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Biomedical subjects

Simon T Donell

Publications and source records attributed to Simon T Donell.

13 recordsLinked to original sources
PubMed2007

Isolated patellofemoral osteoarthritis.

Isolated patellofemoral osteoarthritis is now recognised to be more common than previously thought. The features and management are reviewed, including the various surgical options in symptomatic patients. The evidence base for managing patellofemoral osteoarthritis is behind that for the tibiofemoral joint. All treatments are based on uncontrolled observational case series, typically retrospectively reviewed. Fortunately the majority of patients with isolated patellofemoral degenerative changes do not need surgical treatment. Those who are symptomatic can usually be successfully treated with weight loss and quadriceps strengthening exercises.

Arthroplasty, Replacement, Knee↗
PubMed2006

Modified Dejour trochleoplasty for severe dysplasia: operative technique and early clinical results.

Instability of the patella occurs when it fails to track fully in the femoral groove during knee movement. The groove begins at the metaphysis of the distal femur and extends on its anterior surface inferiorly to the femoral notch. It is normally present at birth and the cartilaginous shape is similar to that of the adult. An abnormal trochlea may be shallow. In extreme cases it may be dome-shaped, where it is associated with recurrent subluxation or dislocation of the patella. In these cases it is logical to consider fashioning a groove as part of a realignment procedure. This study reports the operative technique and early clinical and radiological results of a consecutive case series of the first 15 patients (17 knees) who underwent a deepening trochleoplasty for severe dysplasia developed from that described by Dejour. The follow-up was for a minimum of 1 year (average 3 years, range 1 to 9 years). The boss height was reduced from an average of 7.5 mm (range 6 to 11 mm) to 0.7 mm (range -1 to 3 mm). Tracking became normal in 11 knees and had a slight J-shaped in six. Seven knees had mild residual apprehension. Seven patients were very satisfied, six were satisfied, and two were disappointed. The Kujala score improved from an average of 48 (range 13 to 75) to 75 (range 51 to 98) out of 100 (p<0.05). Three patients returned to full sports. Eight patients required further operations apart from the removal of metallic screws in 10 knees. Five of these were arthroscopic arthrolysis for stiffness at about 6 weeks post-operatively. Trochleoplasty for severe dysplasia of the femoral sulcus is a developing procedure. It requires careful attention to detail. For a rare condition the early results have been satisfactory with an acceptable level of complications.

Adolescent↗
PubMed2006

Cruciate ligament assessment in MRI scans: a pilot study of a static drawer technique.

Ten subjects with cruciate ligament rupture (five ACL and five PCL), and four normal subjects underwent magnetic resonance imaging (MRI) with a novel splint that stresses the knee. The splint acted as a fulcrum to translate the tibia in an anterior and posterior direction, depending on application. The MRI images showed that translation of the tibial plateaux occurred but not in a simple manner. The resultant images did not show marked anterior tibial translation in the ACL ruptured knee with an anterior drawer, nor posterior tibial translation for the PCL injured knee in posterior drawer. The medial plateau tended to move posteriorly in anterior drawer in the normal knees. The secondary MRI findings of ACL injury and associated meniscal injuries were enhanced. A further study with 50 subjects in each group, and arthroscopic confirmation of the findings, would be required to confirm these results.

Adult↗
PubMed2006

Fibroblast activation protein alpha is expressed by chondrocytes following a pro-inflammatory stimulus and is elevated in osteoarthritis.

