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The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 7 | Pages 965 - 968
1 Jul 2005
Stannard JP Singhania AK Lopez-Ben RR Anderson ER Farris RC Volgas DA McGwin GR Alonso JE

We report the incidence and location of deep-vein thrombosis in 312 patients who had sustained high-energy, skeletal trauma. They were investigated using magnetic resonance venography and Duplex ultrasound.

Despite thromboprophylaxis, 36 (11.5%) developed venous thromboembolic disease with an incidence of 10% in those with non-pelvic trauma and 12.2% in the group with pelvic trauma. Of patients who developed deep-vein thrombosis, 13 of 27 in the pelvic group (48%) and only one of nine in the non-pelvic group (11%) had a definite pelvic deep-vein thrombosis. When compared with magnetic resonance venography, ultrasound had a false-negative rate of 77% in diagnosing pelvic deep-vein thrombosis. Its value in the pelvis was limited, although it was more accurate than magnetic resonance venography in diagnosing clots in the lower limbs. Additional screening may be needed to detect pelvic deep-vein thrombosis in patients with pelvic or acetabular fractures.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 12 | Pages 1660 - 1665
1 Dec 2006
Surendran S Kim SH Jee BK Ahn SH Gopinathan P Han CW

We stably transfected early passage chondrocytes with an anti-apoptotic Bcl-2 gene in vitro using a retrovirus vector. Samples of articular cartilage were obtained from 11 patients with a mean age of 69 years (61 to 75) who were undergoing total knee replacement for osteoarthritis. The Bcl-2-gene-transfected chondrocytes were compared with non-transfected and lac-Z-gene-transfected chondrocytes, both of which were used as controls. All three groups of cultured chondrocytes were incubated with nitric oxide (NO) for ten days. Using the Trypan Blue exclusion assay, an enzyme-linked immunosorbent assay and flow cytometric analysis, we found that the number of apoptotic chondrocytes was significantly higher in the non-transfected and lac-Z-transfected groups than in the Bcl-2-transfected group (p < 0.05). The Bcl-2-transfected chondrocytes were protected from NO-induced impairment of proteoglycan synthesis.

We conclude that NO-induced chondrocyte death involves a mechanism which appears to be subject to regulation by an anti-apoptotic Bcl-2 gene. Therefore, Bcl-2 gene therapy may prove to be of therapeutic value in protecting human articular chondrocytes.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 10 | Pages 1317 - 1323
1 Oct 2007
Kim Y Yoon S Kim J

We compared the results of 146 patients who received an anatomic modular knee fixed-bearing total knee replacement (TKR) in one knee and a low contact stress rotating platform mobile-bearing TKR in the other. There were 138 women and eight men with a mean age of 69.8 years (42 to 80). The mean follow-up was 13.2 years (11.0 to 14.5). The patients were assessed clinically and radiologically using the rating systems of the Hospital for Special Surgery and the Knee Society at three months, six months, one year, and annually thereafter.

The assessment scores of both rating systems pre-operatively and at the final review did not show any statistically significant differences between the two designs of implant. In the anatomic modular knee group, one knee was revised because of aseptic loosening of the tibial component and one because of infection. In addition, three knees were revised because of wear of the polyethylene tibial bearing. In the low contact stress group, two knees were revised because of instability requiring exchange of the polyethylene insert and one because of infection.

The radiological analysis found no statistical difference in the incidence of radiolucent lines at the final review (Student’s t-test, p = 0.08), most of which occurred at tibial zone 1. The Kaplan-Meier survivorship for aseptic loosening of the anatomic modular knee and the low contact stress implants at 14.5 years was 99% and 100%, respectively, with a 95% confidence interval of 94% to 100% for both designs.

We found no evidence of the superiority of one design over the other at long-term follow-up.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 9 | Pages 1252 - 1256
1 Sep 2006
Mayr E Krismer M Ertl M Kessler O Thaler M Nogler M

A complete cement mantle is important for the longevity of a total hip replacement. In the minimally-invasive direct anterior approach used at the Innsbruck University hospital, the femoral component has to be inserted into the femoral canal by an angulated movement. In a cadaver study, the quality and the extent of the cement mantle surrounding 13 Exeter femoral components implanted straight through a standard anterolateral transgluteal approach were compared with those of 13 similar femoral components implanted in an angulated fashion through a direct anterior approach. A third-generation cementing technique was used. The inner and outer contours of the cement mantles was traced from CT scans and the thickness and cross-sectional area determined.

In no case was the cement mantle incomplete. The total mean thickness of the cement mantle was 3.62 mm (95% confidence interval 3.59 to 3.65). The mean thickness in the group using the minimally-invasive approach was 0.16 mm less than that in the anterolateral group. The distribution of the thickness was similar in the two groups. The mean thickness was less on the anteromedial and anterolateral aspect than on the posterior aspect of the femur.

