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Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_1 | Pages 7 - 7
1 Jan 2014
Al-Naser S Judd J Clarke NMP
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Femoral head deformity can be a devastating outcome in a small percentage of patients with Perthes' disease. Deformities usually start during the fragmentation stage. In this study, we aimed to determine the effects of Vitamin D deficiency on the natural history of Perthes' disease.

Patients with Perthes' disease and Vitamin D deficiency presenting to our unit in the last 3 years were identified. All X-rays were reviewed retrospectively to determine the duration of the fragmentation and ossification stages. Treatment methods were obtained from the notes. Late presenters (i.e. after fragmentation stage) were excluded.

In our unit, Vitamin D deficiency is diagnosed if levels <72 nmol/L. Fifteen patients (17 hips) with Perthes' disease were found to be Vitamin D deficient. Levels ranged from (18–71 nmol/L). The mean length of the fragmentation stage was 15.7 months which is significantly higher than quoted literature figures (8 months). Ossification stage duration was 18.8 months which was comparable to quoted figures. However, patients with severe Vitamin D deficiency (< 52 nmol/L) were found to have longer ossification stage (20.6 months) compared with patients with mild deficiency (52–72 nmol/L) (16.4 months). Seven out of 16 patients (44%) required surgical containment which is significantly higher than the usually low rates of surgical intervention.

The critical fragmentation stage in Vitamin D deficiency is significantly longer putting the femoral head at higher risk of deformity and extrusion. This leads to higher rates of surgical containment. Also the severity of Vitamin D deficiency might be an important determinant of the period of time required for ossification and healing.

Vitamin D level is an important prognostic factor and must be measured in all patients with Perthes' disease. Prescribing Vitamin D supplements is advisable in this group of patients. However, the effects of these supplements on the course of the disease requires further research.

Level of evidence: III


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 375 - 375
1 Jul 2010
Woodsford MN Narayanan UG Leahy R Janicki J Faust S Clarke NMP
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Introduction: Methicillin-sensitive staphylococcus aureus (MSSA) has been the predominant aetiological agent in acute osteomyelitis (AHO) in children. Recent studies from the United States have demonstrated an increase in community-acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, which have been linked to increased morbidity.

Aim: a) to compare the patterns of AHO including the incidence of CA-MRSA in two tertiary children’s hospitals in Canada (The Hospital for Sick Children) and the United Kingdom (Southampton General Hospital) respectively, b) to compare the clinical course of MSSA versus CA-MRSA AHO in children in these two institutions.

Method: A retrospective review was carried out of all children up to 16 years, who were diagnosed with AHO at both centres over a five-year period. Demographic information, diagnostics, aetiology, treatment and outcomes was collected for comparison across both institutions and between MSSA and CA-MRSA identified patients.

Results: 99 cases of AHO were identified in Toronto (HSC) and 82 cases in Southampton (SGH) over the given time frames. The male: female ratios were 1.5:1 at HSC and 1.7:1 at SGH. The most commonly identified organism at both sites was MSSA, representing 42% of cultures at HSC and 22% at SGH. 2 Cases of CA-MRSA were identified at HSC, while 1 case was identified in Southampton, confirmed to be PVL-positive. No cases of Haemophilus influenzae were identified at either site. There were no significant differences in the median lengths of stay, rates of operative intervention, or complications between the two institutions. CA-MRSA cases were on average younger (7.5 yrs vs 9 yrs) and were all girls, compared with 32% girls in the MSSA group. CA-MRSA patients had similar initial laboratory profiles with the MSSA patients, except for significantly higher C-Reactive Proteins (200 vs 64) (p < 0.05). CA-MRSA patients experienced a significantly longer hospital stay (23 vs 8 days); were more likely to undergo surgical intervention (2/3 vs 34/59); were treated with longer duration of IV antibiotics (34 days vs 10.5 days); and longer total duration of antibiotics (61 days vs 46 days). 1/3 CA-MRSA patients required admission to the ICU for sepsis

Conclusions: MSSA remains the predominant aetiological agent in AHO at two large children’s hospitals in Canada and the UK. The patterns of infection are similar at both sites. CA-MRSA AHO infections have been identified at both centres, and although these remain uncommon, they are associated with a more severe clinical course. One can expect the incidence of CA-MRSA strains to rise, necessitating increased vigilance.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 215 - 215
1 May 2009
Valentine KM Uglow MG Clarke NMP
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Aim: To compare the rate of relapse of Ponseti treatment method with a historical cohort who underwent conventional surgery.