Arthritis is characterised by the proteolytic degradation of articular cartilage leading to a loss of joint function. Articular cartilage is composed of an extracellular matrix of proteoglycans and collagens. We have previously shown that serine proteinases are involved in the activation cascades leading to cartilage collagen degradation. The aim of this study was to use an active-site probe, biotinylated fluorophosphonate, to identify active serine proteinases present on the chondrocyte membrane after stimulation with the pro-inflammatory cytokines IL-1 and oncostatin M (OSM), agents that promote cartilage resorption. Fibroblast activation protein alpha (FAPalpha), a type II integral membrane serine proteinase, was identified on chondrocyte membranes stimulated with IL-1 and OSM. Real-time PCR analysis shows that FAPalpha gene expression is up-regulated by this cytokine combination in both isolated chondrocytes and cartilage explant cultures and is significantly higher in cartilage from OA patients compared to phenotypically normal articular cartilage. Immunohistochemistry analysis shows FAPalpha expression on chondrocytes in the superficial zone of OA cartilage tissues. This is the first report demonstrating the expression of active FAPalpha on the chondrocyte membrane and elevated levels in cartilage from OA patients. Its cell surface location and expression profile suggest that it may have an important pathological role in the cartilage turnover prevalent in arthritic diseases.

Animals↗
PubMed2006

A laterally positioned concave trochlear groove prevents patellar dislocation.

Patellofemoral instability is a disabling condition that occurs in adolescence. Recurrence after patellar dislocation has been reported in 2-50% of patients. We compared the distal femur in patients with patellofemoral instability with distal femura of a healthy cohort using mathematical quantification of two-dimensional shape variation at the same position in different knees. One hundred eight computed tomography scans from 54 patients with patellofemoral instability were compared with 197 computed tomography scans from 102 subjects with normal knees. We used principal components analysis to quantify variation in shape of the trochlear groove as it allows comparison of knees with patellofemoral instability to healthy knees. We found that subjects who had dislocated their patella had a flattened trochlear groove, whereas normal knees had a more concave groove. The position of the trochlear groove was more medial in patients with patellofemoral instability compared with normal knees. Groove position was more important than shape when predicting which patellae were likely to dislocate.

Adolescent↗
PubMed2006

The effect of achilles tendon lengthening on ankle dorsiflexion: a cadaver study.

BACKGROUND: Tendon lengthening is an important cause of morbidity after Achilles tendon rupture. However, direct measurement of the tendon length is difficult. Ankle dorsiflexion has, therefore, been used as a surrogate measure on the assumption that it is the Achilles tendon that limits this movement. The aim of this investigation was to assess the relationship between Achilles tendon length and ankle dorsiflexion. The primary question was whether or not the Achilles tendon is the structure that limits ankle dorsiflexion. The secondary purpose was to quantify the relationship between Achilles tendon lengthening and dorsiflexion at the ankle joint. METHODS: Five cadaver specimens were dissected to expose the tendons and capsular tissue of the leg and hindfoot. Fixed bony reference points were used as markers for the measurements. In the first specimen, the Achilles tendon was intact and the other structures that may limit ankle dorsiflexion were sequentially divided. In the other specimens the Achilles tendon was lengthened by 1 cm intervals and the effect upon ankle dorsiflexion movement was recorded. RESULTS: Division of the other tendons and the capsular tissue around the ankle joint did not affect the range of ankle dorsiflexion. When the Achilles was divided the foot could be dorsiflexed until the talar neck impinged upon the anterior aspect of the distal tibia. There was a mean increase of 12 degrees of dorsiflexion for each centimeter increase in tendon length. CONCLUSION: The Achilles tendon is the anatomical structure that limits ankle dorsiflexion, even when the tendon is lengthened. There was a linear relationship between the length of the Achilles tendon and the range of ankle dorsiflexion in this cadaver model. Ankle dorsiflexion would appear to be a clinically useful indicator of tendon length.

Achilles Tendon↗
PubMed2006

The long-term outcome of tendon lengthening for chronic Achilles tendon pain.

BACKGROUND: The purpose of this study was to assess the long-term results of tendon lengthening surgery for the treatment of chronic Achilles tendon pain. METHODS: The results of 21 procedures in 18 patients were assessed. Each patient had an open Z-plasty to lengthen the Achilles tendon by 1 cm. RESULTS: Results showed a long-term (7.5 years) reduction in visual analogue pain scores for sporting activity in 20 of 21 procedures (median 50 point reduction, p < 0.0005). The tendon lengthening was apparent in a mean increase in dorsiflexion of 5 degrees. Two patients had minor gait abnormalities postoperatively. One patient had a reduction in plantarflexion power on the operated side, but five patients had improved power compared to the nonoperated limb. One major and five minor surgical complications were noted. CONCLUSIONS: The retrospective nature of this study must be noted in drawing conclusions. However, the results suggest excellent long-term reduction of Achilles pain after tendon lengthening. This must be weighed against a relatively high complication rate for any procedure in this region. This treatment does not appear to cause long-term deficits in plantarflexion power or gait.

