concerning prostate cancer screening. The results of a meta-analysis are making us question our convictions concerning pneumococcal vaccination. The preoperative work-up of cataract surgery can be simplified. When describing the efficacy of a treatment to a patient, relative risks are better understood than absolute risks. For rotator cuff syndrome, intramuscular corticosteroid injections are as efficient as intra-articular injections. In patients prescribed clopidogrel, a proton pump inhibitor is not absolutely necessary. The arrival of a anticoagulant that does not need blood monitoring is an interesting option in atrial fibrillation.

Manifestations neurologiques des troubles musculosquelettiques [Neurological manifestations in musculoskeletal disorders].

Musculoskeletal disorders are a crossroad among diverse specialties: neurology, rehabilitation, orthopedics, occupational medicine and psycho-traumatology. They are integrated into occupational medicine and encompass overuse syndromes, repeated micro-trauma and focal compressive neuropathies linked with professional or sports' activity. Neurological manifestations are omnipresent. Yet, their importance is not always recognized despite frequent resort to neurologists specialized in peripheral nervous system disorders and neurophysiology, as well as, to behavioral cognition specialists. Therapeutic approaches require preventive and work organization measures, neurophysiologic investigations and imaging in expert hands, and conservative treatment with physiotherapy, with or without paraneural and intra-articular injections.

Wide resection of the lateral malleolus and adjacent tibial, talar and calcanear bones with ankle fusion and allograft reconstruction for an osteosarcoma.

Introduction: Primary bone sarcomas around the ankle are rare. Due to the proximity of neurovascular structures and limited soft tissue reserves, limb salvage is often not possible. Case report: A 19 yo male presented with pain and a progressive swelling of his ankle. X-rays revealed cortical erosions and an extensive periosteal reaction (sunburst) of the distal fibula. MRI showed a large mass of the fibula invading adjacent soft tissue. The lesion appeared close to the ankle joint, but with the articular cartilage as a barrier and without joint effusion. Core-needle biopsy revealed a high-grade chondroblastic osteosarcoma. No metastases were detected. After presentation at our multidisciplinary sarcoma board, the patient was subjected to neo-adjuvant chemotherapy (AOST 03-331). Without any sign of intra-articular contamination of the ankle joint, surgical treatment consisted of wide resection of the lateral malleolus including a large skin patch, the distal third of the fibula, the lateral surfaces of the tibia and talus as well as the insertion of the lateral ligament on the calcaneus. The distal parts of the anterior, peroneal, and posterior muscular compartments were resected en bloc with the tumor. The defect was reconstructed with tibio-talar and talo-calcanear fusion, bony allograft and a plate. Soft-tissue coverage was achieved with a free fascio-cutaneous flap from the controlateral thigh. Histological analysis revealed clear margins and 50% of tumor necrosis. The oncologic treatment was completed with adjuvant chemotherapy. Conclusion: Wide resection and reconstruction of the lateral malleolus is technically demanding but possible in selected cases. Despite some important functional loss, limb salvage is superior to an amputation.

Avulsion fracture of the peroneus longus tendon insertion at the base of the first metatarsal: report of a case.

Isolated avulsion fracture of the peroneus longus tendon insertion at the base of the first metatarsal is very rare. Similar to most avulsion fractures that result from excessive strain at a tendon or ligament insertion, this type of injury is caused by the strong tension exerted by the peroneus longus tendon. The mechanisms leading to this lesion and treatment options are not clearly defined. We present the case of an isolated minimally displaced intra-articular avulsion fracture at the plantar lateral base of the first metatarsal. Faced with a painful non-union following conservative treatment we considered excision of the bony fragment and first tarsometatarsal arthrodesis. This leads to a favourable functional outcome.

Pathogenic role of basic calcium phosphate crystals in destructive arthropathies.