There is no evidence that the angulated introduction of Exeter femoral components in the direct anterior approach in cadavers compromises the quality, extent or thickness of the cement mantle.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 1 | Pages 129 - 133
1 Jan 2006
Lee SY Miwa M Sakai Y Kuroda R Niikura T Kurosaka M

We have investigated whether cells derived from haemarthrosis caused by injury to the anterior cruciate ligament could differentiate into the osteoblast lineage in vitro. Haemarthroses associated with anterior cruciate ligament injuries were aspirated and cultured. After treatment with β-glycerophosphate, ascorbic acid and dexamethasone or 1,25 (OH)2D3, a significant increase in the activity of alkaline phosphatase was observed. Matrix mineralisation was demonstrated after 28 days and mRNA levels in osteoblast-related genes were enhanced.

Our results suggest that the haemarthrosis induced by injury to the anterior cruciate ligament contains osteoprogenitor cells and is a potential alternative source for cell-based treatment in such injury.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 9 | Pages 1165 - 1171
1 Sep 2007
Gohil S Annear PO Breidahl W

Animal studies have shown that implanted anterior cruciate ligament (ACL) grafts initially undergo a process of revascularisation prior to remodelling, ultimately increasing mechanical strength. We investigated whether minimal debridement of the intercondylar notch and the residual stump of the ruptured ACL leads to earlier revascularisation in ACL reconstruction in humans. We undertook a randomised controlled clinical trial in which 49 patients underwent ACL reconstruction using autologous four-strand hamstring tendon grafts. Randomised by the use of sealed envelopes, 25 patients had a conventional clearance of the intercondylar notch and 24 had a minimal debridement method. Three patients were excluded from the study. All patients underwent MR scanning postoperatively at 2, 6 and 12 months, together with clinical assessment using a KT-1000 arthrometer and International Knee Documentation Committee (IKDC) evaluation. All observations were made by investigators blinded to the surgical technique. Signal intensity was measured in 4 mm diameter regions of interest along the ACL graft and the mid-substance of the posterior cruciate ligament.

Our results indicate that minimal debridement leads to earlier revascularisation within the mid-substance of the ACL graft at two months (paired t-test, p = 0.002). There was a significant reduction of mid-substance signal six months after the minimal debridement technique (paired t-test, p = 0.00007). No statistically significant differences were found in tunnel placement, incidence of Cyclops lesions, blood loss, IKDC scores, range of movement or Lachman test between the two groups.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 11 | Pages 1441 - 1447
1 Nov 2006
Cui W Won Y Baek M Kim K Cho J

The appearance of the ‘grand-piano sign’ on the anterior resected surface of the femur has been considered to be a marker for correct femoral rotational alignment during total knee replacement. Our study was undertaken to assess quantitatively the morphological patterns on the resected surface after anterior femoral resection with various angles of external rotation, using a computer-simulation technique. A total of 50 right distal femora with varus osteoarthritis in 50 Korean patients were scanned using computerised tomography. Computer image software was used to simulate the anterior femoral cut, which was applied at an external rotation of 0°, 3° and 6° relative to the posterior condylar axis, and parallel to the surgical and clinical epicondylar axes in each case. The morphological patterns on the resected surface were quantified and classified as the ‘grand-piano sign’, ‘the boot sign’ and the ‘butterfly sign’. The surgeon can use the analogy of these quantified sign patterns to ensure that a correct rotational alignment has been obtained intra-operatively.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 1 | Pages 49 - 53
1 Jan 2006
Tsumara N Yoshiya S Chin T Shiba R Kohso K Doita M

We undertook a prospective, randomised study in order to evaluate the efficacy of clamping the drains after intra-articular injection of saline with 1:500 000 adrenaline compared with post-operative blood salvage in reducing blood loss in 212 total knee arthroplasties. The mean post-operative drained blood volume after drain clamping was 352.1 ml compared to 662.3 ml after blood salvage (p < 0.0001). Allogenic blood transfusion was needed in one patient in the drain group and for three in the blood salvage group. Drain clamping with intra-articular injection of saline with adrenaline is more effective than post-operative autologous blood transfusion in reducing blood loss during total knee arthroplasty.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 1 | Pages 114 - 121
1 Jan 2008
Pendegrass CJ Gordon D Middleton CA Sun SNM Blunn GW

Conventional amputation prostheses rely on the attachment of the socket to the stump, which may lead to soft-tissue complications. Intraosseous transcutaneous amputation prostheses (ITAPs) allow direct loading of the skeleton, but their success is limited by infection resulting from breaching of the skin at the interface with the implant. Keratinocytes provide the skin’s primary barrier function, while hemidesmosomes mediate their attachment to natural ITAP analogues. Keratinocytes must attach directly to the surface of the implant. We have assessed the proliferation, morphology and attachment of keratinocytes to four titaniumalloy surfaces in order to determine the optimal topography in vitro. We used immunolocalisation of adhesion complex components, scanning electron microscopy and transmission electron microscopy to assess cell parameters.

