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Papers by Pramod Achan
Intramedullary Fixation of Forearm Fractures Comparison of Elastic Nails or K-Wires
Orthopaedic Proceedings, Mar 1, 2003
Staged management of high-energy proximal tibia fractures
PubMed, 2004
High-energy proximal tibia fractures are complicated by soft tissue compromise and this may resul... more High-energy proximal tibia fractures are complicated by soft tissue compromise and this may result in sub-optimal outcomes. There is a high association of open injuries, compartment syndromes, and vascular injuries with these bony disruptions. Surgical treatment of these injuries has been associated with significant complications such as infection, knee stiffness, malunion, loss of fixation, soft tissue failure, and amputations. The loss of fixation is an issue especially in the elderly, with failure associated with age more than sixty years, premature weight bearing, preoperative displacement, fracture fragmentation, and severe osteoporosis. The use of two-stage reconstruction for the treatment of distal tibia fractures has been successful in decreasing the complication rates, including wound compromise. The two stages involve: 1. stabilization of the injured limb with a bridging external fixator to allow the soft tissues to improve and recover and 2. definitive fixation for reconstruction of the articular surface and meta-diaphyseal fractures. The use of such a protocol has been proposed for high-energy proximal tibia fractures to decrease the high rate of soft tissue compromise associated with traditional open methods of treatment. The choice of definitive fixation may include plates, nails, or non-bridging external fixation.
Comparison of Outcomes and Complications of Hip Arthroscopy for Mixed Hip Disorders Between Adolescents and Adults: A Prospective Cohort Study
Orthopaedic Proceedings, Feb 21, 2018
Aim The current literature indicates that hip arthroscopy is safe in both adolescents and adults ... more Aim The current literature indicates that hip arthroscopy is safe in both adolescents and adults with good early outcomes but there are no available studies that directly compare the outcomes of this procedure for mixed indications between these two groups. Method This was a prospective cohort study of 102 consecutive supine hip arthroscopies in 96 patients (48 adolescent ( 18 hips), mean age 33.8 years) at a tertiary referral paediatric and adult university hospital followed-up for a minimum of two years. Patient demographics, indications for surgery, Modified Harris Hip (MHHS) and Non-Arthritic Hip (NAHS) scores, operative interventions and complications were recorded. Results At two-year follow-up, the MHHS improved from a mean of 55.3 to 87.5 (p Conclusion This study confirms that hip arthroscopy for mixed indications leads to good early outcomes with low complication rates in adolescent and adult patients. The incidence of pudendal nerve palsy in the adolescent group is however noted and is of concern.
Archives of Orthopaedic and Trauma Surgery, Mar 4, 2020
Purpose A potential method to relieve the pain from medial osteoarthritis of the knee is to offlo... more Purpose A potential method to relieve the pain from medial osteoarthritis of the knee is to offload the medial compartment. The Latella ™ Knee Implant is a novel device designed to offload the medial compartment. The objective of the Cotera-1 study was to evaluate the preliminary safety and feasibility of the Latella implant to treat patients with medial OA of the knee, by a 2-year follow-up of a prospective multicenter feasibility study (Cotera-1) performed in the Netherlands and UK Methods In this first-in-man study, 11 participants received the Latella implant and were followed for 2 years, documenting physician assessment, Patient-Reported Outcome (PRO) scoring (KOOS, IKDC, Kujala, SF-36); Patient Global Assessment (PGA), radiographic analysis and MRI analysis, complications, reoperation rate and hip-knee-ankle axis. Results The Latella Knee Implant system proved to be well tolerated and demonstrated a low-risk safety profile up to 24 months post-treatment. A responder analysis was performed of the subjects who still had the Latella implanted at 24-month time point (n = 9). Based on a MCID of eight for KOOS pain sub-scale, 78% of the subjects at the 24 month time point would be considered as responders. Similarly, based on improvement in the medial knee pain compared to baseline using the NRS scale of 1-10, 89% of the subjects at the 24-month time point would be considered as responders. Two patients were revised during follow-up: one for arthrofibrosis and one converted to TKA for progression of OA. Conclusions The early clinical experience with the Latella Knee Implant in this pilot feasibility study has been encouraging. It appears to be a safe implant with possible effect on medial OA. Additional studies need to be performed to assess the safety and efficacy of the procedure in a larger patient population.