Achilles Tendon↗
PubMed2006

Expression profiling of metalloproteinases and their inhibitors in synovium and cartilage.

Cartilage destruction in osteoarthritis (OA) is thought to be mediated by two main enzyme families; the matrix metalloproteinases (MMPs) are responsible for cartilage collagen breakdown, whereas enzymes from the 'a disintegrin and metalloproteinase domain with thrombospondin motifs' (ADAMTS) family mediate cartilage aggrecan loss. Tissue inhibitors of metalloproteinases (TIMPs) regulate the activity of these enzymes. Although cartilage destruction in OA might be driven by the chondrocyte, low-grade synovitis is reported in patients with all grades of this disease. Our earlier work profiling these gene families in cartilage identified a number of genes that are regulated in OA, which are hence implicated in the disease process. Because the synovium might contribute to cartilage-matrix destruction in OA, we have extended the screening in the current study. We have profiled MMP, ADAMTS and TIMP genes in both cartilage and synovium from patients with either OA of the hip or a fracture to the neck of femur (NOF), giving a more complete picture of proteolysis in this disease. The four most significantly upregulated genes (P < 0.0001) in OA synovium compared to the fractured NOF are MMP28, ADAMTS16, ADAMTS17 and TIMP2. For MMP9, MMP10, MMP12, MMP17, MMP23, MMP28, ADAMTS4, and ADAMTS9, there is a significant correlation between expression levels in the synovium and cartilage, suggesting similar mechanisms of regulation. Additionally, we have shown that in cartilage the median level of steady-state mRNA for MMP13 is approximately 20-fold higher than MMP28 and approximately 1,500-fold higher than ADAMTS16, with expression of this latter gene approximately 150-fold higher in synovium than cartilage. This study is the most comprehensive analysis of the metzincin family of proteinases in the joint to date and has identified several proteinase genes not previously reported to be expressed or regulated in synovium.

ADAM Proteins↗
PubMed2005

Imaging the post-operative meniscus.

Considerable developments have occurred in meniscal surgery, and consequently in the imaging of post-operative menisci, over the last 15 years. A drive to preserve meniscal physiologic function for as long as possible, in order to delay osteoarthrosis, has resulted in limited partial meniscectomies, meniscal repairs and meniscal transplants. Each of these techniques affects the imaging appearance of the meniscus, reducing the accuracy of conventional MRI in predicting recurrent tears. The specificity of conventional MRI can be improved by employing at least two T2-weighted sequences, but this still leaves a shortfall in sensitivity. In an attempt to increase the diagnostic accuracy of cross-sectional imaging, MR arthrography (MRA) and CT arthrography (CTA), have been applied to the post-operative meniscus. Sensitivities and specificities for these two techniques approach 90% in predicting recurrent meniscal tears. In the setting of clinical symptoms and gross meniscal deficiency, meniscal allografts are being transplanted with increasing frequency. In these transplants meniscal degeneration, fragmentation and separation are common findings, but the role of imaging in the management of these patients has not yet been well defined. This review explores the imaging techniques available for the evaluation of the post-operative meniscus, their strengths and weaknesses, and the reasons that they may find a place in a rational strategy for imaging of the symptomatic post-operative knee.

Arthrography↗
PubMed2004

Expression profiling of metalloproteinases and their inhibitors in cartilage.

