Objectives. The goal of this study was to determine whether intra-articular administration of the potentially anti-fibrotic agent decorin influences the expression of genes involved in the fibrotic cascade, and ultimately leads to less contracture, in an animal model. Methods. A total of 18 rabbits underwent an operation on their right knees to form contractures. Six limbs in group 1 received four intra-articular injections of decorin; six limbs in group 2 received four intra-articular injections of bovine serum albumin (BSA) over eight days; six limbs in group 3 received no injections. The contracted limbs of rabbits in group 1 were biomechanically and genetically compared with the contracted limbs of rabbits in groups 2 and 3, with the use of a calibrated joint measuring device and custom microarray, respectively. Results. There was no statistical difference in the flexion contracture angles between those limbs that received intra-articular decorin versus those that received intra-articular BSA (66° vs 69°; p = 0.41). Likewise, there was no statistical difference between those limbs that received intra-articular decorin versus those who had no injection (66° vs 72°; p = 0.27). When compared with BSA, decorin led to a statistically significant increase in the mRNA expression of 12 genes (p < 0.01). In addition, there was a statistical change in the mRNA expression of three genes, when compared with those without injection. . Conclusions. In this model, when administered intra-articularly at eight weeks, 2 mg of decorin had no significant effect on joint contractures. However, our genetic analysis revealed a significant alteration in several fibrotic genes. Cite this article: Bone Joint Res 2014;3:82–8

Summary. Based upon genetic analysis, decorin is an exciting pharmacologic agent of potential anti-fibrogenic effect on arthrofibrosis in our animal model. Introduction. While the pathophysiology of arthrofibrosis is not fully understood, some anti-fibrotic molecules such as decorin could potentially be used for the prevention or treatment of joint stiffness. The goal of this study was to determine whether intra-articular administration of decorin influences the expression of genes involved in the fibrotic cascade ultimately leading to less contracture in an animal model. Material and Methods. Eighteen rabbits had their right knees operated on to form contractures. The left knees served as controls. The 6 right limbs in the experimental group (Group 1) received four 500 ug/ml intra-articular injections of decorin over 8 days starting at 8 week, for a total of 2 mg. The 6 right limbs in the first control group (Group 2) received four intra-articular injections of bovine serum albumin (BSA) over 8 days starting at 8 weeks as well. The 6 six right limbs in the second control group (Group 3) received no injections. The contracted limbs of rabbits in Group 1 were biomechanically and genetically compared to the contracted limbs of rabbits in Groups 2 and 3 with the use of a calibrated joint measuring device and custom microarray, respectively. Results. There was no statistical difference in the flexion contracture angles between those right limbs that received intra-articular decorin versus those that received intra-articular BSA (66° vs. 69°; p = 0.41). Likewise, there was no statistical difference between those right limbs that received intra-articular decorin as opposed to those who had no injection (66° vs. 72°; p = 0.27). The lack of significance remained when the control left limbs were taken into account (p > 0.40). When compared to bovine serum albumin (BSA), decorin led to a statistically significant increase in the mRNA expression of 5 genes: substance P, neuropeptide γ, and neurokinin A, cyclin E2, and MMP-9 (p < 0.001). In addition, there was a statistically significant decrease in fibroblast growth factor receptor-2 (FGFR-2), rho-associated coiled-coil containing protein kinase-1 (ROCK-1), and vascular cell adhesion molecule-1 (VCAM-1) genes when intra-articular decorin was compared to no injection (p < 0.001). Conclusions. In this model, when administered intra-articularly at 8 weeks, 2 mg of decorin had no significant effect on joint contractures. However, our genetic analysis revealed a significant alteration in the expression of several fibrotic genes. Further studies investigating the route of administration, dosing, frequency, and timing are required before definitive conclusions may be drawn on the effects of decorin on joint contractures

Our objective was to determine the plasma levels of substance P (SP) in patients with postoperative stiffness after arthroscopic rotator cuff repair.

Plasma samples were obtained at 15 months from surgery from 2 groups of patients who underwent arthroscopic repair of a rotator cuff tear. In Group 1, 30 subjects (14 men and 16 women, mean age: 64.6 years, range 47 to 78) with shoulder stiffness 15 months after arthroscopic rotator cuff repair were recruited. In Group 2, 30 patients (11 men and 19 women, mean age: 57.8 years, range 45 to 77) were evaluated 15 months after successful arthroscopic rotator cuff repair. Immunoassays were performed with commercially available assay kits to detect the plasma levels of SP.

The mean plasma levels of SP in patients with postoperative stiffness were significantly greater than those in the control group (81.06 ± 27.76 versus 23.49 ± 5.64, P < 0.05).

The plasma concentrations of substance P in patients with shoulder stiffness after arthroscopic rotator cuff repair are higher compared to plasma levels of SP in patients with a good postoperative outcome. The neuronal upregulation of SP shown in the plasma of patients with post operative shoulder stiffness may underlay not only the symptoms of adhesive capsulitis, but also its development.

Postoperative stiffness (POS) of the shoulder may occur after an apparently successful reconstruction of a rotator cuff tear.

The role of the peripheral nervous system in tissue healing has only recently been recognized.

We determined the plasma levels of SP in patients with postoperative stiffness after arthroscopic repair of a rotator cuff tear, and compared them with those in patients with a good outcome after arthroscopic rotator cuff repair.

Plasma samples were obtained at 15 months from surgery from 2 groups of patients who underwent arthroscopic repair of a rotator cuff tear. In Group 1, 30 subjects (14 men and 16 women, mean age: 64.6 years, range 47 to 78) with shoulder stiffness 15 months after arthroscopic rotator cuff repair were recruited. In Group 2, 30 patients (11 men and 19 women, mean age: 57.8 years, range 45 to 77) were evaluated 15 months after successful arthroscopic rotator cuff repair. Immunoassays were performed with commercially available assay kits to detect the plasma levels of SP.

Statistical analysis were performed with Wilcoxon Sign Rank test. Significance was set at P< 0.05

The concentrations of the neuropeptide SP in sera were measurable in all patients. Patients with postoperative stiffness had statistically significant greater plasma levels of SP than patients in whom arthroscopic repair of rotator cuff tears had resulted in a good outcome (P < 0.05)

Postoperative stiffness (POS) of the shoulder may occur after an apparently successful reconstruction of a rotator cuff tear.

An increased amount of SP in the subacromial bursa has been correlated with the pain caused by rotator cuff disease.

SP stimulates DNA synthesis in fibroblasts, which are the cellular components of the adhesive capsulitis of the shoulder. Also, SP is a pain transmitter peptide, and pain may cause a secondary muscular and/or capsular contracture.

Our results show that the plasma concentrations of substance P in patients with shoulder stiffness after arthroscopic rotator cuff repair are higher compared to plasma levels of SP in patients with a good postoperative outcome.

We cannot determine the cause of POS in our patients, but the findings of this study suggest a possible neuronal role in the pathophysiology of POS after arthroscopic repair of rotator cuff tears. The knowledge of the pathophysiological role of sensory nerve peptides in tissue repair in these patients could open new therapeutic options to manage conditions of the musculo-skeletal system with impaired tissue-nervous system interaction.

Objectives. Sustained intra-articular delivery of pharmacological agents is an attractive modality but requires use of a safe carrier that would not induce cartilage damage or fibrosis. Collagen scaffolds are widely available and could be used intra-articularly, but no investigation has looked at the safety of collagen scaffolds within synovial joints. The aim of this study was to determine the safety of collagen scaffold implantation in a validated in vivo animal model of knee arthrofibrosis. Materials and Methods. A total of 96 rabbits were randomly and equally assigned to four different groups: arthrotomy alone; arthrotomy and collagen scaffold placement; contracture surgery; and contracture surgery and collagen scaffold placement. Animals were killed in equal numbers at 72 hours, two weeks, eight weeks, and 24 weeks. Joint contracture was measured, and cartilage and synovial samples underwent histological analysis. Results. Animals that underwent arthrotomy had equivalent joint contractures regardless of scaffold implantation (-13.9° versus -10.9°, equivalence limit 15°). Animals that underwent surgery to induce contracture did not demonstrate equivalent joint contractures with (41.8°) or without (53.9°) collagen scaffold implantation. Chondral damage occurred in similar rates with (11 of 48) and without (nine of 48) scaffold implantation. No significant difference in synovitis was noted between groups. Absorption of the collagen scaffold occurred within eight weeks in all animals. Conclusion. Our data suggest that intra-articular implantation of a collagen sponge does not induce synovitis or cartilage damage. Implantation in a native joint does not seem to induce contracture. Implantation of the collagen sponge in a rabbit knee model of contracture may decrease the severity of the contracture. Cite this article: J. A. Walker, T. J. Ewald, E. Lewallen, A. Van Wijnen, A. D. Hanssen, B. F. Morrey, M. E. Morrey, M. P. Abdel, J. Sanchez-Sotelo. Intra-articular implantation of collagen scaffold carriers is safe in both native and arthrofibrotic rabbit knee joints. Bone Joint Res 2016;6:162–171. DOI: 10.1302/2046-3758.63.BJR-2016-0193

