Dominique Le Nen

Characterization and Functional Consequences of Underexpression of Clusterin in Rheumatoid Arthritis

We previously compared by microarray analysis gene expression in rheumatoid arthritis (RA) and osteoarthritis (OA) tissues. Among the set of genes identified as a molecular signature of RA, clusterin (clu) was one of the most differentially expressed. In the present study we sought to assess the expression and the role of CLU (mRNA and protein) in the affected joints and in cultured fibroblast-like synoviocytes (FLS) and to determine its functional role. Quantitative RT-PCR, Northern blot, in situ hybridization, immunohistochemistry, and Western blot were used to specify and quantify the expression of CLU in ex vivo synovial tissue. In synovial tissue, the protein was predominantly expressed by synoviocytes and it was detected in synovial fluids. Both full-length and spliced isoform CLU mRNA levels of expression were lower in RA tissues compared with OA and healthy synovium. In synovium and in cultured FLS, the overexpression of CLU concerned all protein isoforms in OA whereas in RA, the intracellular forms of the protein were barely detectable. Transgenic overexpression of CLU in RA FLS promoted apoptosis within 24 h. We observed that CLU knockdown with small interfering RNA promoted IL-6 and IL-8 production. CLU interacted with phosphorylated IκBα. Differential expression of CLU by OA and RA FLS appeared to be an intrinsic property of the cells. Expression of intracellular isoforms of CLU is differentially regulated between OA and RA. We propose that in RA joints, high levels of extracellular CLU and low expression of intracellular CLU may enhance NF-κB activation and survival of the synoviocytes.

Detection of occult wrist fractures by quantitative radioscintigraphy: a prospective study on selected patients.

ObjectiveTo determine the value of quantitative radioscintigraphy (QRS) in the diagnosis of wrist trauma occult fractures. PurposeBecause of the risk of non-union, the diagnosis of wrist fractures, including scaphoid fractures, is essential but remains difficult despite many imaging modalities. The aim of the study was to assess the benefits of QRS in the diagnosis of occult post-trauma wrist fractures. MethodsThis prospective study included all patients presenting at the orthopaedic department at Brest University Hospital for wrist pain after trauma with initial normal plain radiographs. Patients with normal radiographs but strongly suspected of fracture underwent QRS consisting of three-phase bone scintigraphy with quantitative analysis. When a fracture was suspected the radiograph and scintigraphy were fused to precisely locate the fracture if the index was higher than 2. If the index was lower than 1.9, fracture was excluded. Between these two indices, other investigations, such as magnetic resonance imaging, were performed. All patients were followed for at least 3 months and reviewed by the same surgeon. Patients underwent a physical examination and possibly other investigations. ResultsFrom April 2006 to July 2008, 87 patients were enrolled (34 women, 53 men; median age 29 years; range, 15–87 years). Among the 46 pathologic bone scintigrams, 55 occult fractures were highlighted. At follow-up, none presented non-union. One had an undetermined QRS. Among the 40 negative results for QRS at follow-up, only one had a non-union. Sensitivity and negative predictive value were 97 and 98%, respectively for carpal fractures. ConclusionThis study highlights the benefit of QRS, which allows the detection of most occult carpal fractures and reduces the risks of complications such as pseudoarthritis.

Lumbo-sacral malformations and spina bifida occulta in medieval skeletons from Brittany

IntroductionCompared with the other French regions, the incidence of neural tube defects is raised in Brittany. It can be explained by the Celtic origin of the Britton people, who migrated from Great Britain in the High Middle Ages. Notwithstanding, there are no historical or archeological evidences of the occurrence of these pathological conditions in medieval Brittany.Materials and methodsWe investigated the incidence of lumbo-sacral malformations on the skeletal remains of 30 individuals excavated from the necropolis of Saint-Urnel (southwest Brittany).ResultsWe found out several anatomical variations among five specimens, three of which had spinal dysraphism involving the sacrum.ConclusionOur results enrich the very few paleopathological data about spinal dysraphism, from the Hippocratic Corpus to the first description of Spina Bifida in sixteenth century. But, their interpretation remains delicate until the same genetic factors are shown in the etiology of both open and closed spinal dysraphism.

Fibro-osseous pseudotumour of the digit in a patient with rheumatoid arthritis

A 61-year-old woman had been treated with methotrexate for a seropositive and erosive rheumatoid arthritis since 2001. In November 2011 she developed a painless inflammatory tumefaction of the right index finger. She did not report any previous trauma or wound. Standard biology and initial X-rays were normal. Ultrasound analysis and MRI (Fig. 1A) showed inflammatory soft tissue oedema and bone marrow oedema of the middle phalanx. A profound skin biopsy was performed. Bacteriological investigations were negative. Histology showed nonspecific oedema of soft tissues without inflammatory infiltrate. One month later the volume of the tumefaction increased (Fig. 1B). A control X-ray showed periosteal calcifications around the middle phalanx (Fig. 1C). A surgical bone biopsy was performed, but histology was again non-specific, showing non-inflammatory necrotic and fragmentated bone. Two months later, in the absence of an aetiological diagnosis, amputation of the finger was carried out. Definitive histology (Fig. 1D) described a periosteal centrifuge neo-osteogenesis consisting of focal irregular trabeculae with osteoid formation and osteoblastic rimming, evocative of fibro-osseous pseudotumour. This is a rare, non-malignant heterotopic ossifying lesion involving the subcutaneous tissues of the digits. The treatment of choice is, when possible, conservative complete excision of the lesion, leading most of the time to complete recovery [1].

