[Validation of the French version of the self-evaluation of negative symptoms (SNS)]. / Validation de la version française de l'échelle autoévaluation des symptômes négatifs (SNS).

INTRODUCTION: Schizophrenia is a disorder affecting 1% of the population and is associated with severe functional impairment. Negative symptoms are responsible for the majority of this impairment, and many patients with schizophrenia have negative symptoms. However, their evaluation is still a challenge. Thus, standardized assessments are needed to facilitate identification of these symptoms. Many tools have been developed, but most are based on observer ratings. Self-evaluation can provide an additional outcome measure and allow patients to be more engaged in their treatment. The Self-evaluation of Negative Symptoms (SNS) has been developed recently. This is a remarkably understandable instrument for patients with schizophrenia as it allows them to readily complete it without assistance, providing information with respect to their own perception of negative symptoms. The SNS is a self-assessment that permits patients to evaluate themselves in 5 dimensions of negative symptoms. This validation study for the SNS revealed good psychometric properties alongside satisfactory acceptance by patients. AIM: This study was to confirm the validation of the French version of the self-evaluation of negative symptoms (SNS). METHODS: Patients with schizophrenia or schizoaffective disorder according to the DSM-IV-R, with a stable regimen of anti-psychotic drugs for the last two months, aged more than 18 years old were eligible for the study. Symptoms were rated using the SNS, the Scale for the Assessment of Negative Symptoms (SANS), the Calgary Depression Scale for Schizophrenics (CDSS), the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression and Parkinsonism. Patients were asked to fulfill the SNS twice, 6 weeks apart. RESULTS: Sixty patients were evaluated. Cronbach's coefficient (α=0.8) showed good internal consistency. The SNS significantly correlated with the SANS (r=0.6), the negative sub-score of the BPRS (r=0.6) and the Clinician Global Impression on the severity of negative symptoms (r=0.7). SNS scores did not correlate with level of insight (r=0.08) or Brief Psychiatric Rating Scale positive sub-scores (r=0.2). SNS scores correlated with CDSS scores. However, we did not find correlation between the first item of the CDSS which evaluates depression and the "diminished emotional range" sub-score of SNS. The test-retest of SNS revealed no changes of scores at two evaluations 6 weeks apart. CONCLUSION: The acceptance by patients of the SNS was excellent. The French version of the SNS demonstrated a good internal consistency, good convergent validity and good discriminant validity. The study demonstrates the ability of patients with schizophrenia to accurately report their own experiences. Self-assessments of negative symptoms should be more widely employed in clinical practice because they may allow patients with schizophrenia to develop appropriate coping strategies.

Distinct expression of interleukin (IL)-36α, ß and γ, their antagonist IL-36Ra and IL-38 in psoriasis, rheumatoid arthritis and Crohn's disease.

Interleukin (IL)-36α, IL-36ß and IL-36γ are expressed highly in skin and are involved in the pathogenesis of psoriasis, while the antagonists IL-36Ra or IL-38, another potential IL-36 inhibitor, limit uncontrolled inflammation. The expression and role of IL-36 cytokines in rheumatoid arthritis (RA) and Crohn's disease (CD) is currently debated. Here, we observed that during imiquimod-induced mouse skin inflammation and in human psoriasis, expression of IL-36α, γ and IL-36Ra, but not IL-36ß and IL-38 mRNA, was induced and correlated with IL-1ß and T helper type 17 (Th17) cytokines (IL-17A, IL-22, IL-23, CCL20). In mice with collagen-induced arthritis and in the synovium of patients with RA, IL-36α, ß, γ, IL-36Ra and IL-38 were all elevated and correlated with IL-1ß, CCL3, CCL4 and macrophage colony-stimulating factor (M-CSF), but not with Th17 cytokines. In the colon of mice with dextran sulphate sodium-induced colitis and in patients with CD, only IL-36α, γ and IL-38 were induced at relatively low levels and correlated with IL-1ß and IL-17A. We suggest that only a minor subgroup of patients with RA (17-29%) or CD (25%) had an elevated IL-36 agonists/antagonists ratio, versus 93% of patients with psoriasis. By immunohistochemistry, IL-36 cytokines were produced by various cell types in skin, synovium and colonic mucosa such as keratinocytes, CD68⁺ macrophages, dendritic/Langerhans cells and CD79α⁺ plasma cells. In primary cultures of monocytes or inflammatory macrophages (M1), IL-36ß and IL-36Ra were produced constitutively, but IL-36α, γ and IL-38 were produced after lipopolysaccharide stimulation. These distinct expression profiles may help to explain why only subgroups of RA and CD patients have a potentially elevated IL-36 agonists/antagonists ratio.