OBJECTIVE: To profile the expression of all known members of the matrix metalloproteinase (MMP), ADAMTS, and tissue inhibitor of metalloproteinases (TIMP) gene families in normal cartilage and cartilage from patients with osteoarthritis (OA). METHODS: Human cartilage was obtained from femoral heads at joint replacement for OA or following fracture to the femoral neck. Total RNA was purified, and gene expression was assayed using quantitative real-time polymerase chain reaction. RESULTS: Several members of the above gene families were regulated in OA. Genes that showed increased expression in OA were MMP13, MMP28, and ADAMTS16 (all at P < 0.001), MMP9, MMP16, ADAMTS2, and ADAMTS14 (all at P < 0.01), and MMP2, TIMP3, and ADAMTS12 (all at P < 0.05). Genes with decreased expression in OA were MMP1, MMP3, and ADAMTS1 (all at P < 0.001), MMP10, TIMP1, and ADAMTS9 (all at P < 0.01), and TIMP4, ADAMTS5, and ADAMTS15 (all at P < 0.05). Correlation analysis revealed that groups of genes across the gene families were coexpressed in cartilage. CONCLUSION: This is the first comprehensive expression profile of all known MMP, ADAMTS, and TIMP genes in cartilage. Elucidation of patterns of expression provides a foundation with which to understand mechanisms of gene regulation in OA and potentially to refine the specificity of antiproteolytic therapies.

ADAM Proteins↗
PubMed2003

Reliability of isokinetic dynamometry in assessing plantarflexion torque following Achilles tendon rupture.

BACKGROUND: Research investigating the most effective management of Achilles tendon injury has been limited by a lack of reliable outcome measurements. Calf strength may be a valid outcome measure, not only in terms of identifying possible risk factors for reoccurrence of rupture, but also as an indicator of recovery. Isokinetic dynamometry has been suggested as an effective tool for measuring the torque of the calf muscles. Such measurements have demonstrated high reliability for the assessment of calf muscle torque in healthy subjects. However, there are no published data to demonstrate the reliability of isokinetic dynamometry in subjects with pathology in the Achilles tendon. The purpose of this study was to assess the inter- and intraobserver reliability of isokinetic dynamometry for assessing plantarflexion torque following Achilles tendon rupture. METHODS: Two independent observers used the Kin-com Dynamometer to measure the torque of the plantarflexors in 22 subjects 6 months after unilateral rupture of the Achilles tendon. Twelve subjects had been managed operatively and 10 nonoperatively. Subjects were placed in the prone position with the knee extended. Measurements of peak torque, average torque, and total work were made for both concentric and eccentric plantarflexion movements at 60 degrees per second. RESULTS: Intraclass correlation coefficients were used to calculate reliability of measurements both within and between observers. Reliability was slightly greater on the healthy side (0.74-0.92 ICC) in comparison with the injured side (0.74-0.89 ICC). CONCLUSION: The results of this study suggest that isokinetic dynamometry provides a reliable method of measuring the torque of the plantarflexors following rupture of the Achilles tendon, with levels of reliability comparable with those from healthy subjects. The study concludes that this would be a valuable and reliable outcome measure for use in clinical trials.

Achilles Tendon↗
PubMed2002

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. Articular cartilage was obtained from OA patients undergoing arthroplasty, with 'normal' cartilage from trauma surgery for hip fracture. Senescent cells were identified using the senescence-associated beta-galactosidase (SA-beta-gal) marker. Telomere length was assessed using Southern blot. MMP expression was measured at the mRNA level using Taqman RT-PCR. No SA-beta-gal staining was observed in control cartilage regardless of patient age. In contrast, SA-beta-gal staining was observed in damaged OA cartilage adjacent to the lesion. Cultured chondrocytes isolated from sites near a lesion contained a greater percentage of SA-beta-gal positive cells than cultures isolated from distal sites or normal cartilage. Mean telomere length was shorter in cells near the lesion compared to distal sites in the same joint; thus the former population has undergone cell division. The expression of collagenases MMP-1, -8 and -13 and tissue inhibitor of metalloproteinases (TIMP)-1 was altered in OA cartilage, but no difference was detected between lesion and distal sites in the same joint (i.e. no correlation was found between senescent cells and proteinase/ inhibitor expression).

Aged↗