Clare Darrah

The role of chondrocyte senescence in osteoarthritis

Replicative senescence occurs when normal somatic cells stop dividing. Senescent cells remain viable, but show alterations in phenotype, e.g. altered expression of matrix metalloproteinases (MMPs); these enzymes are known to be involved in cartilage destruction. It is assumed that cells deplete their replicative potential during aging, and age is a major risk factor for osteoarthritis (OA). Therefore, we hypothesized that chondrocytes in aging or diseased cartilage become senescent with associated phenotypic changes contributing to development or progression of OA.

Early clinical failure of the Birmingham metal-on-metal hip resurfacing is associated with metallosis and soft-tissue necrosis

The rate and mode of early failure in 463 Birmingham hip resurfacings in a two-centre, multisurgeon series were examined. Of the 463 patients two have died and three were lost to follow-up. The mean radiological and clinical follow-up was for 43 months (6 to 90). We have revised 13 resurfacings (2.8%) including seven for pain, three for fracture, two for dislocation and another for sepsis. Of these, nine had macroscopic and histological evidence of metallosis. The survival at five years was 95.8% (95% confidence interval (CI) 94.1 to 96.8) for revision for all causes and 96.9% (95% CI 95.5 to 98.3) for metallosis. The rate of metallosis related revision was 3.1% at five years. Risk factors for metallosis were female gender, a small femoral component, a high abduction angle and obesity. We do not advocate the use of the Birmingham Hip resurfacing procedure in patients with these risk factors.

Early failure of the Ultima metal-on-metal total hip replacement in the presence of normal plain radiographs

Metal-on-metal total hip replacement has been targeted at younger patients with anticipated long-term survival, but the effect of the production of metal ions is a concern because of their possible toxicity to cells. We have reviewed the results of the use of the Ultima hybrid metal-on-metal total hip replacement, with a cemented polished tapered femoral component with a 28 mm diameter and a cobalt-chrome (CoCr) modular head, articulating with a 28 mm CoCr acetabular bearing surface secured in a titanium alloy uncemented shell. Between 1997 and 2004, 545 patients with 652 affected hips underwent replacement using this system. Up to 31 January 2008, 90 (13.8%) hips in 82 patients had been revised. Pain was the sole reason for revision in 44 hips (48.9%) of which 35 had normal plain radiographs. Peri-prosthetic fractures occurred in 17 hips (18.9%) with early dislocation in three (3.3%) and late dislocation in 16 (17.8%). Infection was found in nine hips (10.0%). At operation, a range of changes was noted including cavities containing cloudy fluid under pressure, necrotic soft tissues with avulsed tendons and denuded osteonecrotic upper femora. Corrosion was frequently observed on the retrieved cemented part of the femoral component. Typically, the peri-operative findings confirmed those found on pre-operative metal artefact reduction sequence MRI and histological examination showed severe necrosis. Metal artefact reduction sequence MRI proved to be useful when investigating these patients with pain in the absence of adverse plain radiological features.

Degradome expression profiling in human articular cartilage

IntroductionThe molecular mechanisms underlying cartilage destruction in osteoarthritis are poorly understood. Proteolysis is a key feature in the turnover and degradation of cartilage extracellular matrix where the focus of research has been on the metzincin family of metalloproteinases. However, there is strong evidence to indicate important roles for other catalytic classes of proteases, with both extracellular and intracellular activities. The aim of this study was to profile the expression of the majority of protease genes in all catalytic classes in normal human cartilage and that from patients with osteoarthritis (OA) using a quantitative method.MethodsHuman cartilage was obtained from femoral heads at joint replacement for either osteoarthritis or following fracture to the neck of femur (NOF). Total RNA was purified, and expression of genes assayed using Taqman® low-density array quantitative RT-PCR.ResultsA total of 538 protease genes were profiled, of which 431 were expressed in cartilage. A total of 179 genes were differentially expressed in OA versus NOF cartilage: eight aspartic proteases, 44 cysteine proteases, 76 metalloproteases, 46 serine proteases and five threonine proteases. Wilcoxon ranking as well as the LogitBoost-NR machine learning approach were used to assign significance to each gene, with the most highly ranked genes broadly similar using each method.ConclusionsThis study is the most complete quantitative analysis of protease gene expression in cartilage to date. The data help give direction to future research on the specific function(s) of individual proteases or protease families in cartilage and may help to refine anti-proteolytic strategies in OA.

Continuous compartment pressure monitoring vs. clinical monitoring in tibial diaphyseal fractures

A cohort of 109 consecutive patients with a tibial fracture who underwent continuous compartment pressure monitoring of the anterior compartment of the leg were reviewed and compared to a historical control group of the immediate previous 109 patients who were clinically monitored. Of these patients 33 underwent fasciotomies for acute compartment syndrome in association with tibial diaphyseal fractures. Seventeen patients had continuous compartment pressure monitoring and 16 clinical assessments alone. The fasciotomy rate of patients who underwent continuous compartment pressure monitoring was 15.6%. Patients who were not monitored had a fasciotomy rate of 14.7%. The mean time delay from injury to fasciotomy was 22 h in the monitored group and 23 h in the non-monitored group. Continuous compartment pressure monitoring did not increase the rate of unnecessary fasciotomies. We could not demonstrate a significant difference in terms of clinical outcome and time delay from injury to fasciotomy.

