Adipose-derived mesenchymal stromal cells modulate tendon fibroblast responses to macrophage-induced inflammation in vitro

INTRODUCTION: Macrophage-driven inflammation is a key feature of the early period following tendon repair, but excessive inflammation has been associated with poor clinical outcomes. Modulation of the inflammatory environment using molecular or cellular treatments may provide a means to enhance tendon healing. METHODS: To examine the effect of pro-inflammatory cytokines secreted by macrophages on tendon fibroblasts (TF), we established in vitro models of cytokine and macrophage-induced inflammation. Gene expression, protein expression, and cell viability assays were used to examine TF responses. In an effort to reduce the negative effects of inflammatory cytokines on TFs, adipose-derived mesenchymal stromal cells (ASCs) were incorporated into the model and their ability to modulate inflammation was investigated. RESULTS: The inflammatory cytokine interleukin 1 beta (IL-1β) and macrophages of varying phenotypes induced up-regulation of pro-inflammatory factors and matrix degradation factors and down-regulation of factors related to extracellular matrix formation by TFs in culture. ASCs did not suppress these presumably negative effects induced by IL-1β. However, ASC co-culture with M1 (pro-inflammatory) macrophages successfully suppressed the effects of M1 macrophages on TFs by inducing a phenotypic switch from a pro-inflammatory macrophage phenotype to an anti-inflammatory macrophage phenotype, thus resulting in exposure of TFs to lower levels of pro-inflammatory cytokines (e.g., IL-1β, tumor necrosis factor alpha (TNFα)). CONCLUSIONS: These findings suggest that IL-1β and M1 macrophages are detrimental to tendon healing and that ASC-mediated modulation of the post-operative inflammatory response may be beneficial for tendon healing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-015-0059-4) contains supplementary material, which is available to authorized users

A prospective multi-center cohort study of acute non-displaced fractures of the scaphoid: operative versus non-operative treatment [NCT00205985]

BACKGROUND: Acute scaphoid fractures are common in active adults and do lead to reasonable time lost to work. One important goal of treatment is early return to work or sport. On this background, the adequate treatment of non-displaced acute scaphoid fractures is still under discussion. The aim of this study is to compare time to return to previous activity level comparing surgical versus non-surgical treatment of non-displaced acute scaphoid fractures. METHODS/DESIGN: The study is designed as a non-randomized multiple center cohort study including 12 sites in Germany and Austria. The inclusion period is planned to be 12 months with a follow up of 6 months. Allocation to operative or non-operative treatment is choosen by the patient together with his treating surgeon. The primary outcome is time to return to previous activity level adapted for loading of the wrist in daily life as measured by a newly developed questionnaire (PLDL-wrist). Factors identified a priori to be associated with the outcome, e.g., poverty status, age, education, smoking status, gender, and occupation, are measured to ensure adequate control for their potential confounding effects. DISCUSSION: The rationale and the design of a multiple center cohort study are presented. As it is not considered feasible to randomize patients in this study, potential confounding effects need to be controlled adequately

The influence of foot geometry on the calcaneal osteotomy angle based on two-dimensional static force analyses

Background: Malalignment of the hindfoot can be corrected with a calcaneal osteotomy (CO). A well-selected osteotomy angle in the sagittal plane will reduce the shear force in the osteotomy plane while walking. The purpose was to determine the presence of a relationship between the foot geometry and loading of the calcaneus, which influences the choice of the preferred CO angle. Methods A static free body force analysis was made of the posterior calcaneal fragment in the second half of the stance phase to determine the main loads: the plantar apeunorosis (PA) and Achilles tendon (AT). The third load is on the osteotomy surface which should be oriented such that the shear component of the force is zero. The force direction of the PA and AT was measured on 58 MRIs of the foot, and the force ratio between both structures was taken from the literature. In addition the PA-to-AT force ratio was estimated for different foot geometries to identify the relationship. Results: Based on the wish to minimize the shear force during walking, a mean CO angle was determined to be 33º (SD8) relative to the foot sole. In pes planus foot geometry, the angle should be higher than the mean. In pes cavus foot geometry, the angle should be smaller. Conclusion: Foot geometry, in particular the relative foot heights is a determinant for the individual angle in performing the sliding calcaneal osteotomy. It is recommended to take into account the foot geometry (arch) when deciding on the CO angle for hindfoot correction.Biomechanical EngineeringMechanical, Maritime and Materials Engineerin

Carpal tunnel syndrome and the use of computer mouse and keyboard: A systematic review

<p>Abstract</p> <p>Background</p> <p>This review examines evidence for an association between computer work and carpal tunnel syndrome (CTS).</p> <p>Methods</p> <p>A systematic review of studies of computer work and CTS was performed. Supplementary, longitudinal studies of low force, repetitive work and CTS, and studies of possible pathophysiological mechanisms were evaluated.</p> <p>Results</p> <p>Eight epidemiological studies of the association between computer work and CTS were identified. All eight studies had one or more limitation including imprecise exposure and outcome assessment, low statistical power or potentially serious biases. In three of the studies an exposure-response association was observed but because of possible misclassification no firm conclusions could be drawn. Three of the studies found risks below 1. Also longitudinal studies of repetitive low-force non-computer work (n = 3) were reviewed but these studies did not add evidence to an association. Measurements of carpal tunnel pressure (CTP) under conditions typically observed among computer users showed pressure values below levels considered harmful. However, during actual mouse use one study showed an increase of CTP to potentially harmful levels. The long term effects of prolonged or repeatedly increased pressures at these levels are not known, however.</p> <p>Conclusion</p> <p>There is insufficient epidemiological evidence that computer work causes CTS.</p