Interleukin 34 expression is associated with synovitis severity in rheumatoid arthritis patients.

OBJECTIVES: Interleukin (IL) 34 is a new cytokine implicated in macrophage differentiation and osteoclastogenesis. This study assessed IL-34 expression in the tissue of patients with rheumatoid arthritis (RA). METHODS: Immunohistochemistry was performed in synovial biopsies from patients with RA (n=20), osteoarthritis (n=3) or other inflammatory arthritis (n=4). IL-34 was detected in the synovial fluid by ELISA and its messenger RNA expression was studied by quantitative PCR in rheumatoid synovial fibroblasts after stimulation by tumour necrosis factor α (TNFα) and IL-1ß. Wild-type, jnk1(-/-)-jnk2(-/-) and nemo(-/-) murine fibroblasts and pharmacological inhibition were used to determine the involvement of nuclear factor kappa B (NF-κB) and JNK in that effect. RESULTS: IL-34 was expressed in 24/27 biopsies, with three samples from RA patients being negative. A significant association was found between IL-34 expression and synovitis severity. Levels of IL-34 and the total leucocyte count in synovial fluid were correlated. TNFα and IL-1ß stimulated IL-34 expression by synovial fibroblasts in a dose/time-dependent manner through the NF-κB and JNK pathway. CONCLUSION: This work for the first time identifies IL-34 expression in the synovial tissue of patients with arthritis. This cytokine, as a downstream effector of TNFα and IL-1ß, may contribute to inflammation and bone erosions in RA.

Tolerance and effect of sodium thiosulfate in calcific tendinitis of the rotator cuff.

BACKGROUND: Calcific tendinitis of the rotator cuff is one of the most common causes of shoulder pain. Ultrasound-guided percutaneous lavage of calcific tendinopathy is performed when conservative treatments have failed. Sodium thiosulfate (STS) has recently been used with success in the treatment of tumoral calcinosis. The goal of this phase II study was to assess the tolerance and the feasibility of STS lavage of calcific tendinopathy. METHODS: We included patient with type hard calcifications. Patients were treated with puncture and lavage followed by injection of STS in the calcification. VAS pain at rest and during activities, ultrasound, and X-ray were evaluated at 1 week and 1 and 3 months. RESULTS: Seventeen patients were included. Baseline VAS at rest and during daily activities was a mean 40.2 ± 25.9 and 65.5 ± 21.6 respectively. All patients underwent the entire procedure with no adverse event. Calcium backflow could be obtained in 15 patients (88.2%). Five patients (30%) had more than 50% decrease of their calcific deposit size at 1 month and 8 (47%) patients at 3 months. VAS pain during activities and at rest decreased significantly at 3 months (p = 0.0004; p = 0.001). Efficacy would be demonstrated if 60% of the patients had more than 50% decrease size of their calcification CONCLUSION: Overall, STS was well tolerated with no side effect occurring during the procedure and the follow-up. However, no significant effect on calcium disappearance could be demonstrated compared with what is expected without STS. New studies using larger volume and repeated injections of STS are now needed. CLINICAL TRIAL REGISTRATION NUMBER: NCT02538939Key Points• Lavage of calcific tendinopathy of the rotator cuff with sodium thiosulfate is feasible• No adverse events have been observed after or in the 3 months after the procedure• We could not demonstrate that sodium thiosulfate increases the chance of calcium disappearance• New studies using larger volume and repeated injections of STS are needed to further explore the interest of sodium thiosulfate in the treatment of calcific tendinopathy.