Immediate full-weight-bearing mobilisation for repaired Achilles tendon ruptures: a pilot study

Recent experimental and clinical evidence suggests that early loading and mobilisation for Achilles tendon ruptures may improve functional outcomes. This paper presents the results of a pilot study designed to assess the safety of immediate weight-bearing mobilisation. Twenty-eight operatively repaired patients were randomised to either immediate loading in an orthosis or traditional serial plaster casting. An independent observer, blinded to treatment, assessed the results. Improved clinical, anthropometric, and functional outcomes were noted in the immediate loading group. Ultrasound assessment confirmed no deleterious effects upon the tenodesis. There was one re-rupture of the tendon at a minimum follow-up of 1 year.

Accuracy of clinical diagnosis in patients undergoing knee arthroscopy.

A retrospective analysis of patients who underwent knee arthroscopy was undertaken to determine the accuracy of clinical diagnosis when compared with arthroscopic findings, and to see whether any specific pathologies were difficult to diagnose. The preoperative diagnosis was compared with the operative findings and the accuracy, sensitivity and specificity of the clinical diagnosis calculated. Six hundred ninety-eight patients were included. The overall accuracy, sensitivity and specificity of clinical diagnosis was 99%, 70% and 99%, respectively. Ninety percent of patients underwent a beneficial procedure, while 10% had a normal knee diagnosed at operation. Medial meniscal tear was the hardest pathology to diagnose with accuracy, sensitivity and specificity rates of 82%, 92% and 79%, respectively. Clinical examination remains an accurate method of assessing whether patients would benefit from an arthroscopy, although the correct diagnosis may not be determined preoperatively, particularly if pain was located in the medial tibio-femoral joint.

The optimum knee flexion angle for skyline radiography is thirty degrees.

There is wide variation in practice among orthopaedic surgeons regarding the use of skyline tangential patellar radiographs of the patellofemoral joint in patients with anterior knee pain. Various techniques are available for taking such radiographs and numerous radiologic parameters can be measured from them. There is no information as to which knee flexion angle is superior when taking skyline radiographs. The purpose of the current study was to compare the results of skyline radiographs taken at 30°, 50°, and 90° knee flexion. Sixty-seven knees were studied prospectively. All radiographs were made anonymous and then were studied in random order by two observers. Five recognized patellofemoral parameters were recorded. All the parameters studied were measured most reproducibly when measured from the radiograph taken at 30° knee flexion. The parameters were least reproducible when measured from the radiograph taken at 90° knee flexion. In terms of detecting abnormality of the parameters measured, the radiographs taken at 30° and 50° were similar. The radiograph taken at 90° knee flexion detected the fewest abnormalities. Skyline radiographic examination of the patellofemoral joint should be a mandatory part of the investigation of all knee problems. One radiograph, ideally taken at 30° knee flexion, offers the best means of assessing the patellofemoral joint. There is no benefit to requesting multiple images at different angles of knee flexion.

Does pre-operative psychological distress affect patient satisfaction after primary total hip arthroplasty?

BackgroundThere are concerns that pre-operative psychological distress might be associated with reduced patient satisfaction after total hip replacement (THR).MethodsWe investigated this in a multi-centre prospective study between January 1999 and January 2002. We dichotomised the patients into the mentally distressed (MHS ≤ 56) and the not mentally distressed (MHS > 56) groups based on their pre-operative Mental Health Score (MHS) of SF36.Results448 patients (340 not distressed and 108 distressed) completed the patient satisfaction survey. Patient satisfaction rate at five year was 96.66% (415/448). There was no difference in patient satisfaction or willingness to have the surgery between the two groups. None of pre-operative variables predicted five year patient satisfaction in logistic regression.ConclusionsPatient satisfaction after surgery may not be adversely affected by pre-operative psychological distress.

Early failure of a Birmingham resurfacing hip replacement with lymphoreticular spread of metal debris: pre-operative diagnosis with MR

Metal-on-metal hip replacements are the subject of much current debate. There is some evidence that there may be a hypersensitivity reaction, specific to metal-on-metal total hip replacements (THRs), which is associated with early failure of these prostheses. It has to date only been described in total replacements and not in metal-on-metal hip resurfacing. We present the case of a 68-year-old man who underwent bilateral metal-on-metal hip resurfacing for osteoarthrosis. The patient presented 6 months after surgery with pain and lateral thigh swelling. Pre-operative ultrasound and MRI demonstrated findings similar to those described in early failing metal-on-metal THRs, as well as evidence of lymphoreticular spread of metal debris. The operative findings included extensive aseptic soft-tissue necrosis. Histology revealed necrosis and a dense perivascular lymphocytic infiltrate along with metal debris within sinus histiocytes. The surgical, radiological and histological findings are similar to soft-tissue reactions described in metal-on-metal THRs.