BACKGROUND: basic calcium phosphate (BCP) crystals are commonly found in osteoarthritis (OA) and are associated with cartilage destruction. BCP crystals induce in vitro catabolic responses with the production of metalloproteases and inflammatory cytokines such as interleukin-1 (IL-1). In vivo, IL-1 production induced by BCP crystals is both dependant and independent of NLRP3 inflammasome. We aimed to clarify 1/ the role of BCP crystals in cartilage destruction and 2/ the role of IL-1 and NLRP3 inflammasome in cartilage degradation related to BCP crystals. METHODOLOGY PRINCIPAL FINDINGS: synovial membranes isolated from OA knees were analysed by alizarin Red and FTIR. Pyrogen free BCP crystals were injected into right knees of WT, NLRP3 -/-, ASC -/-, IL-1α -/- and IL-1β-/- mice and PBS was injected into left knees. To assess the role of IL-1, WT mice were treated by intra-peritoneal injections of anakinra, the IL-1Ra recombinant protein, or PBS. Articular destruction was studied at d4, d17 and d30 assessing synovial inflammation, proteoglycan loss and chondrocyte apoptosis. BCP crystals were frequently found in OA synovial membranes including low grade OA. BCP crystals injected into murine knee joints provoked synovial inflammation characterized by synovial macrophage infiltration that persisted at day 30, cartilage degradation as evidenced by loss of proteoglycan staining by Safranin-O and concomitant expression of VDIPEN epitopes, and increased chondrocyte apoptosis. BCP crystal-induced synovitis was totally independent of IL-1α and IL-1β signalling and no alterations of inflammation were observed in mice deficient for components of the NLRP3-inflammasome, IL-1α or IL-1β. Similarly, treatment with anakinra did not prevent BCP crystal effects. In vitro, BCP crystals elicited enhanced transcription of matrix degrading and pro-inflammatory genes in macrophages. CONCLUSIONS SIGNIFICANCE: intra-articular BCP crystals can elicit synovial inflammation and cartilage degradation suggesting that BCP crystals have a direct pathogenic role in OA. The effects are independent of IL-1 and NLRP3 inflammasome.

Avaliação de processos inflamatórios na articulação temporomandibular empregando leucócitos autólogos marcados com tecnécio-99m em modelo animal

OBJETIVO: O objetivo deste estudo foi identificar processos inflamatórios na articulação temporomandibular empregando leucócitos autólogos marcados com tecnécio-99m hexametilpropilenoaminooxima (99mTc-HMPAO). MATERIAIS E MÉTODOS: Foi utilizado um modelo experimental de indução de artrite na articulação temporomandibular de dez coelhos machos da raça Nova Zelândia, por meio da injeção intra-articular de ovalbumina na articulação temporomandibular esquerda de cada animal. Para controle, na articulação contralateral foi injetada solução salina. Após a marcação dos leucócitos com 99mTc-HMPAO e injeção endovenosa deste complexo nos coelhos, imagens cintilográficas foram obtidas. RESULTADOS: Observou-se captação aumentada dos 99mTc-HMPAO-leucócitos na articulação temporomandibular esquerda quando comparada à direita. A análise estatística foi realizada utilizando-se o teste não-paramétrico de Wilcoxon. Houve diferença estatisticamente significativa dos valores das contagens por minuto de radioatividade, relativos à articulação inflamada quando comparados aos valores obtidos na articulação contralateral (p = 0,0073). CONCLUSÃO: O método empregando leucócitos autólogos marcados com 99mTc-HMPAO é capaz de identificar focos inflamatórios de forma precoce e precisa, o que poderá contribuir na conduta terapêutica dos pacientes, antes que alterações estruturais sejam instaladas.

Hevosen osteoartriitin lääkehoito 1

Summary: Medical treatment of osteoarthritis in the horse. Part 1, intra-articular treatment

The Use of Radiostereometric Analysis in Fractures of the Distal Radius: From Phantom Models to Clinical Application