Distal arthrogryposis (DA) is a collection of rare developmental disorders characterized by congenital joint contractures. Most arthrogryposis mutations are in muscle- and joint-related genes, and the anatomical defects originate cell-autonomously within the musculoskeletal tissues. However, gain-of-function (GOF) mutations in PIEZO2, a principal mechanosensor in somatosensation, cause DA subtype 5 via unknown mechanisms. We show that expression of a GOF PIEZO2 mutation in proprioceptive sensory neurons mainly innervating muscle spindles and tendons is sufficient to induce DA5-like phenotypes in mice. Overactive PIEZO2 causes anatomical defects via increased activity within the peripheral nervous system during postnatal development. Surprisingly, overactive PIEZO2 is likely to cause joint abnormalities via increased exocytosis from sensory neuron endings without involving motor circuitry. This reveals a role for somatosensory neurons: excessive mechanosensation within these neurons disrupts musculoskeletal development. We also present proof-of-concept that Botox injection or dietary treatment can counteract the effect of overactive PIEZO2 function to evade DA-like phenotypes in mice when applied during a developmental critical period. These approaches might have clinical applications. Beyond this, our findings call attention to the importance of considering sensory mechanotransduction when diagnosing and treating other musculoskeletal disorders. Acknowledgements: Our work is supported by National Institutes of Health grant (R35 NS105067, R01 DE022358, R25 SC3GM127195, R25 GM07138, R01GM133845, intramural) and Howard Hughes Medical Institute

Abstract. Introduction. Total knee replacement (TKR) in patients with skeletal dysplasia is technically challenging surgery due to deformity, joint contracture, and associated co-morbidities. The aim of this study is to follow up patients with skeletal dysplasia following a TKR. Methodology. We retrospectively reviewed 22 patients with skeletal dysplasia who underwent 31 TKRs at our institution between 2006 and 2022. Clinical notes, operative records and radiographic data were reviewed. Results. Achondroplasia was the most common skeletal dysplasia (8), followed by Chondrodysplasia punctata (7) and Spondyloepiphyseal dysplasia (5). There were fourteen men and eight women with mean age of 51 years (28 to 73). The average height of patients was 1.4 metres (1.16–1.75) and the mean weight was 64.8 Kg (34.3–100). The mean follow up duration was 68.32 months (1–161). Three patients died during follow up. Custom implants were required in twelve patients (38.71%). Custom jigs were utilised in six patients and two patients underwent robotic assisted surgery. Hinged TKR was used in seventeen patients (54.84%), posterior stabilised TKR in nine patients (29.03%), and cruciate retaining TKR in five patients (16.13%). One patient underwent a patella resurfacing for persistent anterior knee pain and another had an intra-operative medial tibial plateau fracture which was managed with fixation. No revisions occurred during the follow up period. Conclusion. Despite the technical challenges and complexity of TKR within this unique patient group, we demonstrate good implant survivorship during the study period. Cross sectional imaging is recommended preoperatively for precise planning and templating

Aims. Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits. Methods. A group of 12 skeletally mature rabbits were randomly divided into two groups. One group received subcutaneous (SQ) saline, and a second group received SQ ketotifen injections. Biomechanical data were collected at eight, ten, 16, and 24 weeks. At the time of necropsy, posterior capsule tissue was collected for histopathological and gene expression analyses (messenger RNA (mRNA) and protein). Results. At the 24-week timepoint, there was a statistically significant increase in passive extension among rabbits treated with ketotifen compared to those treated with saline (p = 0.03). However, no difference in capsular stiffness was detected. Histopathological data failed to demonstrate a decrease in the density of fibrous tissue or a decrease in α-smooth muscle actin (α-SMA) staining with ketotifen treatment. In contrast, tryptase and α-SMA protein expression in the ketotifen group were decreased when compared to saline controls (p = 0.007 and p = 0.01, respectively). Furthermore, there was a significant decrease in α-SMA (ACTA2) gene expression in the ketotifen group compared to the control group (p < 0.001). Conclusion. Collectively, these data suggest that ketotifen mitigates the severity of contracture formation in a rabbit model of arthrofibrosis. Cite this article: Bone Joint Res 2020;9(6):302–310

Aims. The Precice intramedullary limb-lengthening system has demonstrated significant benefits over external fixation lengthening methods, leading to a paradigm shift in limb lengthening. This study compares outcomes following antegrade and retrograde femoral lengthening in both adolescent and adult patients. Patients and Methods. A retrospective review of prospectively collected data was undertaken of a consecutive series of 107 femoral lengthening operations in 92 patients. In total, 73 antegrade nails and 34 retrograde nails were inserted. Outcome was assessed by the regenerate healing index (HI), hip and knee range of movement (ROM), and the presence of any complications. Results. The mean lengthening was 4.65 cm (1.5 to 8) in the antegrade group and 4.64 cm (1.6 to 8) in the retrograde group. Of the 107 lengthenings, 100 had sufficient datapoints to calculate the mean HI. This was 31.6 days/cm (15 to 108). There was a trend toward a lower (better) HI with an antegrade nail and better outcomes in adolescent patients, but these were not statistically significant. Hip and knee ROM was maintained and/or improved following commencement of femoral lengthening in 44 patients (60%) of antegrade nails and 13 patients (38%) of retrograde nails. In female patients, loss of movement occurred both earlier and following less total length achieved. Minor implant complications included locking bolt migration and in one patient deformity of the nail, but no implant failed to lengthen and there were no deep infections. Three patients had delayed union, five patients required surgical intervention for joint contracture. Conclusion. This study confirms excellent results in femoral lengthening with antegrade and retrograde Precice nails. There is a trend for better healing and less restriction in hip and knee movement following antegrade nails. There are clinical scenarios, that mandate the use of a retrograde nail. However, when these are not present, we recommend the use of antegrade nailing. Cite this article: Bone Joint J 2019;101-B:1168–1176

Objectives. The aims of this study were to determine whether the administration of anti-inflammatory and antifibrotic agents affect the proliferation, viability, and expression of markers involved in the fibrotic development of the fibroblasts obtained from arthrofibrotic tissue in vitro, and to evaluate the effect of the agents on arthrofibrosis prevention in vivo. Methods. Dexamethasone, diclofenac, and decorin, in different concentrations, were employed to treat fibroblasts from arthrofibrotic tissue (AFib). Cell proliferation was measured by DNA quantitation, and viability was analyzed by Live/Dead staining. The levels of procollagen type I N-terminal propeptide (PINP) and procollagen type III N-terminal propeptide (PIIINP) were evaluated with enzyme-linked immunosorbent assay (ELISA) kits. In addition, the expressions of fibrotic markers were detected by real-time polymerase chain reaction (PCR). Fibroblasts isolated from healthy tissue (Fib) served as control. Further, a rabbit model of joint contracture was used to evaluate the antifibrotic effect of the three different agents. Results. Dexamethasone maintained the viability and promoted the proliferation of AFib. Diclofenac decreased the viability and inhibited the cell proliferation during the first week of cultivation. However, decorin inhibited AFib proliferation and downregulated the expressions of fibrotic markers. Additionally, decorin could improve the flexion contracture angle and inhibit the deposition of interstitial matrix components in the rabbit joint model. Conclusion. Decorin decreased the expression of myofibroblast markers in AFib, inhibited the proliferation of AFib, and prevented the initial procedure of arthrofibrosis in vivo, suggesting that decorin could be a promising treatment to inhibit the development of arthrofibrosis. Cite this article: X. Tang, S. Teng, M. Petri, C. Krettek, C. Liu, M. Jagodzinski. The effect of anti-inflammatory and antifibrotic agents on fibroblasts obtained from arthrofibrotic tissue: An in vitro and in vivo study. Bone Joint Res 2018;7:213–222. DOI: 10.1302/2046-3758.73.BJR-2017-0219.R2