US-guided temporomandibular joint injection: Validation of an in-plane longitudinal approach.

Ultrasonography of the temporomandibular joint is a non-invasive imaging technic, easy to perform in daily practice. It can be used for diagnosis and to guide intra-articular injections. The objective was to validate a longitudinal in-plane US injection approach of the joint and assess its accuracy. We performed a study in 13 non-embalmed cadavers. The injection was done under real-time US guidance using a needle inserted in-plane with an angulation of 30°and positioned under the capsule until the injection was feasible without resistance. The intra-articular injection was successful in all cases and confirmed by a liquid backflow in 96% of cases. The median duration between skin puncture and the intra-articular injection was 23 seconds. Our technique allows a direct visualization of the needle throughout its course to the joint with a high accuracy. Other studies will be needed to confirm its feasibility and usefulness in patients with TMJ disorders.

[Sciatica with motor loss revealing meningoradiculitis due to varicella-zoster virus]. / Sciatique déficitaire révélant une méningoradiculite attachée au virus zona-varicelle.

Herpes zoster is a disease which occurs secondary to the reactivation of varicella-zoster virus. Motor involvement in acute herpes zoster is rare. We report a case of sciatica L5 due to herpes zoster infection with motor loss. Typical skin lesions occurred one week before the sciatica. Radiological finding did not explain the paresis. The diagnosis of zoster sciatica with motor involvement was suspected. Serological tests and cerebrospinal fluid examination established the diagnosis. The antiviral and physical treatment was conducted in order to improve functional outcome.

DU145 human prostate cancer cells express functional receptor activator of NFkappaB: new insights in the prostate cancer bone metastasis process.

Prostate cancer metastases to bone are observed in around 80% of prostate cancer patients and represent the most critical complication of advanced prostate cancer, frequently resulting in significant morbidity and mortality. As the underlying mechanisms are not fully characterized, understanding the biological mechanisms that govern prostate cancer metastases to bone at the molecular level should lead to the determination of new potential therapeutic targets. Receptor activator of NFkappaB ligand (RANKL)/RANK/Osteoprotegerin (OPG) are the key regulators of bone metabolism both in normal and pathological condition, including prostate cancer bone metastases. In the present study, we demonstrated that human prostate cancer cell lines, DU145 and PC3 express biologically functional RANK. Indeed, soluble human RANKL (shRANKL, 100 ng/ml) treatment induced ERK 1/2, p38 and IkappaB phosphorylations in these cells. shRANKL administration also promoted DU145 and PC3 prostate cancer cell invasion in vitro. Whereas human OPG (hOPG) administration alone (100 ng/ml) had no marked effect, combined association of both agents abolished the RANKL-induced DU145 cell invasion. As RANKL had no direct effect on DU145 cell proliferation, the observed effects were indeed related to RANKL-induced cell migration. DU145 human prostate cancer cells promoted osteoclastogenesis of osteoclast precursors generated from mouse bone marrow. Moreover, DU145 cells produced soluble factor(s) that up-regulate the proliferation of MC3T3-E1 pre-osteoblasts through the activation of the ERK 1/2 and STAT3 signal transduction pathways. This stimulation of pre-osteoblast proliferation resulted in an increased local RANKL expression that can activate both osteoclasts/osteoclast precursors and prostate cancer cells, thus facilitating prostate cancer metastasis development in bone. We confirm that RANKL is a factor that facilitates metastasis to bone by acting as an activator of both osteoclasts and RANK-positive prostate cancer cells in our model. Furthermore, the present study provides the evidence that blocking RANKL-RANK interaction offer new therapeutic approach not only at the level of bone resorbing cells, but also by interfering with RANK-positive prostate cancer cells in the prostate cancer bone metastasis development.