Method and Results: From June 2002 to December 2004, 70 patients presented with 107 clubfeet and started the Ponseti treatment method. 15 feet in 9 patients were excluded due to teratologic deformity. 50 patients with 75 clubfeet were studied (41 boys and 9 girls). There was at least a two-year follow up period, or failure of the Ponseti method within this time frame. Data was compiled from clinic assessment forms and patient notes. All cases resulting in recasting or further surgical procedures were regarded as failure of conservative treatment. This was compared to published data from the same centre, regarding relapse for the two-stage surgical method. From 1988 to 1995, 86 patients presented with 120 clubfeet and had surgical treatment. 68 patients with 91 clubfeet (48 boys 20 girls) had the two-stage surgical procedure and were followed up at a mean age of 5.7 years (2.2 to 9.6). The mean age for surgery was 8.9 months.

Relapse rate of both treatment methods was compared for all feet in all Dimeglio grades. Relapse rates for Ponseti and surgery respectively were: grade 2, 18.2% vs 0%; grade 3, 36.2% vs 20.4%; grade 4, 35.3% vs 65.4%. The differences were not statistically significant

Conclusions: The Ponseti method is as valid as the two-stage surgical method for the treatment of clubfoot. Functional outcomes of the two treatment methods need to be compared.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 404 - 404
1 Oct 2006
Cheung KSC Yamada N Tilley S Clarke NMP Roach HI
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In osteoarthritis (OA) there is a loss of matrix components, especially aggrecan, which is a major structural component important for the integrity and function of articular cartilage. The breakdown of aggrecan is mediated by enzymes from the ADAM-TS (a disintegrin and metalloproteinase with thrombospondin motifs) family and recent studies have suggested that, in humans, ADAM-TS4 (aggrecanase-1) plays a major role. Articular chondrocytes do not express ADAM-TS4 in contrast to clonal OA chondrocytes. Since in any somatic cell non-expressed genes are thought to be silenced by DNA methylation in the promoter region, the aims of the project were twofold:

to localize enzyme expression for ADAM-TS4 by immunocytochemistry and

to determine whether ‘unsilencing’ (i.e. DNA de-methylation) in the promoter of ADAM-TS4 was associated with the abnormal enzyme synthesis.

Using immunocytochemistry, we confirmed that there is an increased expression of ADAM-TS4 in OA chondrocytes, which initially occurs in chondrocytes of the superficial zone. As the Mankin score increases, ADAM-TS4 positive chondrocytes were found in duplets, then quadruplets until, at Mankin score > 10, all the cells in a typical OA clone were immunopositive for ADAM-TS4, suggesting that abnormal enzyme expression was inherited by daughter cells. DNA was extracted from femoral head cartilage of 24 patients, who had undergone hip replacement surgery for either symptomatic OA or following a fracture of neck of femur (#NOF). The latter was used as control due to the inverse relationship between OA and osteoporosis. For OA samples, it was important to sample only those regions for which immunocytochemistry had shown the presence of ADAM-TS4 synthesizing cells, i.e. the superficial zones near the weight-bearing region. DNA methylation only occurs at cytosines of the sequence 5′...CG...3′, the so-called CpG sites. To determine methylation status of specific CpG sites, methylation sensitive restriction enzymes were used, which will only cut DNA in the absence of methylation. By designing PCR primers that bracketed these sites, presence or absence of PCR bands could distinguish between methylated and non-methylated CpGs respectively. The ADAM-TS4 promoter contains a total of 13 CpG sites. Using restriction enzyme/primers combinations, it was possible to analyze 7 of these sites for methylation status. In the control group, all 7 CpG sites were methylated, while there was an overall 49% decrease of methylation in the OA group (p=< 0.0001). Some of the CpG sites were more consistently demethylated then others, one site at −753bp upstream from the transcription start site, showed a 86% decrease in methylation in OA compared to the control group (p=0.0005), while at other sites the decrease in methylation ranged from 36–50%. Conclusions. This study confirmed by immunocytochemistry that ADAM-TS4 is produced by OA chondrocytes, contributing to the degradation of their matrix. This abnormal enzyme expression is associated with DNA methylation. If a causal relationship could be proven in the future, then DNA de-methylation might play an important role in the pathogenesis of osteoarthritis and future therapies might be directed at influencing the methylation status.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 435 - 435
1 Oct 2006
Sakthivel VK Goddard M Sabouni MY Clarke NMP
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Introduction: There is some debate about the pros and cons of selective screening of DDH in neonates as opposed to general screening. General screening puts a lot of stress on the resources available, especially in the modern day NHS, but the advocates state that this minimises the cost incurred in treating a missed DDH (by selective screening) with surgery later on.