Arthroscopic arthrodesis of the shoulder in brachial plexus palsy.

BACKGROUND Shoulder arthroscopic arthrodesis is an uncommon and non-standardized procedure. Results are poorly evaluated. We describe the findings in 8 patients who underwent shoulder arthroscopic arthrodesis for brachial plexus injury. METHODS The humeral head and glenoid were excised through standard arthroscopic portals. A Hoffmann external fixator and cannulated screws were used to stabilize the shoulder. Standard clinical assessment and radiographic evaluation were performed each month until bony fusion occurred. With a mean follow-up of 28 months, functional evaluation included pain level (on a 0- to 10-mm visual analog scale); American Shoulder and Elbow Surgeons index; Disabilities of the Arm, Shoulder and Hand score; and Simple Shoulder Test score. Mobility was systematically investigated. Blood loss was assessed by measuring hematocrit proportion. RESULTS Glenohumeral fusion was achieved in all 8 patients. The mean time to arthrodesis was 3 months (range, 2-8 months). At last follow-up, the mean pain level was 1 (range, 0-4); the mean American Shoulder and Elbow Surgeons score was 69; the mean Disabilities of the Arm, Shoulder and Hand score was 36; and the mean Simple Shoulder Test score was 4. Mean active flexion and abduction were 80° (range, 60°-90°) and 59° (range, 40°-80°), respectively. Mean blood loss during the perioperative period was 432 mL (range, 246-792 mL). We observed one superficial wound infection and one migration of an acromiohumeral screw. These complications did not compromise the final results. CONCLUSIONS Arthroscopic arthrodesis of the shoulder can be a reliable procedure and associated with a low rate of complications.

Transseptal dorsal approaches to the wrist

BackgroundThe dorsal approach to the wrist is the exposure of choice for most of the surgical procedures on the radiocarpal and intercarpal joints. Contrary to the volar approach, it encounters neither the main arteries nor the motor nerve branch. However, the dorsal approach goes necessarily through the extensor retinaculum. We describe two transseptal dorsal approaches that pass through the extensor retinaculum in the thickness of a septum between two compartments. A virtual space was developed beneath the infratendinous retinaculum (which is a deep layer covering the floor of the extensor compartments) to expose the periosteum, the ligaments and the joint capsule without opening the extensor compartments.MethodsTwenty cadaveric wrists have been dissected to study the feasibility of the two transseptal approaches. Ten wrists were exposed through a 3–4 transseptal approach, passing through the extensor retinaculum in the thickness of the septum between the third and fourth compartments. Ten wrists were exposed through a 4–5 transseptal approach, passing through the extensor retinaculum in the thickness of the septum between the fourth and fifth compartments. The extent of violations of extensor compartments and joint capsule, and the exposed anatomical structures were noted. At the end of each dissection, the whole extensor system was outrightly removed for histological study.ResultsThe feasibility of the transseptal approaches was demonstrated for all the dissected wrists. The dissection plane beneath the infratendinous retinaculum was macroscopically and microscopically highlighted.ConclusionsThe transseptal approaches provide a good exposure to the dorsal side of the wrist joint, without opening the extensor tendon compartments.

De la main

Les planches consacrees a la main sont particulierement somptueuses et nous font entrer, avec les yeux et la main de Leonard, dans les profondeurs d’une anatomie qu’aucun homme n’avait jusqu’alors aussi bien analysee.

De la fonction de préhension

Dans l’esprit de Leonard, la main, le mouvement de prono-supination et la rotation de l’epaule semblent bien constituer une entite faite pour la prehension. Tout mouvement du membre superieur a donc pour objectif la presentation optimale de la main dans le but de l’amener au geste adapte, qu’il soit conscient ou non. De meme le membre inferieur est acquis a la fonction de locomotion qui requiert la propulsion du pied, bien illustree par Leonard dans un schema mecanique du passage du pas avec la contraction du puissant triceps sural16, schema o combien dynamique17.

Fracturas, esguinces y luxaciones de la mano y los dedos

Resumen Las fracturas, esguinces y luxaciones de la mano y de los dedos son producto de traumatismos muy diversos y son de gran polimorfismo clinico, ya que pueden afectar a todas las estructuras oseas y a todas las articulaciones. Cada etapa del acto medico es fundamental, incluso si su aparente benignidad suele hacer pasar por alto dicha actitud: etapa diagnostica, mediante la exploracion fisica y radiografica; etapa terapeutica, con la eleccion del tratamiento mas adecuado y asociando, en todos los casos y tan pronto como sea posible, la movilizacion de las cadenas digitales; control regular con el fin de detectar las posibles complicaciones, en particular un desplazamiento secundario, asi como el de comprobar el correcto desarrollo de la rehabilitacion. En el tratamiento de cualquier lesion osea o articular ?no radica siempre el objetivo final en preservar la anatomia y dar prioridad a la estabilidad y movilizacion de las cadenas digitales? La posible evolucion hacia secuelas funcionales mayores como la mano dolorosa, inestable o rigida, con su inevitable repercusion socioeconomica, debe ser una preocupacion constante desde el momento en que se asiste a un traumatismo de la mano y de los dedos.