Presence of an intracompartmental septum detected by ultrasound is associated with the failure of ultrasound-guided steroid injection in de Quervain's syndrome.

UNLABELLED: The purpose of this study was to find clinical or ultrasound characteristics that might predict the failure of conservative treatment in de Quervain's syndrome. A total of 42 ultrasound-guided injections have been performed in 41 patients after clinical and ultrasound examination. Patients were immobilized for 3 weeks with a spica splint cast, and clinically evaluated at 3 and 6 weeks and by phone call at the end of the study. Ultrasound showed a septum between the tendons of the first comportment in 34% of the wrists. At last follow-up (mean 15.6 months after the injection) ten patients (24%) had undergone surgery. When comparing ultrasound and clinical characteristics of the operated and non-operated wrists, we found that patients with a high baseline visual analogue scale, with all positive clinical tests and with a persistent intracompartmental septum, had a significantly higher risk of failure following conservative treatment. LEVEL OF EVIDENCE: III.

[Three cases of Jaccoud's arthropathy during systemic sclerosis]. / Trois observations de rhumatisme de Jaccoud au cours de la sclérodermie systémique.

INTRODUCTION: Jaccoud's arthropathy (JA) is a chronic and non-erosive deforming arthropathy, usually affecting the hands. JA pathophysiology is poorly known but involves periarticular structures such as tendons and the joint capsule. JA is associated with various conditions including the connective tissue disease, especially systemic lupus erythematosis. JA has been rarely described and studied in systemic sclerosis. CASE REPORTS: We report the clinical histories of 3 patients with systemic sclerosis (ScS) who developed JA. One patient had a systemic limited disease and the 2 others a cutaneous limited disease ; mean age of the patients was 79.3 years. Systemic sclerosis was diagnosed respectively 19, 1 and 21 years prior to the development of JA. One of the 3 patients had a past clinical history of discoid lupus. For 1 out of the 3 patients, JA appeared whereas the ScS was completely stable. The disease was still active in the 2 remaining patients, with concurrent pulmonary hypertension diagnosis. Deformities increased during years (Z thumbs, ulnar deviation), leading to mild to severe disability. No benefit from either prednisone (n=2) or a combination of prednisone and methotrexate (n=1) was obtained. CONCLUSION: We described 3 cases of Jaccoud's arthropathy among our scleroderma cohort of 296 patients (1%). This arthropathy worsens hand functional disability. Its pathophysiology is unknown and optimal therapeutic approach remains to establish.

[Triangular reflections on manic-depressive disorder. Apropos of 72 cases]. / Réflexions triangulaires sur la psychose maniaco-dépressive. A propos de 72 cas.

In 72 cases of unipolarity or bipolarity depression followed at least three years the subsequent elements are questioned. What is the proportion of the different diagnostic types and what have been the most frequent life events of the first access, deaths, occupational and emotional failures, pregnancy, births, etc? In this population of patients between 23 and 80 years old reluctance or ignorance of the life events are important. We also investigated the level of our patients socio-professional insertion. As for the hetero ou auto aggressive acting out we tried to quantify them according to the chosen classification and the therapy followed by the patients of this group. In the hypothesis of a possible link with the hospital management evaluation and computer program we have briefly analyzed the incidence of lithium therapy on the number of hospitalisation days, without being able to draw a final conclusion as to the interest of this therapy in this very specific issue.

[Ultrasonography in chronic inflammatory rheumatic and connective tissue disorders]. / Intérêt de l'échographie ostéo-articulaire dans les rhumatismes inflammatoires chroniques et les connectivites.

