Simon Benedict Roberts

Dexamethasone-induced expression of the glucocorticoid response gene lipocalin 2 in chondrocytes.

Glucocorticoids (GC) are commonly used anti-inflammatory drugs, but long-term use can result in marked growth retardation in children due to their actions on growth plate chondrocytes. To gain an insight into the mechanisms involved in GC-induced growth retardation, we performed Affymetrix microarray analysis of the murine chondrogenic cell line ATDC5, incubated with 10(-6) M dexamethasone (Dex) for 24 h. Downregulated genes included secreted frizzled-related protein and IGF-I, and upregulated genes included serum/GC-regulated kinase, connective-tissue growth factor, and lipocalin 2. Lipocalin 2 expression increased 40-fold after 24-h Dex treatment. Expression increased further after 48-h (75-fold) and 96-h (84-fold) Dex treatment, and this response was Dex concentration dependent. Lipocalin 2 was immunolocalized to both proliferating and hypertrophic growth plate zones, and its expression was increased by Dex in primary chondrocytes at 6 h (3-fold, P < 0.05). The lipocalin 2 response was blocked by the GC-receptor antagonist RU-486 and was increased further by the protein synthesis blocker cycloheximide. Proliferation in lipocalin 2-overexpressing cells was less than in control cells (49%, P < 0.05), and overexpression caused an increase in collagen type X expression (4-fold, P < 0.05). The effects of lipocalin 2 overexpression on chondrocyte proliferation (64%, P < 0.05) and collagen type X expression (8-fold, P < 0.05) were further exacerbated with the addition of 10(-6) M Dex. This synergistic effect may be explained by a further increase in lipocalin 2 expression with Dex treatment of transfected cells (45%, P < 0.05). These results suggest that lipocalin 2 may mediate Dex effects on chondrocytes and provides a potential novel mechanism for GC-induced growth retardation.

Circulating antibodies to lung protein(s) in patients with cryptogenic fibrosing alveolitis.

BACKGROUND--It has been hypothesised that cryptogenic fibrosing alveolitis has an immunological pathogenesis mediated by T lymphocytes. It is, however, recognised that patients may show dysregulation of the humoral immune system and that the presence of large numbers of B lymphocytes in open lung biopsies may be associated with a poor prognosis. Evidence of a role for the humoral immune system in the pathogenesis of cryptogenic fibrosing alveolitis has been suggested, but attempts to demonstrate circulating immunoglobulin to antigen within the lung have been inconclusive. METHODS--Plasma samples from 22 patients with cryptogenic fibrosing alveolitis, 22 patients with sarcoidosis, and 17 healthy controls were screened by SDS-PAGE and Western blotting for the presence of autoantibodies to lung proteins derived from cryptogenic fibrosing alveolitis, sarcoid and control lung tissue, as well as four normal non-pulmonary tissues. Possible site(s) of target protein(s) within the lung tissue were identified by immunohistochemical examination using IgG purified from the plasma of six patients and two controls. RESULTS--Eighteen of the plasma samples from patients with cryptogenic fibrosing alveolitis had reactive IgG to lung protein(s) in the 70-90 kDa molecular weight range compared with five of 18 plasma samples from patients with sarcoidosis and one of 17 controls. Plasma from patients with cryptogenic fibrosing alveolitis recognised antigen(s) of the same molecular weight in control and sarcoid lung tissue, but not non-pulmonary tissues, with a similar frequency. Immunohistochemical staining of cryptogenic fibrosing alveolitis biopsy material using IgG purified from plasma samples from patients with cryptogenic fibrosing alveolitis, but not control samples, revealed fine linear positivity in the lung parenchyma in a pattern suggestive of reaction with alveolar lining cells. The pattern was cytoplasmic/membranous and not nuclear. CONCLUSIONS--Patients with cryptogenic fibrosing alveolitis have a high frequency of plasma IgG autoantibodies to protein(s) within lung tissue associated with alveolar lining cells. This is believed to be the site where immunological injury occurs in cryptogenic fibrosing alveolitis, but the significance of these antibodies to the aetiology and pathogenesis is as yet unclear.

The natural history of primary anterior dislocation of the glenohumeral joint in adolescence

The natural history of primary anterior dislocation of the glenohumeral joint in adolescent patients remains unclear and there is no consensus for management of these patients. The objectives of this study were to report the natural history of primary anterior dislocation of the glenohumeral joint in adolescent patients and to identify the risk factors for recurrent dislocation. We reviewed prospectively-collected clinical and radiological data on 133 adolescent patients diagnosed with a primary anterior dislocation of the glenohumeral joint who had been managed non-operatively at our hospital between 1996 and 2008. There were 115 male (86.5%) and 18 female patients (13.5%) with a mean age of 16.3 years (13 to 18) and a mean follow-up of 95.2 months (1 to 215). During follow-up, 102 (absolute incidence of 76.7%) patients had a recurrent dislocation. The median interval between primary and recurrent dislocation was ten months (95% CI 7.4 to 12.6). Applying survival analysis the likelihood of having a stable shoulder one year after the initial injury was 59% (95% CI 51.2 to 66.8), 38% (95% CI 30.2 to 45.8%) after two years, 21% (95% CI 13.2 to 28.8) after five years, and 7% (95% CI 1.1 to 12.9) after ten years. Neither age nor gender significantly predicted recurrent dislocation during follow-up. We conclude that adolescent patients with a primary anterior dislocation of the glenohumeral joint have a high rate of recurrent dislocation, which usually occurs within two years of their initial injury: these patients should be considered for early operative stabilisation.