Radiostereometric analysis (RSA) is a highly accurate method for the measurement of in vivo micromotion of orthopaedic implants. Validation of the RSA method is a prerequisite for performing clinical RSA studies. Only a limited number of studies have utilised the RSA method in the evaluation of migration and inducible micromotion during fracture healing. Volar plate fixation of distal radial fractures has increased in popularity. There is still very little prospective randomised evidence supporting the use of these implants over other treatments. The aim of this study was to investigate the precision, accuracy, and feasibility of using RSA in the evaluation of healing in distal radius fractures treated with a volar fixed-angle plate. A physical phantom model was used to validate the RSA method for simple distal radius fractures. A computer simulation model was then used to validate the RSA method for more complex interfragmentary motion in intra-articular fractures. A separate pre-clinical investigation was performed in order to evaluate the possibility of using novel resorbable markers for RSA. Based on the validation studies, a prospective RSA cohort study of fifteen patients with plated AO type-C distal radius fractures with a 1-year follow-up was performed. RSA was shown to be highly accurate and precise in the measurement of fracture micromotion using both physical and computer simulated models of distal radius fractures. Resorbable RSA markers demonstrated potential for use in RSA. The RSA method was found to have a high clinical precision. The fractures underwent significant translational and rotational migration during the first two weeks after surgery, but not thereafter. Maximal grip caused significant translational and rotational interfragmentary micromotion. This inducible micromotion was detectable up to eighteen weeks, even after the achievement of radiographic union. The application of RSA in the measurement of fracture fragment migration and inducible interfragmentary micromotion in AO type-C distal radius fractures is feasible but technically demanding. RSA may be a unique tool in defining the progress of fracture union.

Avaliação da Velocidade Média na Aorta Torácica Descendente em Fetos com Anemia

Objetivo: verificar se existe correlação significativa entre a velocidade média na dopplerfluxometria da artéria aorta torácica descendente e o grau de anemia fetal. Métodos: estudo prospectivo, transversal, no qual foram analisados 66 fetos de gestantes isoimunizadas, em que se realizou a cordocentese para a realização de transfusões intra-uterinas pela via intravascular (66,7%). Nos fetos que foram submetidos à transfusão intra-uterina pela via intraperitoneal, ou naqueles casos em que não houve necessidade de tratamento intra-uterino (33,3%), a determinação da concentração de hemoglobina do cordão foi realizada pela punção do cordão umbilical, no momento da interrupção da gestação. Neste grupo de fetos estudados, foi realizado exame dopplerfluxométrico da artéria aorta torácica descendente, sendo calculada a velocidade média de fluxo. Foi realizado estudo de associação entre as variáveis. Foram também calculados os valores de sensibilidade, especificidade, valores preditivos positivo e negativo. Resultados: observou-se correlação significativa e inversa entre a velocidade média na artéria aorta torácica descendente e o nível de hemoglobina fetal. A velocidade média na dopplerfluxometria da artéria aorta torácica descendente apresentou sensibilidade de 47,5% para anemia fetal moderada (Hg<10 g/dL), com o teste exato de Fisher apresentando valor de p<0,01, e de 54,5% para anemia fetal grave (Hg<7,0 g/dL), com um valor de p=0,01. Conclusões: houve associação significativa entre a velocidade média na aorta torácica descendente e o grau de diagnóstico de anemia fetal.

Rastreamento e diagnóstico ecocardiográfico das arritmias e cardiopatias congênitas fetais

OBJETIVO: analisar os resultados obtidos em programa de rastreamento e diagnóstico de arritmias e cardiopatias congênitas centrado em uma unidade terciária e determinar a importância do diagnóstico precoce na evolução fetal e neonatal. MÉTODOS: foram analisados os resultados da avaliação cardíaca fetal efetuada em 1159 gestantes em dois níveis diferentes. Nível I: uso da ultra-sonografia morfológica com o objetivo de rastrear a presença de alteração cardíaca, sem estabelecer um diagnóstico diferencial. Nível II: por ecocardiograma fetal com o objetivo de diagnosticar as cardiopatias fetais existentes. Os resultados da detecção de arritmias bem como da avaliação das alterações estruturais foram comparados, sendo estabelecidas a sensibilidade e a especificidade para ambos os níveis no pré-natal, ao exame pós-natal ou à necropsia. A concordância entre ambos os níveis foi calculada pelo índice kappa. RESULTADOS: as arritmias detectadas no nível I foram confirmadas em todos os casos e não houve falso-negativos, sendo que em cinco pacientes houve necessidade de tratamento intra-útero. A detecção das alterações estruturais obtidas no nível I teve sensibilidade de 72% e especificidade de 98%, com 28% de falso-positivos. No nível II estes parâmetros foram, respectivamente, de 100 e 99%. De acordo com o coeficiente kappa de 57%, um grau de concordância de categoria moderada foi observado entre ambos os níveis. Das cardiopatias congênitas da nossa série 51% necessitaram intervenção farmacológica ou invasiva no período neonatal. CONCLUSÃO: o estudo ultra-sonográfico obstétrico é fundamental no rastreamento das alterações cardíacas fetais. O ecocardiograma fetal apresentou alto índice de sensibilidade e especificidade no diagnóstico das arritmias e cardiopatias congênitas, possibilitando o tratamento precoce das alterações graves.