Musculoskeletal ultrasonography is now widely used by almost all rheumatologists thanks to an improvement in the quality of ultrasound unit and probe and to the systematic teaching of this imaging technique to the rheumatology fellows. Applications have broadened from the study of degenerative and mechanical diseases to inflammatory rheumatic diseases. Ultrasound is more sensitive than clinical examination. Power Doppler allows the direct visualisation of inflammation within the tissues. Finally, it is a prognostic tool helping the physician in the management of the disease. This review will focus on the value and applications of ultrasonography in the 2 most frequent rheumatic diseases: rheumatoid arthritis and spondyloarthritis. We will also give some recent data on the usefulness of this imaging technique in the study of musculoskeletal manifestations associated with connective tissue disease.

A comparison between bisphosphonates and other treatments for osteoporosis.

Since their development 30 years ago, bisphosphonates are now one of the standard therapy in the management of osteoporosis. Improvements in terms of anti-resorptive potency have leaded to new molecules available either orally or intravenously, from weekly to yearly administration. Overall tolerance of bisphosphonates is good with regards to the risk of mandibular necrosis, not comparable with those observed in cancer treatment, and with no causal link yet established in osteoporotic patients. Compliance remains poor and should be improved by a better education of the patients about their treatment. Other treatments like teriparatide, raloxifene or strontium ranelate are now also available and give more therapeutic options but also more questions on the best molecule to choose for each patient. There is currently no valid basis for distinguishing in a formal and objective manner the different new-generation bisphosphonates, in terms of efficacy against either vertebral, peripheral or hip fractures. In a same way, comparison between bisphosphonates and the other treatments available for osteoporosis is hard in absence of proper randomised controlled study. This review gives an overview of the recent data on the efficacity and tolerance of bisphosphonates in the different forms of osteoporosis and compares them to the other treatments currently available.

Alternative use of bisphosphonate therapy for rheumatic disease.

Bisphosphonates are widely use for pathologies such as osteoporosis, Paget's disease or bone metastasis. However, their potent antiresorptive properties open new therapeutic opportunities for other conditions associated with an increased focal or systemic bone remodelling. Moreover, apart from their antiresorptive activity, bisphosphonates could also have others properties through a specific analgesic or anti-inflammatory effect. Thus, rheumatic diseases like rheumatoid arthritis, spondylarthritis or SAPHO syndrome (acronym for synovitis, acne, pustulosis, hyperostosis and osteitis) that are associated with systemic and sometimes focal bone loss could be good candidates for bisphosphonate therapy. Other non-inflammatory rheumatic diseases like bone osteonecrosis, algodystrophy, fibrous dysplasia or neuropathic osteoarthropathy are also associated with pain and an increase of focal bone remodelling. Several studies have shown that bisphosphonate could have promising therapeutic potential in these inflammatory or non-inflammatory diseases where therapeutic options are usually few. This review will focus on the new potential alternative indications for bisphosphonate in rheumatic diseases.

Human osteosarcoma cells express functional receptor activator of nuclear factor-kappa B.

RANK, RANK ligand (RANKL) and osteoprotegerin (OPG) are the key regulators of bone metabolism, both in normal and pathological conditions. Previous data have demonstrated that human osteosarcoma biopsies express RANKL as well as OPG, and functional RANK is expressed in a murine osteosarcoma cell line. As RANK expression in human osteosarcoma remains controversial, the aim of the present study was to analyse its expression in vitro in human osteosarcoma cell lines, ex vivo using pathological tissues, and then to determine its functionality in terms of signal transduction pathways modulated by RANKL. RT-PCR analysis and immunohistochemistry experiments revealed that RANK is expressed at both transcriptional and protein levels in MNNG/HOS, Saos-2 and MG-63 human osteosarcoma cell lines, in contrast to the U-2 OS osteosarcoma cell line and human osteoblasts, which were negative. RANK was also expressed in 57% of osteosarcoma biopsies. Furthermore, western blot experiments clearly demonstrated the functionality of RANK. Thus, RANKL significantly induced the phosphorylation of ERK1/2, p38 and IkappaB in RANK-positive osteosarcoma cells. This study is the first report of functional RANK expression in human osteosarcoma cells: this strengthens the involvement of the RANK-RANKL-OPG axis in primary bone tumour biology and identifies novel therapeutic approaches targeting RANK-positive osteosarcoma.