CD4+ and CD8+ T‐lymphocyte scores cannot reliably predict progression in patients with benign prostatic hyperplasia

To determine whether the density of CD4+ and CD8+ T‐lymphocytes in a transrectal ultrasonography (TRUS) biopsy of the prostate can be used to predict the progression of lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia (BPH).

Thoracolumbar kyphoscoliosis with unilateral subluxation of the spine and postoperative lumbar spondylolisthesis in Hunter syndrome.

Surgical correction for kyphoscoliosis is increasingly being performed for patients with mucopolysaccharidosis (MPS). Reported case series have predominantly included patients with Type I (Hurler) and Type IV (Morquio) MPS. To their knowledge, the authors describe the first case report of surgical management of thoracolumbar kyphoscoliosis in Hunter syndrome (MPS Type II) and the rare occurrence of lumbar spondylolisthesis following surgical stabilization. A 12-year-old boy with Hunter syndrome presented with severe thoracolumbar kyphoscoliosis and no associated symptoms. Spinal radiographs demonstrated kyphosis of 48° (T11-L3) and scoliosis of 22° (T11-L3) with an anteriorly hypoplastic L-1 vertebra. The deformity progressed to kyphosis of 60° and scoliosis of 42° prior to surgical intervention. Spinal CT scans identified left T12-L1 facet subluxation, causing anterior rotatory displacement of the spine proximal to L-1 and bilateral L-5 isthmic spondylolysis with no spondylolisthesis. A combined single-stage anterior and posterior instrumented spinal arthrodesis from T-9 to L-4 was performed. Kyphosis and scoliosis were corrected to 4° and 0°, respectively. Prolonged ventilator support and nasogastric feedings were required for 3 months postoperatively. At 2.5 years following surgery, the patient was asymptomatic, mobilizing independently, and had achieved a solid spinal fusion. However, he had also developed a Grade II spondylolisthesis at L4-5; this was managed nonoperatively in the absence of symptoms or further deterioration of the spondylolisthesis to the 3.5-year postoperative follow-up visit. Satisfactory correction of thoracolumbar kyphoscoliosis in Hunter syndrome can be achieved by combined anterior/posterior instrumented arthrodesis. The risk of developing deformity or instability in motion segments adjacent to an instrumented fusion may be greater in patients with MPS related to the underlying connective tissue disorder.

Factors influencing the evaluation and management of neuromuscular scoliosis: A review of the literature

Neuromuscular scoliosis (NMS) is the second most prevalent spinal deformity (after idiopathic scoliosis) and is usually first identified during early childhood. Cerebral palsy (CP) is the most common cause of NMS, followed by Duchenne muscular dystrophy (DMD). Progressive spinal deformity causes difficulty with daily care, walking and sitting, and can lead to back and rib pain, cardiac and pulmonary complications, altered seizure thresholds, and skin compromise. Early referral to specialist spinal services and early diagnosis of NMS is essential to ensure appropriate multidisciplinary patient management. The most important goals for patients are preservation of function, facilitation of daily care, and alleviation of pain. Non-operative management includes observation or bracing for less severe and flexible deformity in young patients as a temporising measure to provide postural support. Surgical correction and stabilisation of NMS is considered for patients with a deformity >40-50°, but may be performed for less severe deformity in patients with DMD. Post-operative intensive care, early mobilisation and nutritional supplementation aim to minimise the rate of post-surgical complications, which are relatively common in this patient group. However, surgical management of NMS is associated with good long-term outcomes and high satisfaction rates for patients, their relatives and carers.

The development and validation of a scoring system for shoulder injuries in rugby players

Background Shoulder injuries are relatively common among professional rugby players and result in a large proportion of days absent from training and competition. No instrument exists that is designed and validated to assess function or outcome following therapeutic interventions in rugby players sustaining shoulder injuries. The objective was to develop and validate an athlete-reported scoring system to assess shoulder function in rugby players following shoulder injuries. Methods Potential items for the scoring system were identified by a literature review of shoulder-specific scoring systems (n=46), and by interviewing professional rugby players (n=38) and medical staff (n=12). Redundant and clinician-assessed items were excluded. A second set of interviews with rugby players (n=8) determined the frequency importance product (FIP) of potential items. The 20 items with the highest FIPs were selected for the provisional Rugby Shoulder Score (RSS) that was tested for internal consistency and reliability by administering to rugby players with stable shoulder injuries (n=11). Results The literature review and interviews identified 575 items, of which 105 items were neither clinician-assessed nor redundant. Twenty items with the highest FIPs were selected for the RSS. The RSS demonstrated excellent internal consistency (Cronbachs α=0.96) and reliability (intraclass correlation coefficient= 0.941, paired student t test p>0.05). Conclusions A reliable athlete-reported scoring system for assessing shoulder injuries in rugby players has been developed that incorporates the most important factors for rugby players recovering from shoulder injuries. Further prospective testing of the instrument is being undertaken to determine its discriminative and evaluative functions and construct validity.