Aim: The aim of this retrospective study was to find out the effectiveness of the Southampton selective screening of babies with risk factors for DDH by finding out the number of patients presenting late with an established DDH.

Materials And Methods: 6116 babies out of 26,932 live births (22.7%) in Southampton were screened between 1998 and 2003. The details of the individual outcomes and the reasons for the late presentation were obtained from the patient notes and the records of the screening program which are maintained in the clinics and by the senior author.

Results: 248 new patients had Pavlik’s harness fitted for the treatment of DDH which presents a treatment rate of 0.92%. 8 patients (0.03%) presented late because they did not undergo ultrasound scanning as they did not have the risk factors as required by this selective program. 10 (0.036%) failed Pavlik’s and needed late surgery to have their DDH treated. The total operation rate was 0.066%.

Discussion: The late presentation of patients in this screening program is very low and comparable to the other papers from this department and from around the world. The cost implications of treating these 8 late presenting patients was found to be a lot cheaper than carrying out a general screening program which would mean, in this case 4 times more than the cost of the present screening program.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_I | Pages 70 - 71
1 Mar 2005
Clarke NMP FRCS C
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Introduction: It has been proposed that the presence of the capital femoral ossific nucleus confers protection against ischaemic injury or avascular necrosis (at the time of reduction of a congenitally dislocated hip). The current literature is contradictory.

Materials & Methods: A prospective study was undertaken of the clinical and radiological outcomes following closed or open reduction. 50 hips were included in the study. These cases had either presented late or had failed conservative treatment. In 28 hips treatment was intentionally delayed until the appearance of the ossific nucleus (but not beyond 13 months) and in 22 the ossific nucleus was present at clinical presentation. 6 hips reached the age of 13 months without an ossific nucleus appearing and progressed to treatment. The significant avascular necrosis rate (> grade 1) was 7% for closed reduction and 14% for open. However, the amended rate if hips were excluded that had failed Pavlik harness treatment was 0.0% and 9% respectively (4% overall). Further surgical procedures were necessary in 57% of hips undergoing closed reduction and 41% after open, which compares favourably with other series.

Discussion: It is concluded that the presence of the ossific nucleus is an important factor in the prevention of AVN, particularly after late closed reduction. Intentional delay in the timing of surgery does not condemn a hip to open surgery but there is a comparable rate of secondary procedures becoming necessary particularly after closed reduction. The delayed strategy to await the appearance of the ossific nucleus for previously untreated dislocation allows a simple treatment algorithm to be employed which produces good clinical and radiological outcomes. The use of the Pavlik harness has been abandoned in cases of irreducible dislocation of the hip.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_II | Pages 196 - 196
1 Feb 2004
Antapur P Gent E Clarke NMP Taylor GR
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Aim: Unicameral bone cysts are difficult to treat as partial cyst healing may reverse and it may be difficult to assess between active and latent types.

Materials and Methods: 19 patients with unicameral bone cysts were reviewed with a mean age of 8.5 years (16 males and 3 females). These 19 patients were reviewed over a period of fifteen years and all except one, had an active cyst abutting the growth plate. 18 cases were treated with curettage and burring using a dental burr and six cases were treated with elastic nailing. 12 cases were treated with bone marrow injection either alone or in combination with the above procedures. 2 cases were treated with steroid injections. No cases were bone grafted.

Results: The best results were obtained with curettage and burring of the lining of the cysts. Bone marrow injection alone did not produce resolution of any of the cysts. Migration of the cysts away from the growth plate in response to treatment (conversion from active to latent status) was predictive of successful treatment with no symptoms and no further fractures, irrespective of the age of the patient.