Head movement trajectory in three-dimensional space during orienting behavior toward visual targets in rhesus monkeys.

Head movement trajectories in three-dimensional space were studied in two monkeys with their heads free during natural and spontaneous orienting behavior toward objects of interest displayed in a horizontal plane. The main interest of this study lies in understanding the process responsible for behavioral variability during the execution of head movements, with special reference to "units of movement." The head movements were recorded by an optoelectronic movement analyzer working with passive markers. Algorithms have been designed to reconstruct the three-dimensional trajectories of the center of gravity of the head. Simultaneously, electromyographic activity in the four pairs of suboccipital muscles was studied. A quantitative evaluation of the involvement of the head in orienting behavior toward visual targets shows that the gaze shift is always produced by eye movements in combination with head movements, even with target eccentricities of less than 10 degrees. On the basis of 80 trials performed by the two monkeys, head trajectories and recruitment patterns of the four pairs of suboccipital muscles have been analyzed. We have been able to identify four elementary kinematic units which can be described as a rightward or leftward turning associated with a contralateral or ipsilateral bending. Each of these four elementary units are underlain by a precise fixed recruitment pattern in the four pairs of suboccipital muscles. These four sets of motor strategies can be combined in order to offer a certain amount of plasticity from which the animal builds its own head trajectory.

Gaze strategies during linear motion in head-free humans.

1. Eye-head coordination strategies during horizontal displacements along the y (interaural) axis were investigated in human subjects seated on a sled (linear accelerator device) and tested in head-free conditions. They were instructed to stabilize their gaze, while in motion, on an earth-fixed memorized target and then, after cart immobilization, to look again at the real target. The last part of the test required a corrective saccade, which enabled us to evaluate the error of the subject's displacement estimation. Eye and head compensatory reflexes were tested within the 0.001-0.2 g acceleration range with a sinusoidal motion amplitude of 0.8 m peak to peak. 2. Fixation stabilization on a memorized target was achieved by different eye-head coordination strategies. According to the relative contribution of eye and head motion, a continuum among individual strategies was observed, covering a range of head contributions varying from 0 to almost 100%. All these strategies were well adapted because they contributed to the counteraction of the displacement and led to an optimal gaze accuracy. 3. The use of various gaze strategies during linear motion to achieve the same movement differed according to the subject, but also depended upon motion kinematics. As a rule, head contribution increased as the magnitude of linear acceleration was enhanced. 4. Different eye-head coordination strategies implicated either a linear vestibulo-ocular reflex (LVOR) or ocular responses composed of a combination of antagonistic angular and linear vestibulo-ocular reflexes (AVOR-LVOR). The slow phase direction of these two oculomotor responses for fixation stabilization on the target were compensatory and anticompensatory, respectively. 5. One of the major points of this study was the contribution of the saccadic system to gaze strategies, even in our experimental conditions where the head was free to move. We concluded that vestibular-saccadic cooperation appears to be a common feature in the elaboration of adequate fixation stabilization in daily life situations. 6. The functional coupling of these various subsystems involved in fixation stabilization depended on the range of motion: while the acceleration increased, the saccadic eye movements were replaced by vestibulo-ocular responses whose slow phase direction was opposite that of head motion and, therefore, directed away from the target. 7. Fast components of the nystagmic pattern of eye movements were able to improve gaze position accuracy, bringing the eyes toward the memorized target.(ABSTRACT TRUNCATED AT 400 WORDS)