We describe the natural history of a rabbit knee model of permanent post-traumatic joint contractures. Twenty-four skeletally mature female NZW rabbits had five-mm-squares of cortical bone removed from both femoral condyles. An extra-articular K-wire immobilized the knee joint in flexion. The K-wire was removed eight weeks later and the rabbits were divided into four groups depending on the remobilization time. The average extension loss for the experimental knees in the zero, eight, sixteen and thirty-two weeks remobilization groups was thirty-eight, thirty-two, twenty-one and twenty degrees, respectively. The motion loss stabilized in the later time intervals suggesting permanent contractures had developed. The contralateral unoperated knees average extension loss was nine degrees. The purpose of this study was to develop a rabbit knee model of post-traumatic contractures. A simulated intra-articular fracture plus eight weeks of immobilization leads to a permanent joint contracture even after thirty-two weeks of remobilization. This animal model of human post-traumatic joint contractures will allow further studies investigating mechanisms underlying the process. Twenty-four skeletally mature female NZW rabbits had 5 mm squares of cortical bone removed from both femoral condyles. An extra-articular Kirschner wire (K-wire) immobilized the knee in flexion. A second operation was performed eight weeks later to remove the K-wire. The rabbits were divided into four groups. Hind limbs were dissected, preserving the joint capsule. A device allowing six degrees-of-freedom coupled to a material testing system which applied a 0.2 Nm torque measured joint angles. Statistical analysis was performed using ANOVA with a posthoc Student-Newman-Keuls test. Data are presented as mean ± SD. The loss of extension for the experimental knees in the zero and eight weeks remobilization groups was significantly greater than the values of all contralateral unoperated knees. The loss of extension for the experimental knees in the sixteen and thirty-two weeks remobilization groups was also greater than the contralateral knees, although it was not statistically significant (p = 0.07). With this model, the severity of the contracture decreased with time of remobilization. However, the degree of contracture stabilized between sixteen and thirty-two weeks of remobilization, suggesting that the joints had developed a permanent contracture. This mimics the human scenario of permanent post-traumatic joint contractures. Funding: has not been received from a commercial party. This work was supported by The Alberta Heritage Foundation for Medical Research. Please contact author for tables and/or graphs

The objective of this report was to evaluate myofibroblast numbers in human elbow anterior joint capsules. Joint capsules were obtained from six patients with post-traumatic contractures and from six elbow joints of age-matched organ donors. Frozen sections were labeled with α-smooth muscle actin (α-SMA), a marker of myofibroblasts. Myofibroblasts were identified in both experimental and control tissues. Myofibroblast numbers and percentage of total cells were significantly elevated in the capsules of patients (919 ± 187; 36 ± 0.04%) when compared to organ donor control tissue (485 ± 335; 9 ± 0.04%). Future work will look at the expression of myofibroblast modulators in human elbow joint contractures. The purpose of this study was to determine whether myofibroblasts are associated with human elbow joint contractures. Myofibroblast numbers and percentage of myofibroblasts to total cells were significantly increased in anterior elbow joint capsules of patients with post-traumatic contractures. Methods to alter myofibroblast expression may be strategies to prevent or treat post-traumatic elbow joint contractures. Joint capsules were obtained from six patients (age 33±13 yrs, preoperative flexion-extension arc range of motion 58°±15°) and from six elbow joints of organ donors free of contractures (age 26±15 yrs). Frozen sections were double labeled using monoclonal antibodies to α-smooth muscle actin (α-SMA) with peroxidase conjugated secondary antibodies, and affinity purified antibodies to laminin with Elexa Fluor 488 conjugated secondary antibodies. The laminin antibodies label components of blood vessels, to differentiate between α-SMA expression associated with blood vessels or myofibroblasts. Endogenous peroxidases were quenched and 10% normal goat serum was used as a blocking agent. DAB/peroxide substrate was added for thirteen minutes. DAPI was applied to label nuclei. Cell nuclei associated with α-SMA and not with laminin were counted as myofibroblasts. Myofibroblast numbers and percentage of total cells were significantly increased (t-test, p < 0.05) in the joint capsules of the patients when compared to organ donor control tissue. Total cell numbers were not significantly different in the patient and control tissue. Modulators of α-SMA expression and myofibroblast formation include growth factors and matrix molecule components. Future work will look at the expression of these modulators in human elbow joint contractures. Funding: Funding has not been received from a commercial party. This work was supported by The Alberta Heritage Foundation for Medical Research. Please contact author for tables and/or diagrams

Aims. Animal models have been developed that allow simulation of post-traumatic joint contracture. One such model involves contracture-forming surgery followed by surgical capsular release. This model allows testing of antifibrotic agents, such as rosiglitazone. Methods. A total of 20 rabbits underwent contracture-forming surgery. Eight weeks later, the animals underwent a surgical capsular release. Ten animals received rosiglitazone (intramuscular initially, then orally). The animals were sacrificed following 16 weeks of free cage mobilisation. The joints were tested biomechanically, and the posterior capsule was assessed histologically and via genetic microarray analysis. Results. There was no significant difference in post-traumatic contracture between the rosiglitazone and control groups (33° (standard deviation (. sd. ) 11) vs 37° (. sd. 14), respectively; p = 0.4). There was no difference in number or percentage of myofibroblasts. Importantly, there were ten genes and 17 pathways that were significantly modulated by rosiglitazone in the posterior capsule. Discussion. Rosiglitazone significantly altered the genetic expression of the posterior capsular tissue in a rabbit model, with ten genes and 17 pathways demonstrating significant modulation. However, there was no significant effect on biomechanical or histological properties. Cite this article: M. P. Abdel. Effectiveness of rosiglitazone in reducing flexion contracture in a rabbit model of arthrofibrosis with surgical capsular release: A biomechanical, histological, and genetic analysis. Bone Joint Res 2016;5:11–17. doi: 10.1302/2046-3758.51.2000593

Summary. Previous work in a rabbit model of post-traumatic joint contractures shows that the mast cell stabilizer ketotifen decreases contracture severity. We show here that ketotifen decreases collagen gel contraction mediated by rabbit joint capsule fibroblasts when mast cells are present. Introduction. Ketotifen was shown to decrease contracture severity and associated joint capsule fibrosis in an animal model of post-traumatic joint contractures. Ketotifen prevents the release of profibrotic growth factors from mast cells (MC). An in vitro collagen gel contraction assay is used to examine the effect of ketotifen on joint capsule fibroblasts obtained from this animal model. Methods. Six New Zealand White rabbits had a standardised procedure to induce post-traumatic joint contractures and the joint capsule was harvested 4 weeks later. The capsules were minced, placed into T75 culture flasks and incubated at 37. 0. C in a humidified atmosphere containing 5% CO. 2. The Joint Capsule fibroblasts (JC, 2.5 × 10. 5. cells/mL) were mixed with neutralised collagen solution composed of 59% neutralised PureCol collagen I, serum free DMEM/F12 with 1x serum replacement and 1x antibiotic-antimycotic. Aliquots of solution were then cast into wells of a tissue culture plate. Gelation occurred over 3h at 37°C in a humidified incubator. The collagen gel/cells were maintained with DMEM/F-12 plus 1% serum replacement and 1% antibiotic-antimycotic and incubated at 37°C for 12 h. The gels were released and gel area was calculated up to 72h post-release. Different experiments were conducted with various combinations of a human mast cell line (HMC-1, 7.5 × 10. 5. cells/mL), the neuropeptide Substance P (SP, 10. −6. M) and Ketotifen fumurate at 10. −4. , 10. −6. , 10. −8. and 10. −10. M. The various interventions were combined with the JC and collagen gel during the gelation step. Statistical comparisons used a two way ANOVA with a Posthoc Tukey test. Significance was set at p < 0.05. Results. The JC contracted the collagen gels in all conditions, with statistically significant differences between time intervals from 6 h to 72 h. When ketotifen alone was added to JC, there was no effect on collagen gel contraction in the range of doses tested. Adding MC to JC led to a significantly increased rate of gel contraction that was inhibited by ketotifen in a dose-dependent manner. The effect was maximal with a concentration of 10. −4. M while the effect was absent by the dose of 10. −10. M. There were statistically significant differences amongst different doses except for comparisons between doses closest to each other (10. −4. vs 10. −6. , 10. −6. vs 10. −8. , 10. −8. vs 10. −10. M). Including SP with MC and JC further increased the rate of gel contraction, which was also significantly inhibited by ketotifen in a similar dose-dependent fashion. Discussion/Conclusion. Fibroblasts from rabbit joint capsules contract collagen gels with the effect enhanced by the addition of mast cells. Ketotifen prevents the release of mediators by mast cells, and ketotifen modified the collagen gel assay. It appears that the inhibition of the gel contraction by the fibroblasts is via mast cell stabilization since ketotifen had no direct affect on the fibroblasts in the concentrations evaluated. Ketotifen is a medication used in the chronic treatment of asthma. It has a wide safety profile, it is already approved for human use and it is available in oral preparations