Conclusion: Successful treatment of unicameral bone cysts can be predicted by the appearance of normal bone formation by the physis and subsequent migration of the cyst away from the growth plate. The association of successful treatment and conversion to latency of the cyst has not previously been reported.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_II | Pages 97 - 97
1 Feb 2003
Cashman JP Round J Taylor G Clarke NMP
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Between June 1988 and December 1997, 332 babies with 546 dysplastic hips were treated in the Pavlik harness for primary Developmental Dysplasia (DDH) as a product of the Southampton selective screening program. Each was managed by a strict protocol including ultrasonic monitoring of treatment within the harness. The group was prospectively studied over a mean duration of 6. 5 years (SD=2. 7y) with 89. 1% follow-up. The Acetabular Index (AI) and Centre-Edge angle of Wiberg (CEA) were measured on annual radiographs to determine the natural history of hip development following treatment in the Pavilik harness. These were compared to published normal values.

We observed a failed reduction rate of 15. 2% of all complete hip dislocations; these required alternative surgical treatment. The development of those hips of infants successfully treated in the harness showed no significant difference from the normal values of Acetabular Index for female left hips, after eighteen months of age. Of those dysplastic hips that were successfully reduced in the harness; 2. 4% exhibited persisting significant late dysplasia (CEA< 20°) and 0.2% demonstrated persistent severe late dysplasia (CEA< 15 °) All such cases could be identified at sixty months. Dysplasia was clinically deemed sufficient to merit innominate osteotomy in 0. 9% dysplastic hips treated. Avascular necrosis was noted in 1% of hips treated in the harness.

We conclude that using our protocol, successful initial treatment of DDH with the Pavlik harness appears to revert the natural history of hip development to that of the normal population. We recommend that regular radiographic surveillance up to 60 months of age constitutes safe and effective practice.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_II | Pages 150 - 150
1 Jul 2002
Mehta G Oreffo RO Langley-Evans SC Cooper C Clarke NMP Roach HI
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Cohort studies in humans have suggested that the peak bone mass attained at skeletal maturity may be programmed in utero. To investigate which aspects of bone development might be influenced in utero, we utilised a rat model of maternal protein insufficiency, which has previously been used to demonstrate the fetal origin of adult hypertension. In rodents, a growth plate remains present throughout life, even after longitudinal growth ceases. Generally, the height of the growth plate is related to the rate of bone growth. Fast growing bones have maximal height growth plates, and as bone growth slows down the height decreases until it remains stationary.

The aim of this study was to compare the morphology of long bones in aged rats that had been subjected to protein insufficiency in utero with that of controls. Rat dams were fed either an 18% casein control diet or a 9% casein low protein diet from conception until the end of pregnancy. The offspring were fed a normal diet until death (~72 weeks), when bone density was measured by dual energy X-ray absorptiometry (DEXA) and the tibiae and femurs were processed for histology.

The offspring of rats from the low protein group had a significantly lower bone mass, as assessed by DEXA. The major differences in bone structure were found in the growth plates, which were very irregular without the usual zones of resting, proliferating and hypertrophic chondrocytes. A number of unusual cellular events were noted to have taken place subsequent to cessation of growth, including: a) elimination of all chondrocytes in a number of regions, resulting in vast acellular areas; b) formation of chondroid bone and/or transdifferentiation of chondrocytes to bone-forming cells in other regions; c) partial resorption of those latter regions while the acellular regions were not resorbed; d) ‘horizontal’ apposition of bone against a smooth metaphyseal edge of the growth plate.

To compare the growth plates from the low and high protein groups semi-quantitatively, the degrees of the above features were scored. In addition, the heights of the growth plates were were assessed by two independent measurements. In the low protein group, the height of the growth plate were found to be significantly greater (p< 0.001). Additionally, the growth plates from this group of animals were observed to be more irregular with regards to all the features outlined above.

These findings are consistent with the hypothesis that growth trajectory and bone mass are programmed in early life. The increased height of the growth plate in animals undernourished in utero may reflect the cessation of growth at an earlier age. The increased irregularity of the growth plate in this group of animals may infer an earlier onset of age-related changes within the growth cartilage.