Loss of Ovarian Function Results in Increased Loss of Skeletal Muscle in Arthritic Rats

Objective We studied the effects of loss of ovarian function (ovariectomy) onmuscle mass of gastrocnemius and themRNA levels of IGF-1, atrogin-1, MuRF-1, andmyostatin in an experimental model of rheumatoid arthritis in rats. Methods We randomly allocated 24 female Wistar rats (9 weeks, 195.3±17.4 grams) into four groups: control (CT-Sham; n = 6); rheumatoid arthritis (RA; n = 6); ovariectomy without rheumatoid arthritis (OV; n = 6); ovariectomy with rheumatoid arthritis (RAOV; n = 6). We performed the ovariectomy (OV and RAOV) or Sham (CTSham or RA) procedures at the same time, fifteen days before the rheumatoid arthritis induction. The RA and RAOV groups were immunized and then were injected with Met- BSA in the tibiotarsal joint. After 15 days of intra-articular injections the animals were euthanized. We evaluated the external manifestations of rheumatoid arthritis (perimeter joint) as well as animal weight, and food intake throughout the study. We also analyzed the cross-sectional areas (CSA) of gastrocnemius muscle fibers in 200 fibers (H&E method). In the gastrocnemius muscle, we analyzed mRNA expression by quantitative real time PCR followed by the Livak method (ΔΔCT). Results The rheumatoid arthritis induced reduction in CSA of gastrocnemius muscle fibers. The RAOV group showed a lower CSA of gastrocnemius muscle fibers compared to RA and CT-Sham groups. Skeletal muscle IGF-1 mRNA increased in arthritics and ovariectomized rats. The increased IGF-1 mRNA was higher in OV groups than in the RA and RAOV groups. Antrogin-1 mRNA also increased in the gastrocnemius muscle of arthritic and ovariectomized rats. However, the increased atrogin-1 mRNA was higher in RAOV groups than in the RA and OV groups. Gastrocnemius muscle MuRF-1 mRNA increased in the OVand RAOVgroups, but not in the RA and Shamgroups. However, the RAOV group showed higher MuRF-1 mRNA than the OV group. The myostatin gene expression was similar in all groups. Conclusion Loss of ovarian function results in increased loss of skeletal musclerelated ubiquitin ligases atrogin-1 and MuRF-1 in arthritic rats.

Contribuição do contraste negativo na artrografia tomográfica do joelho normal de cães

A ruptura do ligamento cruzado cranial é uma das causas mais comuns de claudicação do membro pélvico de cães. A radiografia e a ultrassonografia são métodos de diagnóstico frequentemente utilizados na rotina clínica de pequenos animais, porém a tomografia computadorizada é uma modalidade de imagem ainda pouco estudada para avaliar a articulação do joelho de cães. O presente trabalho teve por objetivo avaliar a contribuição do contraste negativo na artrografia tomográfica do joelho normal de cães, para visibilizar as estruturas intra-articulares e padronizar o uso desse contraste na articulação. Foram utilizados 24 membros pélvicos de cães de raças variadas, selecionados pela ausência de histórico de doença articular prévia do joelho e por apresentarem exames radiográficos, ultrassonográficos e macroscópicos normais. O experimento foi delineado em dois grupos, sendo o grupo I constituído de animais com peso até 20 kg e grupo II acima de 20 kg. Foram feitos cortes tomográficos com o membro flexionado e estendido. A quantidade média de ar empregada para a distensão da cápsula articular foi de 49 ml para o Grupo I e de 81 ml para o Grupo II. Utilizou-se um tubo de látex na porção distal à articulação do joelho para reduzir o escape de ar pelo tendão extensor digital profundo, que possui comunicação intra-articular. Foi possível visibilizar pela imagem tomográfica, em todas as articulações, as seguintes estruturas: ligamento cruzado cranial e caudal, meniscos medial e lateral, ligamento patelar, ligamentos colaterais e cápsula articular. Desta forma, o contraste negativo se mostrou uma alternativa eficaz para auxiliar a identificação das estruturas anatômicas do joelho na artrografia tomográfica.