Purpose: To determine if mast cell activity is vital to the induction of joint capsule fibrosis and contracture formation in a rabbit model of posttraumatic joint contracture. Method: To reproducibly induce joint contractures, we used a model of surgical injury and immobilization of the knee in skeletally mature New Zealand white rabbits. Four animals groups were studied: a non-operative control group (CON), an operative contracture group (ORC) and two-operative groups treated with a mast cell stabilizer, Ketotifen fumarate at doses of 0.5mg/kg (KF0.5) and 1.0mg/kg (KF1.0) twice daily subcutaneously, respectively. Animals were sacrificed after 8 weeks of immobilization. Flexion contractures (biomechanics), cellular counts of myofibroblasts and mast cells within the joint capsule (immunohistochemistry) and the joint capsule protein expression of TGF-β1, collagen I and III were quantified (western blots). Biomechanical data was interpreted using a linear regression analysis of repeated measures and an ANOVA analysis of variance was used for molecular data. Significance was defined at p< 0.05 for all statistical tests. Results: Flexion contractures were most severe in the ORC group and treatment with Ketotifen (both KF0.5 and KF1.0) significantly reduced contracture severity by 52% and 42%, respectively (p< 0.03). Joint capsule myofibroblast and mast cell hyperplasia was a prominent feature of the more severely contracted ORC group and myofibroblast and mast cell numbers were dramatically reduced in both Ketotifen groups (p< 0.001). The expression of TGF-β1 and collagen I was also increased in the ORC group and significantly reduced in both Ketotifen groups (p< 0.01). Conclusion: Joint capsule fibrosis, characterized by hyperplasia of myofibroblasts and mast cells and enhanced collagen deposition, is a prominent feature of posttraumatic joint contractures in this animal model. Treatment with a mast cell stabilizer reduced the molecular markers of joint capsule fibrosis and the resultant biomechanical severity of contracture formation. These results suggest mast cell activity may be an important process in the development of posttraumatic contractures and future work is needed to determine if pharmacological inhibition of mast cell activity has a preventative or therapeutic role in humans

Purpose. Recent work has shown that joint contracture severity can be decreased with the mast cell stabilizer ketotifen in association with decreased numbers of myofibroblasts and mast cells in the joint capsule of a rabbit model of post-traumatic contractures. Neuropeptides such as Substance P (SP) can induce mast cells to release growth factors. Using a gel contraction assay, we test the hypothesis that joint capsule cell-mediated contraction of a collagen gel can be enhanced with SP, but the effect is magnified in the presence of mast cells. Method. Anterior elbow joint capsules were obtained at the time of surgical release from 2 men (age 34 and 54) and 1 woman (age 40) with chronic (> 1 year) post-traumatic joint contractures. The human mast cell line HMC-1 (Mayo Clinic, Rochester), SP and the NK1 receptor antagonist RP67580 (Sigma, Oakville, ON) were used. NK1 is the SP receptor. Neutralized Collagen solution composed with 58% Vitrogen 100 purified collagen mixed with HMC-1 cells only (7.5 105), human capsule cells (2.5 105), or human capsule cells (2.5 105) and 7.5 105 mast cells (1:3) were cast into 24- well tissue culture plates. In some experiments, SP (1 × 10. −5. M) +/− RP67580 (0.5 mM) were added. The gels were maintained with 0.5 ml DMEM composed with 2% BSA and incubated at 37C for 12 h for gelation to occur. The gels were then detached from the wall and the bottom of culture plate wells, and photographed at regular intervals up to 72 hours. Gel contraction studies were carried out on passage 4 and done in triplicate for each patient. The average value of each patients triplicate was combined to give a mean contraction at each time point. Statistical analysis involved an ANOVA with posthoc Bonferroni correction. P < 0.001 was significant. Results. Mast cells alone or with SP were unable to contract collagen gels. Joint capsule cells were able to contract the collagen gels and this was enhanced in the presence of SP, although not statistically significant. Joint capsule cells combined with mast cells enhanced the gel contraction more than joint capsule cells alone or with SP (p<0.001). The addition of SP accelerated the joint capsule cell-mediated gel contraction in the presence of mast cells the greatest (p<0.001 over all other conditions). The inhibitor RP67580 completely abolished the collagen gel contraction of the joint capsule cells in all conditions. Conclusion. The in vitro experiment shows that joint capsule cell function, in the form of collagen gel contraction, is modified by the presence of mast cells and neuropeptides. These findings are significant as they strengthen the hypothesis that a myofibroblast mast cell neuropeptide fibrosis axis may be contributing to the joint capsule changes underling the loss of motion in post-traumatic joint contractures. In vivo studies with the rabbit model of post-traumatic contractures will be performed using the compounds examined in the current study

Ligaments, menisci and joint capsules were obtained from experimental knees with post-traumatic joint contractures and their unoperated contralateral controls in 6 rabbits. Relative mRNA expression was altered for six of seven matrix molecules, growth factors and _-SMA (myofibroblast marker) in the joint capsule, four of seven molecules in the ACL, and two of seven molecules in the MCL and medial meniscus. The joint capsule had the most molecules with altered expression corresponding to it’s acknowledged key role in joint contracture development. Changes in molecular expression of several joint structures in post-traumatic contractures is similar to changes seen following ligament injury. To evaluate alteration of mRNA expression in ligaments, meniscus and joint capsules in post-traumatic contractures. mRNA expression was altered most frequently in the joint capsule. The mRNA expression alterations in the joint capsule reflect it’s significant contribution to contractures. The right knee had a stable intraarticular fracture coupled with Kirschner wire immobilization while the left knee was not surgically manipulated. The rabbits (n=6) were sacrificed two weeks later, and the ACL, MCL, posterior joint capsule and medial meniscus were obtained from both knees. Semiquantitative RT-PCR was used to evaluate relative mRNA expression of selected matrix molecules, growth factors and _-smooth muscle actin (_-SMA), a myofibroblast marker. Glyc-eraldehyde-3-phosphate dehydrogenase, a housekeeping gene, served as a normalization. Optical density measures of the gels were used for analysis. Statistical comparisons were made with a paired t-test. Statistical significance was p< 0.05. Relative mRNA expression was altered for six of seven molecules in the joint capsule, four of seven molecules in the ACL, and two of seven molecules for the MCL and meniscus. For the joint capsule, relative mRNA expression in the contracture capsule was 2-4x greater than the expression in the control capsules, except for TIMP one where the expression in the contracture capsule was 1/3 of the control capsules. As has been noted with other joint injuries (ligament instability), several structures in the joint display altered molecular expression as was found in this model of joint injury, post-traumatic joint contractures. Please contact author for tables and/or graphs