We have shown that the proliferation, morphology and attachment of keratinocytes are affected by the surface topography of the biomaterials used to support their growth. Smoother surfaces improved adhesion. We postulate that a smooth topography at the point of epithelium-ITAP contact could increase attachment in vivo, producing an effective barrier of infection.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 8 | Pages 1157 - 1163
1 Aug 2005
Peter B Zambelli P Guicheux J Pioletti DP

In an attempt to increase the life of cementless prostheses, an hydroxyapatite-coated implant which releases a bisphosphonate has been suggested as a drug-delivery system. Our in vitro study was designed to determine the maximum dose to which osteoblasts could be safely exposed.

Our findings demonstrated that zoledronate did not impair the proliferation of human osteoblasts when used at concentrations below 1 μm. Murine cells can be exposed to concentrations as high as 10 μm.

A concentration of 0.01% of titanium particles did not impair the proliferation of either cell line. Zoledronate affected the alkaline phosphatase activity of murine osteoblasts through a chelation phenomenon. The presence of titanium particles strongly decreased the alkaline phosphatase activity of murine osteoblasts. We did not detect any synergic effect of zoledronate and titanium particles on the behaviour of both human and murine osteoblasts.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 4 | Pages 544 - 553
1 Apr 2006
Akmal M Anand A Anand B Wiseman M Goodship AE Bentley G

Bovine and human articular chondrocytes were seeded in 2% alginate constructs and cultured for up to 19 days in a rotating-wall-vessel (RWV) and under static conditions. Culture within the RWV enhanced DNA levels for bovine chondrocyte-seeded constructs when compared with static conditions but did not produce enhancement for human cells. There was a significant enhancement of glycosaminoglycans and hydroxyproline synthesis for both bovine and human chondrocytes. In all cases, histological analysis revealed enhanced Safranin-O staining in the peripheral regions of the constructs compared with the central region. There was an overall increase in staining intensity after culture within the RWV compared with static conditions. Type-II collagen was produced by both bovine and human chondrocytes in the peripheral and central regions of the constructs and the staining intensity was enhanced by culture within the RWV. A capsule of flattened cells containing type-I collagen developed around the constructs maintained under static conditions when seeded with either bovine or human chondrocytes, but not when cultured within the RWV bioreactor.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 5 | Pages 672 - 685
1 May 2007
Goodrich LR Hidaka C Robbins PD Evans CH Nixon AJ

Gene therapy with insulin-like growth factor-1 (IGF-1) increases matrix production and enhances chondrocyte proliferation and survival in vitro. The purpose of this study was to determine whether arthroscopically-grafted chondrocytes genetically modified by an adenovirus vector encoding equine IGF-1 (AdIGF-1) would have a beneficial effect on cartilage healing in an equine femoropatellar joint model.

A total of 16 horses underwent arthroscopic repair of a single 15 mm cartilage defect in each femoropatellar joint. One joint received 2 × 107 AdIGF-1 modified chondrocytes and the contralateral joint received 2 × 107 naive (unmodified) chondrocytes. Repairs were analysed at four weeks, nine weeks and eight months after surgery. Morphological and histological appearance, IGF-1 and collagen type II gene expression (polymerase chain reaction, in situ hybridisation and immunohistochemistry), collagen type II content (cyanogen bromide and sodium dodecyl sulphate-polyacrylamide gel electrophoresis), proteoglycan content (dimethylmethylene blue assay), and gene expression for collagen type I, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, aggrecanase-1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-3 were evaluated.

Genetic modification of chondrocytes significantly increased IGF-1 mRNA and ligand production in repair tissue for up to nine weeks following transplantation. The gross and histological appearance of IGF-1 modified repair tissue was improved over control defects. Gross filling of defects was significantly improved at four weeks, and a more hyaline-like tissue covered the lesions at eight months. Histological outcome at four and nine weeks post-transplantation revealed greater tissue filling of defects transplanted with genetically modified chondrocytes, whereas repair tissue in control defects was thin and irregular and more fibrous. Collagen type II expression in IGF-1 gene-transduced defects was increased 100-fold at four weeks and correlated with increased collagen type II immunoreaction up to eight months.

Genetic modification of chondrocytes with AdIGF-1 prior to transplantation improved early (four to nine weeks), and to a lesser degree long-term, cartilage healing in the equine model.

The equine model of cartilage healing closely resembles human clinical cartilage repair. The results of this study suggest that cartilage healing can be enhanced through genetic modification of chondrocytes prior to transplantation.