Surgery performed by supervised registrars does not adversely affect medium-term functional outcomes after total knee replacement

INTRODUCTION Although total knee arthroplasty (TKA) is an index procedure for orthopaedic registrars, there is a lack of published research as to the effects of surgery when performed by supervised trainees. The aim of this study was to compare functional outcomes up to five years after primary TKA performed by consultants and trainee surgeons. METHODS A retrospective analysis was conducted of prospectively collected data for 609 consecutive patients (339 female, 270 male) undergoing TKA. Patients were assessed preoperatively as well as at 18 months, three years and five years postoperatively, and American Knee Society objective knee and functional scores (AKSK and AKSF) were recorded. RESULTS Surgery was performed by a consultant in 465 cases and a supervised trainee in 144 cases. There were no significant differences between the two groups in preoperative patient characteristics, operative time (p=0.15), transfusion rates (p=0.84), length of stay (p=0.98), manipulation under anaesthesia (p=0.69), or mortality rates at one year (p=0.73) or five years (p=0.81). Postoperatively, the median magnitude of improvement in AKSK (48 points for consultant group vs 45 points for trainee group, p=0.74) and in AKSF (both groups 15, p=0.995) was similar between the groups. AKSK and AKSF scores were similar at all timepoints up to five years following surgery, and there was no difference in the median range of motion (both groups 100°, IQR: 18°) at five years (p=0.43). CONCLUSIONS TKA performed by supervised registrars gives functional outcomes that are equivalent to consultant performed TKA, without affecting postoperative range of movement, or increasing operative time, length of stay or transfusion rates. Rates of postoperative MUA and mortality are also comparable.

Thoracolumbar kyphosis in patients with mucopolysaccharidoses: clinical outcomes and radiological factors predictive of progressive deformity.

AIMS Clinical and radiological data were reviewed for all patients with mucopolysaccharidoses (MPS) with thoracolumbar kyphosis managed non-operatively or operatively in our institution. METHODS In all 16 patients were included (eight female: eight male; 50% male), of whom nine had Hurler, five Morquio and two Hunter syndrome. Six patients were treated non-operatively (mean age at presentation of 6.3 years; 0.4 to 12.9); mean kyphotic progression +1.5(o)/year; mean follow-up of 3.1 years (1 to 5.1) and ten patients operatively (mean age at presentation of 4.7 years; 0.9 to 14.4); mean kyphotic progression 10.8(o)/year; mean follow-up of 8.2 years; 4.8 to 11.8) by circumferential arthrodesis with posterior instrumentation in patients with flexible deformities (n = 6). RESULTS In the surgical group (mean age at surgery of 6.6 years; 2.4 to 16.8); mean post-operative follow-up of 6.3 years (3.5 to 10.3), mean pre-operative thoracolumbar kyphosis of 74.3(o) (42(o) to 110(o)) was corrected to mean of 28.6(o) (0(o) to 65(o)) post-operatively, relating to a mean deformity correction of 66.9% (31% to 100%). Surgical complications included a deep wound infection treated by early debridement, apical non-union treated by posterior re-grafting, and stable adjacent segment spondylolisthesis managed non-operatively. Thoracolumbar kyphosis > +38(o) at initial presentation was identified as predicting progressively severe deformity with 90% sensitivity and 83% specificity. DISCUSSION This study demonstrates that severe thoracolumbar kyphosis in patients with MPS can be effectively treated by circumferential arthrodesis. Severity of kyphosis at initial presentation may predict progression of thoracolumbar deformity. Patients with MPS may be particularly susceptible to post-operative complications due to the underlying connective tissue disorder and inherent immunological compromise. TAKE HOME MESSAGE Clinical and radiological data were reviewed for all patients with mucopolysaccharidoses with thoracolumbar kyphosis managed non-operatively or operatively in our institution.

Basic hip arthroplasty and basic knee arthroplasty

The basic hip arthroplasty and basic knee arthroplasty courses are two separate courses organised by the University of Dundee’s Cuschieri Skills Centre and run at various locations in the United Kingdom. This report relates to the courses run at the Royal College of Surgeons of Edinburgh. The courses are held on consecutive days and have similar daily programmes. The courses are targeted at specialty trainees years 1-4 interested in orthopaedics who wish to further their understanding of the indications for total hip and knee arthroplasty and the applied anatomy and basic science. These courses would also be appropriate for people who want to become familiar with implant options and surgical techniques, and to develop practical skills in performing total hip and knee arthroplasty. I enrolled …