Healing of the aponeurosis during recovery from aponeurotomy: morphological and histological adaptation and related changes in mechanical properties

Aponeurotomy, which is the transection of an aponeurosis perpendicular to its length, is performed to lengthen spastic and/or short muscles. During recovery, the cut ends of the aponeurosis are reconnected by new connective tissue bridging both ends. The aim of this study is to investigate the histological features of this new connective tissue as well as its mechanical properties after recovery from aponeurotomy. For this purpose, aponeurotomy was performed on the proximal aponeurosis of rat m. gastrocnemius medialis (GM), which was followed by six weeks of recovery. The lengths of aponeurotic tissues were measured as a function of active muscle length. The results are compared to a control group as well as to the acute effects and a sham operated group. Activation of the muscle at increasing lengths after aponeurotomy caused a gap between the cut ends of the aponeurosis. However, after recovery, new connective tissue is formed bridging the aponeurotic ends, consisting of thin collagen fibres, which are densely packed and generally arranged in the direction of the aponeurosis. The number of fibroblasts was three to five times higher than that of aponeurotic tissue of the intact parts as well as that of the acute and sham operated muscles. The strain of the new connective tissue as a function of active muscle length was shown to be about three times higher than that of the aponeurosis. It is concluded that the inserted new aponeurotic tissue is more compliant and that the aponeurosis becomes 10-15% longer than in untreated muscle. As a consequence, the muscle fibres located distally to the new aponeurotic tissue will become shorter than prior to aponeurotomy. This explains a shift of the length-force curve, which favours the restoration of the range of joint motion. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved

Splinting or surgery for carpal tunnel syndrome? Design of a randomized controlled trial [ISRCTN18853827]

BACKGROUND: Carpal tunnel syndrome is a common disorder, which can be treated with surgery or conservative options. However, there is insufficient evidence and no consensus among physicians with regard to the preferred treatment for carpal tunnel syndrome. Therefore, a randomized controlled trial is conducted to compare the short- and long-term efficacy of surgery and splinting in patients with carpal tunnel syndrome. An attempt is also made to avoid the (methodological) limitations encountered in earlier trials on the efficacy of various treatment options for carpal tunnel syndrome. METHODS: Patients of 18 years and older, with clinically and electrophysiologically confirmed idiopathic carpal tunnel syndrome, are recruited by neurologists in 13 hospitals. Patients included in the study are randomly allocated to either open carpal tunnel release or wrist splinting during the night for at least 6 weeks. The primary outcomes are general improvement, waking up at night and severity of symptoms (main complaint, night and daytime pain, paraesthesia and hypoesthesia). Outcomes are assessed up to 18 months after randomization

Ulnar-sided wrist pain. Part I: anatomy and physical examination

Ulnar-sided wrist pain is a common complaint, and it presents a diagnostic challenge for hand surgeons and radiologists. The complex anatomy of this region, combined with the small size of structures and subtle imaging findings, compound this problem. A thorough understanding of ulnar-sided wrist anatomy and a systematic clinical examination of this region are essential in arriving at an accurate diagnosis. In part I of this review, ulnar-sided wrist anatomy and clinical examination are discussed for a more comprehensive understanding of ulnar-sided wrist pain

Carpal Tunnel Syndrome: A Review of the Recent Literature

Carpal Tunnel Syndrome (CTS) remains a puzzling and disabling condition present in 3.8% of the general population. CTS is the most well-known and frequent form of median nerve entrapment, and accounts for 90% of all entrapment neuropathies. This review aims to provide an overview of this common condition, with an emphasis on the pathophysiology involved in CTS. The clinical presentation and risk factors associated with CTS are discussed in this paper. Also, the various methods of diagnosis are explored; including nerve conduction studies, ultrasound, and magnetic resonance imaging

Ulnar-sided wrist pain. II. Clinical imaging and treatment

Pain at the ulnar aspect of the wrist is a diagnostic challenge for hand surgeons and radiologists due to the small and complex anatomical structures involved. In this article, imaging modalities including radiography, arthrography, ultrasound (US), computed tomography (CT), CT arthrography, magnetic resonance (MR) imaging, and MR arthrography are compared with regard to differential diagnosis. Clinical imaging findings are reviewed for a more comprehensive understanding of this disorder. Treatments for the common diseases that cause the ulnar-sided wrist pain including extensor carpi ulnaris (ECU) tendonitis, flexor carpi ulnaris (FCU) tendonitis, pisotriquetral arthritis, triangular fibrocartilage complex (TFCC) lesions, ulnar impaction, lunotriquetral (LT) instability, and distal radioulnar joint (DRUJ) instability are reviewed