Purpose: The objective of the present study was to determine whether human mast cells can modify behavior of human elbow contracture capsule cells in an in vitro collagen gel contraction assay. Method: Posterior elbow joint capsule was obtained from a 38 year old man with a chronic (> 1 year) post-traumatic joint contracture. Joint capsule cells were isolated and suspended at a density of 2.5 x 105 cells/ml, and mixed with neutralized Collagen solution composed with 58% Vitrogen 100 purified collagen. Aliquots of collagen gel without cells, with only the human mast cell line, HMC-1 (2.5× 105), human capsule cells (2.5 × 105), human capsule cells (2.5 × 105) and an equal number of mast cells (1:1), or human capsule cells (2.5× 105) and 7.5× 105 mast cells (1:3) were then cast into wells tissue culture plate. The gels were maintained with 0.5 ml DMEM composed with 2% BSA and incubated at 37°C for 12 h for gelation to occur. After 12 hr initial culture, the gels were detached from the wall and the bottom of culture plate wells, and gel area was determined at 0h, 2h, 4h, 6h, 24h, 48h, and 72h Gel contraction studies were carried out on passage 6 and done in triplicate. The blocking assay to inhibit mast cell – joint capsule cell interaction employed antibodies to Stem Cell Factor (SCF) and c-kit. SCF (0.5, 1 or 10 microg/ml) and/or c-kit (0.05, 0.1 or1 microg/ml) were added individually or in combination (SCF 10 microg/ ml and c-kit 1 microg/ml only) to cells/collagen gel mixture before gel casting. The ratio of human capsule cells and HMC-1 were kept constant at 1:3 throughout the experiment. The inhibitory effect of SCF and c-kit antibodies on collagen gel contraction induced by human capsule cells and HMC-1 was expressed in percentage of gel areas at 24h post release. Inhibition effect (%) = 100% – [(gel size – c-kit or SCF gel size)/(blank gel size – JC:M gel size)x 100%]. Statistical analysis involved an ANOVA with posthoc Bonferroni correction. P < 0.001 was significant. Data are mean ± standard deviation. Results: Joint capsule cells were able to contract collagen gels in a time-dependent manner. This contraction was significantly enhanced in the presence of the HMC-1 cells in a dose dependent fashion (p < 0.001). HMC-1 cells were unable to contract the collagen gels by themselves. Experiments with antibodies to the mast cell – fibroblast direct cell-cell communication determinants SCF or c-kit showed inhibition of the enhanced contraction at 24 hours between 43 – 72%. Combining the highest dose of SCF and c-kit led to 82% inhibition. Conclusion: This study has shown that cells isolated from human elbow joint contracture capsules respond to mast cells in a collagen gel assay in a dose dependent manner. This study is consistent with our previous work which has shown that ketotifen, a mast cell stabilizer that prevents mast cell degranulation and liberation of factors, can reduce contracture severity in a rabbit model of post-traumatic joint contractures

Aims

The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

Introduction and Aims: With a great progress in bone regeneration, muscle is currently regarded as a largest limiting factor for successful limb lengthening leading to joint contractures and fractures of distraction regenerate. The purpose of this study was to evaluate muscle architectural changes and potential mechanisms of joint contractures during limb lengthening. Method: Nine mature goats underwent 20% unilateral tibial lengthening (0.25 mm x 3/day) and were sacrificed immediately upon completion of distraction. With the stifle (knee) and hock (ankle) joints fixed at similar angles, both limbs were disarticulated at the hip joint and submerged into 10% buffered formalin. Following tissue fixation, all tibial muscles were sequentially dissected and changes in muscle origin-to-incretion length, belly length, tendon length, myofibers length, and sarcomere length were analysed relative to the muscle measurements on the contralateral limb and bone lengthening. Muscle fiber length was assessed under stereoscopic magnification and sarcomere analysis was performed using laser diffraction. Results: Thirteen muscles were identified for each limb. Anterior compartment consisted of two longitudinal and four pennate muscles, whereas posterior compartment had one longitudinal and six pennate muscles. Origin-to-insertion length measurements showed disproportion between the amounts of muscle and bone length increase with muscle-to-bone lengthening ratio ranging from 0.2 to 1.0. When assessed separately, muscle belly stretched more substantially (range, 11–24%) than muscle tendon (range, 3–14%). Longitudinal muscles showed better compliance to limb lengthening than pennate muscles. Origin-to-insertion, muscle belly, and tendon length increase for longitudinal muscles averaged 15%, 21%, and 11%, respectively, whereas for pennate muscles these parameters averaged 10%, 15%, and 6%, respectively. Although anterior pennate muscles showed higher proportion of muscle length increase than posterior pennate muscles, this difference was not significant. Lengthening of muscle fibers varied greatly, ranging from 0% to 88%. Fiber length of posterior muscles increased tremendously (average, 42%). This was associated with comparable increase in sarcomere length (average, 39%). Anterior muscles showed only 10% lengthening of the fibers. However, 12% reduction in sarcomere length indicated addition of new sarcomeres in series to accommodate increase in fiber length. Conclusion: Different response of anterior and posterior muscles to distraction contributed greatly to the development of joint contractures. Posterior tibial muscles were predominantly pennate, larger in volume, and thus showed higher resistance to lengthening. Moreover, posterior muscle fibers incurred lengthening by sarcomere stretching, whereas anterior muscle fibers showed evidence of neosarcomerogenesis

The hypothesis is that cells isolated from capsules of joints with contractures will contract collagen gels at a faster rate when compared to cells obtained from capsules of joints free of contractures. Post-traumatic joint contractures were produced by removing cortical bone windows from the femoral condyles of three skeletally mature rabbits and immobilizing the knees for four weeks with a K-wire. The contralateral knees served as an unoperated control. At sacrifice, the posterior capsules were immediately placed in medium and the tissue was minced. Upon confluence, cells were trypsinised and gel contraction studies were carried out on passage four cells. Five x 105 cells/ml were mixed with 58% neutralised bovine collagen solution and five hundred microlitres of collagen gel/cells solution were then cast into wells of a tissue culture plate. Gelation occurred overnight at 37C in a humidified incubator containing 5% CO2. At cultured day zero, day one, day three, the gels were released from the well walls. The areas of the gel were measured using an image analyzer immediately after release (zero hour), and one hour, two hour, three hour and four hour post-release. The amount the collagen gels were contracted depended on the time of preincubation of cells and collagen before release and the source of the joint capsule cells. In general, increasing the time of preincubation heightened the contractile response of the cells. The collagen gel contraction was small for the day zero groups over the first four hours, but for the day three groups the rate of contraction was markedly increased. In all cases the collagen gel contraction was larger for the contracture capsule cells when compared to the control capsule cells. The patterns of the contraction over the four hours post release were similar for contracture and control groups. Cells from capsules of joints with post-traumatic contractures have intrinsically heightened in vitro contractile properties when compared to normal cells. Future work will determine whether the response is exaggerated to fibrotic stimuli such as TGF-beta1 in these capsule cells from post-traumatic joint contractures

Aims

As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA).

Aims

There are concerns regarding complications and longevity of total elbow arthroplasty (TEA) in young patients, and the few previous publications are mainly limited to reports on linked elbow devices. We investigated the clinical outcome of unlinked TEA for patients aged less than 50 years with rheumatoid arthritis (RA).

Introduction: The aim of this study was to identify the pattern of symptoms in patients presenting with synovial sarcoma, examine how these corresponded to the symptoms outlined by the NICE guidelines on the rapid referral of patients with a suspected sarcoma and spot factors that led to long delays in diagnosis. Methods: Early symptoms and the results of clinical and radiological investigation were reviewed along with the presumed diagnoses that had been made for 35 children. The total duration of symptoms was separated into patient delay and doctor delay. Results: Using the four clinical findings suggestive of sarcoma according to the NICE guidance, only half of the patients had one or more of them at the time of initial symptoms. The most common presentation was a painless mass (n=16), and in 10 children there was no mass identified. Seven patients had an inexplicable joint contracture, many having been extensively investigated unsuccessfully. The mean duration of symptoms before the diagnosis was made was 98 weeks (range 2 to 364). The mean number of doctors seen prior to referral was 3 (range 1–6) and for 15 patients the diagnosis was obtained after inadvertent excision. The factors associated with long duration of symptoms before diagnosis were knee and elbow location (p=0.0047) or periarticular location (p=0.01), absence of lump (p=0.016) or painful mass as early symptom (p=0.04), the presence of calcifications on x-rays (p=0.01) and a fixed joint contracture (p=0.0003). We could not show that delay in diagnosis led to a worse prognosis. Discussion: This paper highlights the sometimes bizarre symptoms associated with synovial sarcoma and hopefully this will increase awareness of the condition among relevant sections of the medical profession and help to reduce the delay in diagnosing these cases

We have analysed the pattern of symptoms in patients presenting with synovial sarcoma to identify factors which led to long delays in diagnosis. In 35 children, the early symptoms and the results of clinical and radiological investigation were reviewed, along with the presumed diagnoses. The duration of symptoms was separated into patient delay and doctor delay. Only half of the patients had one or more of the four clinical findings suggestive of sarcoma according to the guidance of the National Institute for Clinical Excellence at the onset of symptoms. Of the 33 children for whom data were available, 16 (48.5%) presented with a painless mass and in ten (30.3%) no mass was identified. Seven (21.2%) had an unexplained joint contracture. Many had been extensively investigated unsuccessfully. The mean duration of symptoms was 98 weeks (2 to 364), the mean patient delay was 43 weeks (0 to 156) and the mean doctor delay was 50 weeks (0 to 362). The mean number of doctors seen before referral was three (1 to 6) and for 15 patients the diagnosis was obtained after unplanned excision. Tumours around the knee and elbow were associated with a longer duration of symptoms and longer doctor delay compared with those at other sites. Delays did not improve significantly over the period of our study of 21 years, and we were unable to show that delay in diagnosis led to a worse prognosis. Our findings highlight the variety of symptoms associated with synovial sarcoma and encourage greater awareness of this tumour as a potential diagnosis in childhood

Introduction. Muscle stiffness and joint contractures are common complications of limb lengthening. Authors have demonstrated less permanent soft tissue complications with intramedullary lengthening than external fixation. Our aim was to evaluate the joint response following intramedullary femoral lengthening and need for physiotherapy and alteration to rate/rhythm of lengthening. Method. A retrospective review of documentation for all femoral Precice nails in our centre inserted between 2012 and 2017. This involved 98 nails (68 antegrade, 30 retrograde) in 88 patients (59 males, 29 females) with a mean age of 32 years (range 12–69 yrs). We excluded cases where there was no documentation regarding Range of Movement (ROM). Bilateral lengthenings were recorded as separate cases. This left 50 antegrade, 16 retrograde cases with hip ROM data and 55 antegrade, 26 retrograde cases with Knee ROM data. Results. Hip. In the antegrade group 20 cases (39%) developed no stiffness throughout treatment. ROM decreased in 61% (n=30) of cases and the median length at which this occurred was 3cm. Where a retrograde nail was inserted 62.5% of cases (n=10) maintained normal range of motion. The median length at which ROM decreased was 3.25cm, this occurred in 6 cases (37.5%). . Knee. Where the antegrade nail was inserted, 22 cases (40%) did not develop stiffness. There was reduced ROM in 33 cases (60%), occurring at a median distance of 2cm. The median distance at which reduced ROM occurred with the retrograde nails was 1.5cm, this occurred in 23 cases (88.5%). 3 cases did not develop stiffness. All cases regained full ROM. Conclusion. Although there was no permanent loss, Joint Stiffness still occurs with intramedullary limb lengthening and there remains the need for regular physiotherapy. There are no data from other institutions for comparison. Rehabilitation guidelines and a proforma to accurately monitor patients ROM throughout treatment have been developed

Purpose: To review the orthopaedic manifestations and document the results of surgical intervention. Material and Methods: A review of all 22 children currently attending a specialist scleroderma clinic was performed. Disease extent was measured in terms of percentage body surface area (BSA) affected and all orthopaedic abnormalities were documented. The outcome of surgical intervention was evaluated. Results: All children presented by the age of 12 and all but 2 had developed joint contractures of either the lower or upper limbs affecting function within 2yrs of diagnosis. Overall, lower limbs were more commonly affected than upper. Abdominal scleroderma led to a scoliosis in 75% of cases. The mean BSA affected was 35% (range 5-65%) with contractures more related to site of disease rather than extent. Pain was associated with lower limb contractures and loss of function with hand contractures. Limb length discrepancy (LLD) was common with a mean of 3cms (range 2-6.5cms). 8 children have had surgery. 7 developed wound healing problems. 50% of operations failed to correct the deformity and in a further 25% relapse has occurred. In the remaining 2 cases a good result was achieved. In addition, one epiphysiodesis has been performed and 3 are planned. Conclusions: This is the largest known review of children with linear scleroderma. Joint contractures are common but poorly managed by conservative methods alone. Surgical intervention is difficult but early defini-tive treatment is recommended with subsequent aggressive splinting during growth whilst the disease is active. LLD must be corrected

Purpose: The presence of hemarthrosis during joint injury is a potential inciting stimulus in the genesis of joint capsule fibrosis. Using a rabbit model of posttraumatic knee joint contracture, our hypothesis was that, bone marrow-derived elements of hemarthrosis rather than simply the presence of blood in the joint, trigger the induction of capsule fibrosis in post-traumatic joint contracture. Method: 35 Skeletally mature New Zealand White female rabbits (12–18 months old, 5.5 ± 0.5 kg) were randomly assigned to one of five groups: Immobilization-Only (IMO), Immobilization+ Bone Marrow (IMBM), Immobilization+ Peripheral Blood (IMPB), Bone Marrow-Only (BMO), and Controls. Surgeries: Immobilization groups had one knee joint fixed at full flexion with a Kirschner wire drilled through the tibia, passed posterior (extra-articular) to the knee joint and bent around the femur. Bone marrow groups had cortical windows removed from the non-articular cartilage portion of the medial and lateral femoral condyles. In the IMPB group, autologous peripheral venous blood was injected into the immobilized knee joint to recreate a non-traumatic hemarthrosis. The control group did not have any intervention. Joint angle measurements: After 8 weeks, rabbits were euthanized, all muscular tissue was removed and maximum extension angle of the joints with intact capsule was measured using a standard torque applied via a custom made rabbit knee gripping device attached to a MTS TestStar II. Each joint was cycled 5 times (0.2 Nm) and the average of 5 cycles was calculated. Statistical analysis consisted of a one-way ANOVA with posthoc Scheffe test (significance p < 0.05). Data are presented as mean +/ − standard deviation. Results: The IMBM (n=8) and IMPB (n=7) groups had significantly greater contractures (52 +/ − 12 and 58 +/ − 13 degrees, respectively) when compared to the BMO (n=7) and control (n=6) groups (32 +/ − 10 and 32 +/ − 13 degrees, respectively). The IMO group had average contracture measures of 44 +/ − 15 degrees. There was no statistically significant difference between the IMBM and IMPB groups. Conclusion: The present study showed differences in the contracture severity of the immobilized knees associated with hemarthrosis compared to other experimental and control groups. There does not appear to be a difference whether the hemarthrosis arose from a fracture (bone marrow) versus peripheral blood in rabbits. Future work will look at reversibility of contractures in the various groups. Studies on the joint capsule will evaluate myofibroblast numbers in concert with mast cell and neuropeptide distribution based on our previous work. Such knowledge will aid the prevention and treatment of the difficult and disabling problem of contracture formation after joint injury

Aims

The aim of this study was to determine the consensus best practice approach for the investigation and management of children (aged 0 to 15 years) in the UK with musculoskeletal infection (including septic arthritis, osteomyelitis, pyomyositis, tenosynovitis, fasciitis, and discitis). This consensus can then be used to ensure consistent, safe care for children in UK hospitals and those elsewhere with similar healthcare systems.

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The aim of this retrospective cohort study was to assess and investigate the safety and efficacy of using a distal tibial osteotomy compared to proximal osteotomy for limb lengthening in children.

Introduction: Therapeutic bone marrow transplantation has increased survival in Hurler syndrome, but the effects on musculoskeletal development remain unclear. Long term reports on mobility are poor, with many patients gradually losing walking ability in later childhood secondary to hip subluxation and joint contractures. As previous cohorts are small, data is limited. Methods: We detail the follow up of twenty patients over a mean of 94 months (range 1 – 17.4 years). Radiographs were assessed for hip dysplasia using acetabular angle of Sharp, centre edge angle of Wiberg and tibiofemoral shaft angle. Clinical examination was performed at an annual multidisciplinary assessment by one clinician and compared against age matched controls. 3D gait analysis was performed on eight older children, and deviance in kinematic variables was plotted against controls with Mann-Whitney U test for statistical analysis. Results: All patients demonstrated characteristic ace-tabular dysplasia. Fourteen patients have undergone containment surgery at a mean of 4.4 years. Innominate osteotomy is an essential part of this. Mean preoperative acetabular angle was reduced from 34 ± 4° to 22 ± 3°. Femoral head containment is maintained, with mean centre edge angle in older patients 39 ± 7°. Genu valgum is observed early, and five patients underwent medial epiphyseal stapling at a mean of 7.8 years, decreasing tibiofemoral angle by a mean of 8.0°. All patients are currently independently mobile, with restriction of internal hip rotation being the only significant clinical finding (P< 0.001). Joint contractures were not noted. Walking speed and stride length were comparable to controls, but endurance is reduced by about one quarter. Gait analysis demonstrates a characteristic pattern, with anterior pelvic tilt secondary to thoracolumbar gibbus, relative hip flexion throughout the gait cycle, valgus knees and compensatory pronated feet; all measured deviations were significant (P< 0.001). Conclusions This large group maintained successful hip containment and good mobility throughout childhood. Innominate osteotomy alone has been used recently. Despite plain film appearance, genu valgum is a functional problem in gait, and we would anticipate greater use of corrective stapling in the future. This is the first report of gait analysis in Hurler syndrome, and features specific to the condition are described

Between 1990 and 2001, 24 children aged between 15 months and 11 years presented with late orthopaedic sequelae after meningococcal septicaemia. The median time to presentation was 32 months (12 to 119) after the acute phase of the disease. The reasons for referral included angular deformity, limb-length discrepancy, joint contracture and problems with prosthetic fitting. Angular deformity with or without limb-length discrepancy was the most common presentation. Partial growth arrest was the cause of the angular deformity. Multiple growth-plate involvement occurred in 14 children. The lower limbs were affected much more often than the upper. Twenty-three children underwent operations for realignment of the mechanical axis and limb-length equalisation. In 15 patients with angular deformity around the knee the deformity recurred. As a result we recommend performing a realignment procedure with epiphysiodesis of the remaining growth plate when correcting angular deformities

Introduction. Pelvic posterior tilt change (PPTC) after THA is caused by release of joint contracture and degenerative lumbar kyphosis. PPTC increases cup anteversion and inclination and results in a risk of prosthesis impingement (PI) and edge loading (EL). There was reportedly no component orientation of fixed bearing which can avoid PI and EL against 20°PPTC. However, dual mobility bearing (DM) has been reported to have a large oscillation angle and potential to withstand EL without increasing polyethylene (PE) wear against high cup inclination such as 60∼65°. Objective. The purpose of this study was to investigate the optimal orientation of DM-THA for avoiding PI and EL against postoperative 20°PPTC. Methods. Our study was performed with computer tomography -based three-dimensional simulation software (ZedHip. LEXI co. Japan). The CT data of hip was derived from asian typical woman with normal hips. Used prosthesises were 50mm cup and 42mm outer head of modular dual mobility system and Accolade II 127°(stryker). Femoral coordinate system was retrocondylar plane with z-axis from trochanteric fossa to intercondylar notch. Cup orientation was described as anatomical definition. The safe zone was calculated by the required hip range of motion which was defined as 130°flexion, 40°extension, 30°external rotation, and 50°internal rotation with 90°flexion and the maximum inclination of DM cup which was 60°in consideration of withstanding EL. Cup orientations withstanding 20°PPTC were defined as the primary cup orientation which changes consistently within the safe zone with the match of 20°PPTC. And among them cup orientation with lowest inclination was defined as the optimal cup orientation. result. The optimal orientations could be identified only within stem anteversion from 15°to 40°. The relationship between the optimal cup orientation and stem anteversion could be automatically identified. The correlation between stem anteversion and cup anteversion was linearly distributed and could be expressed as an approximated line of the formula that (stem anteversion)+(cup anteversion)=36.8. And likewise the relationship between stem anteversion and cup inclination was curved-linerly distributed and could be expressed as an approximated curved line of the formula that (cup inclination)=0.04(stem anteversion). 2. 2.18(stem anteversion)+74.8. Cup orientation calculated by the Widmer's combined anteversion theory is easily deviated from the safe zone by PPTC. The optimal cup orientation calculated in this study could be set more inclination and retroversion than it calculated by the Widmer's theory in contribution of large oscillation angle and admissibility of high inclination cup setting of DM. Therefore it could be possible to withstand 20°PPTC. Conclusion. Performing THA with considering postoperative PPTC is necessary for good long term outcome without dislocation and PE wear. The solution for 20°PPTC after THA is to apply dual mobility bearing and the formula of combined orientation theory calculated in this study

Aims

Outcomes of current operative treatments for arthrofibrosis after total knee arthroplasty (TKA) are not consistently positive or predictable. Pharmacological in vivo studies have focused mostly on prevention of arthrofibrosis. This study used a rabbit model to evaluate intra-articular (IA) effects of celecoxib in treating contracted knees alone, or in combination with capsular release.

Dupuytren's disease is often disabling and traditionally has been managed with various surgical methods, with recurrence rates up to 50 %. Recently clostridial collagenase injection has been licensed for use in the NHS. We prospectively analysed the results of clostridial collagenase injection in 62 patients with varying degrees of Metacarpo phalangeal (MCP) and Proximal interphalangeal (PIP) joint contractures. There were 48 males and 14 females with an average age of 66 years. The average MCPJ and PIPJ deformities were 33 and 17 degrees respectively. Following the infiltration and subsequent manipulation under local anaesthetic and night splinting for 3 months, patients were followed up at 4 weeks and 6 months. Deformities persisted in 5 patients and later required surgical correction. MCPJ deformities were more amenable for correction than PIPJ and in those with recurrence. The average residual deformity was 7 degrees. Common complications include bruising, swelling, pain not responding to routine analgesia, lymphangitis and skin break in some but none required any additional interventions. 14 patients had completed 6 month follow up and there was no recurrence. Subjective assessment through questionnaires revealed high patient satisfaction rate with early return to work within 1 week in most patients. Patients with previous operations preferred injections over operative correction. Collagenase injections are effective in deformity correction with higher satisfaction rate and low morbidity. Early results are encouraging but long term follow up is required to assess recurrence rates

Aims

With novel promising therapies potentially limiting progression of Dupuytren’s disease (DD), better patient stratification is needed. We aimed to quantify DD development and progression after seven years in a population-based cohort, and to identify factors predictive of disease development or progression.

Introduction. Knee osteoarthritis (OA) is a major contributor to disability in seniors and affecting millions of people around the world. Its main problem and the biggest factor in the disability of patients is pain. Pain renders patient inactive and develops lower extremity muscle wasting and worsens patient status adversely. However no radical solution existed until now. Recently I discovered a very valid manipulative technique (Squeeze-hold) for OA knee. This study presents the one-year follow-up data (three cases) by this treatment. Methods. Subjects. The subjects were three severe knee OA patients who had their data collected for 12 months after having a treatment. Treatment (squeeze-hold): The lower limb muscles (all muscles attached to the knee joint) were squeezed and held by hand. Each squeeze was performed in linear sequence all the way through the lower limbs. The squeezes were held for 20 seconds. This treatment was performed on a weekly basis. Evaluation: The conditions of the OA were evaluated using a Kellgren-Lawrence Grading Scale. Visual analogue scale as indicator of pain and Japanese Knee Osteoarthritis Measure as indicator of the activity restriction were recorded every month for a year. Results. In all three cases, OA knee pain and ADL were gradually improved by sustained once-a-week treatment. The daily activities were gradually increased. After a year, the pain passed approximately away. In case 1 and 2, a limitation in ROM did not show a marked improvement and joint contracture remained. Discussion. Squeeze-hold therapy that is approach to lower-limb muscles relieved OA knee pain. It is suggested by the fact that lower-limb muscles is responsible for the pain. And the physical activity of knee OA patient increases with decreasing pain effected by Squeeze-hold therapy. This increase in physical activity provides increase in joint movement and it lead to improve articular metabolism. Cyclical loading increases chondrocyte activity. Additionally, It inhibits the release of matrix metalloproteinase, pro-inflammatory mediators and shear stress-induced nitric oxide that induces chondrocyte apoptosis. And further, this increased physical activity improves muscle-strengthening of the lower extremity. It is plausible that these effects may continuously lead to decreased pain and improved ADL. A primary pain in knee OA can be attributed to inflammation of knee joint capsule or within knee joint capsule. And the pain leads to muscular hypertonicity thereby a bigger secondary pain develops in the muscles. Decreased physical activity due to the pain worsens pathological condition to induce greater pain. By this means, there might be formed pain-deterioration chain. Squeeze-hold therapy reduces the myogenic pain and cut the pain-deterioration chain. However, ROM could not improve though the pain and ADL activity imploved. This treatment ought to be performed before the formation of articular contracture. The results indicate Squeeze-hold treatment for lower-limb muscles might improves OA knee pain and limited ADL. However, this study had only three cases. Further research efforts are needed to identify the adaptation to diverse clinical symptoms knee OA

We describe the treatment of three boys with cavernous lymphangioma of the legs. The suggested guidelines for treatment are extensive surgical resection, although complete resection is usually impossible, and approximately two weeks after the operation aspiration of serous fluid which has accumulated at the operation site, followed by injection of OK-432 (Picibanil). There was pyrexia and local inflammation for several days but the accumulation of serous fluid disappeared after the injection. There were no complications with no recurrence, joint contracture, or pain during a mean follow-up of 48 months (24 to 72). We conclude that an injection of OK-432 after surgical resection of cavernous lymphangioma of the legs in children is an effective treatment

In developed countries, children with cerebral palsy are treated from the time of diagnosis. This is usually not the case in developing countries where such patients often present at an age when it is traditionally believed that if walking has not already commenced, it is unlikely to. This study reports the outcome of the surgical treatment of 85 spastic diplegic patients at a mean of 8.5 years (5 to 12). All presented as untreated non-walkers and had achieved sitting balance by the age of five to six years. They underwent single-event multilevel surgery followed by physiotherapy and orthotic support. For outcome assessment, a modified functional walking scale was used at a mean of 3.5 years (2 to 5) post-operatively. At all levels, static joint contractures had resolved almost completely. All patients improved and became walkers, 18 (21.2%) as exercise, 39 (45.9%) as household and 28 (33%) as community walkers. This study shows that children with cerebral palsy who cannot walk and have not been treated can be helped by single-event multilevel surgery, provided that inclusion criteria are followed and a structural, supervised rehabilitation programme is in place

Haemophilia care has steadily improved over the years and especially so during the last decade. The routine use of prophylactic treatment has undoubtedly resulted in a significant improvement in the life-style, quality of life and life expectancy of these patients, and bodes well for the future. The knee is the most common joint affected in patients with severe haemophilia (approx 50%) and despite best efforts there is still a group of young adults who have a severe degree of knee joint destruction as a result of repeated articular bleeding episodes during their early years. The indications for operation are primarily disabling pain that is unresponsive to medical treatment. Deformity and poor functional range of motion, particularly a severe flexion contracture of the knee, are relative indications and may in themselves justify joint replacement. Equally joint contractures and flexion deformity pose various surgical challenges for the surgeon. The introduction of continuous replacement clotting factor has facilitated the operation and in our experience has reduced the complications of TKR. We have found that it permits earlier rehabilitation and in our present series the outcome in this group of patients almost comparable to TKR performed in the general population

We treated 13 children with histologically confirmed cystic tuberculosis of bone. Ten had solitary cystic lesions and three had the multicystic form. Signs and symptoms were related mainly to the joint adjacent to the cyst. Most lesions were in the metaphyses of long bones. They were radiolucent, round or oval, and resembled pyogenic infections, aneurysmal and simple bone cysts, cartilaginous tumours or osteoid osteoma. Only two of the children had pulmonary tuberculosis. The Mantoux skin test was negative in four children and the ESR was normal in five. Curettage followed by anti-tuberculosis therapy for one year resulted in good healing, but two children had residual joint contractures. Biopsy should be taken from the cystic area rather than from the synovium when a joint is involved

Aims

To assess the characteristic clinical features, management, and outcome of patients who present to orthopaedic surgeons with functional dystonia affecting the foot and ankle.

Arthrogryposis multiplex congenita (AMC) is a rare disease with multiple joint contractures. It is widely believed that bilaterally dislocated hips should not be reduced since movement is satisfactory and open reduction has had poor results. Since 1977 we have performed a new method of open reduction using an extensive anterolateral approach on ten hips in five children with AMC. The mean age at surgery was 31.5 months (17 to 64) and the mean follow-up was 11.8 years (3.8 to 19.5). At the final follow-up all children walked without crutches or canes. Two managed independently, one required a long leg brace and two had short leg braces because of knee and/or foot problems. The clinical results were good in eight hips and fair in two and on the Severin classification seven hips were rated as good (group I or group II). We recommend the extensive anterolateral approach for unilateral or bilateral dislocation of the hip in children with arthrogryposis or developmental dislocation of the hip

Purpose: To determine if cells isolated from the rabbit joint capsule in post-traumatic joint contractures have altered responses to stimuli and inhibitors. Method: The right knee of three rabbits had cortical windows removed from the femoral condyles followed by 4 weeks of immobilization, a recently developed model of post-traumatic contractures. The contralateral knee served as an unoperated control. Primary cells (2.5 × 105 cells/ml) isolated from the posterior capsule were mixed with neutralized bovine collagen solution and then cast into tissue culture plate wells. Gelation occurred overnight and then the cells were treated with 1% serum replacement (control), 10 ng/mL TGF-beta1, and the TGF-beta1 receptor kinase inhibitor SB431542 at 10 microM or 0.1 microM. Gel contraction was measured at 24 post release from the edges of the well using captured images of the gels and computer software. Results: In all groups the contracture (injured) knees displayed significantly greater collagen gel contraction than control capsule cells. The addition of the TGF-beta1 increased, while SB431542 at the higher dose decreased, the extent of contraction by contracture and control cells. The TGF-beta1 contraction effect was neutralized by the addition of the inhibitor at the higher dose. In terms of sensitivity to the manipulations, the contracture capsule cells had greater responses to the stimulant and inhibitor. Conclusion: This work is significant as this is the first description of joint capsule cell properties. In post-traumatic contractures, these cells have an intrinsically increased contraction ability at baseline conditions (serum replacement), and these cells also have heightened responses to TGF-beta1 and the TGF-beta1 receptor kinase inhibitor SB431542, a known pathway associated with fibrosis. These results support future work modifying this pathway directly, or by manipulating cells that liberate TGF-beta1. One such strategy would be to prevent mast cells from degranulating as they are a source of TGF-beta1 and other profibrotic growth factors, cytokines and enzymes

Aims

In the UK, fasciectomy for Dupuytren’s contracture is generally performed under general or regional anaesthetic, with an arm tourniquet and in a hospital setting. We have changed our practice to use local anaesthetic with adrenaline, no arm tourniquet, and perform the surgery in a community setting. We present the outcome of a consecutive series of 30 patients.

Despite the impressive advancements in prenatal planning and assessment, obstetrical brachial plexus palsy remains an unfortunate consequence of difficult childbirth. Although the majority of infants with plexopathy recover with minor or no residual functional deficits, a number of children do not regain sufficient limb function and develop significant functional limitations, bony deformities and joint contractures. Recent developments in the technique of microsurgical reconstruction of peripheral nerve injuries proved to be effective in selected cases of children with obstetrical brachial plexus injury. Many of these children and those who were defined as having minor injury will remain with considerable functional limitation and deserve late orthopaedic reconstruction. Based on that, we developed a multidisciplinary Brachial Plexus clinic gathering a microsurgeon, a pediatric orthopaedic surgeon, an electrophysiologist clinician, physiotherapists and occupational therapist in order to assess and evaluate these children. A total of 105 children were seen and followed up in our clinic during the last 2 years. Most of these children were referred to our clinic from other centers and from physiotherapists treating these children on an out-patient basis. We report the orthopaedic reconstruction operations performed in 9 cases of residual functional disabilities in children born with obstetric palsy. 4 patients had latissimmus dorsi and teres major transfer. 2 patients had derotation osteotomy of the humerus. 1 patient had Steindler flexorplasty of the elbow. 2 patients had open reduction and capsulorrhapy for a dislocated shoulder. Video assessment of these children was performed before and after the operation. Function was also analyzed before and after operation by a physiotherapist and an occupational therapist. Significant functional improvement was achieved, to the satisfaction of patients and parents

Patients with hemiplegic cerebral palsy walk with a well recognised characteristic gait pattern. They also commonly have a significant leg length discrepancy which is less well appreciated. The typical equinus gait in these patients is assumed to be an integral part of the disease process of spasticity and a tendency to develop joint contractures. However an alternative explanation for the presence of an equinus deformity may be that it is a response to the development of a significant leg length discrepancy in these patients. The development of such an equinus deformity would have the effect of functionally lengthening the short hemiplegic leg. We set up a study to examine the correlation between leg length discrepancy and equinus deformity. We reviewed the gait analyses and clinical examinations of 183 patients with hemiplegic cerebral palsy. While 22% had no significant leg length discrepancy, 65% had a measured discrepancy of greater than 1cm. There was a linear correlation between age and limb length discrepancy. We also found that there was a linear relationship between leg length discrepancy and ankle equinus at the point of ground contact. We propose that the equinus deformity seen in the hemiplegic cerebral palsy patient is multifactorial and is related not only to the disease state but also to the presence of leg length discrepancy. The equinus deformity functionally lengthens the short hemiplegic leg. Indeed it may represent an attempt by these patients to functionally equalise their leg lengths. This factor must be taken into account when considering correction of an equinus deformity in patients with hemiplegic cerebral palsy in order to avoid either recurrence of the deformity or the production of functionally unequal leg lengths. We have also highlighted the presence of significant shortening of the hemiplegic leg in these patients