Injury-international Journal of The Care of The Injured, May 1, 2003
Intramedullary fixation of children's diaphyseal forearm fractures is becoming the surgical techn... more Intramedullary fixation of children's diaphyseal forearm fractures is becoming the surgical technique of choice, in those cases that warrant surgical intervention. This method offers both technical advantages and patient benefits over alternative techniques and implants that have been used in the past. We present a two-centre study assessing the outcome of either Kirschner wires or elastic stable intramedullary nails (ESIN) as the method of fracture stabilisation in such diaphyseal forearm fractures. A total of 36 children underwent K-wire fixation and 24 children underwent ESIN fixation. All fractures united with no resultant subjective disability. The complication rate following K-wires was 16% and that following nail fixation 9%. Loss of forearm rotation was documented in four children in the K-wire group and three children stabilised with nails. These results confirm an excellent outcome following intramedullary fixation. We have demonstrated no difference in outcome between K-wires and ESIN, although the nails do offer some theoretical advantages.
![Fig. 1. Post-operative radiograph following diaphyseal fracture stabilisation with: (a) K-wires and (b) ESIN A standard surgical technique was performed in both study groups [9,10]. In the majority of cases the radius was stabilised first. This was performed in a retrograde fash- ion via an entry point proximal to the distal physis, in the mid-lateral plane. The ulna wire/nail was inserted antegrade via an entry point distal to the olecranon physis, on the ra- The ESIN were buried under the skin. Initially the fore- arms were splinted with a below elbow cast for up to](https://figures.academia-assets.com/111230179/figure_001.jpg)
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The journal of bone and joint surgery, Apr 1, 2012
THU0023 A novel role for ELR+ CXC chemokine signaling in cartilage homeostasis
Annals of the Rheumatic Diseases, Jun 1, 2013
Background ELR+ CXC chemokine production is studied in arthritis and is thought to contribute to ... more Background ELR+ CXC chemokine production is studied in arthritis and is thought to contribute to inflammation leading to articular cartilage breakdown and arthritis pathology. However, healthy articular chondrocytes express their own chemokine receptors and ligands. The function of CXC chemokine receptors in these cells is puzzling as chondrocytes are encased in a dense extracellular matrix and are not known to migrate in vivo. Objectives This study aims to investigate the function of the CXCR1/2 signaling pathway in articular cartilage. Methods CXCR1/2 expression in adult human articular chondrocytes was confirmed by semi-quantitative RT polymerase chain reaction (RT-PCR), Western blot and immunohistochemistry. Combined and individual functionality of CXCR1 and CXCR2 was tested using an in vitro calcium mobilisation assay. Validated blocking antibodies and siRNA were used to inhibit CXCR1/2 signaling at receptor level. Pertussis toxin, PI3K inhibitors and intracellular calcium chelators were used to block signaling at intracellular levels. The highly sulphated proteoglycan content of chondrocyte micromasses was analysed using Alcian blue staining and spectrophotometric quantification. Chondrocyte gene expression was assessed using real time RT-PCR. CXCL6 and CXCL8 were detected in heparitinase digested, chondroitinase ABC digested and undigested paraffin sections of human articular cartilage from healthy and osteoarthritic donors by immunohistochemistry. Finally, 8 week old CXCR2-/- mutant BALB/C mouse knee joint paraffin sections were analysed using Safranin Orange staining, Chambers scoring and ImageJ histomorphometry. Results CXCR1/2 expression was confirmed in normal human articular cartilage. Individual blockade of either CXCR1 or CXCR2 did not inhibit downstream calcium mobilisation, indicating that CXCR1 and CXCR2 have more functional redundancy than that observed in neutrophils. CXCR1/2 signaling disruption at receptor level or by downstream blockade in chondrocytes resulted in reduced extracellular matrix sulphated glycosaminoglycan content and reduced expression of the chondrocyte differentiation markers COL2A1, Aggrecan, and SOX9. CXCL6 and CXCL8 were found in cartilage extracellular matrix in healthy tissue in distinct localisation patterns, which were disrupted in osteoarthritic tissue and following heparitinase digestion. In vivo analysis of 15 knockout and 15 wild type knees revealed that CXCR2-/- mice have significantly thinner epiphyseal growth plates and medial tibial plateaus, with a reduced sulphated proteoglycan content found in medial condyle articular cartilage. Conclusions Our findings indicate that CXCR1/2 signaling is in fact required for maintenance of phenotypic stability in articular chondrocytes. Interactions with heparan sulphate proteoglycans and distribution patterns of ligands within the ECM, and their disruption during pathology, indicate the presence of a homeostatic mechanism whereby CXC chemokines are retained within the articular cartilage matrix via interactions with heparan sulphate proteoglycans, where they maintain chondrocyte phenotypic stability via an autocrine/paracrine signaling mechanism. In vivo analysis suggests that CXCR1/2 signaling may be specifically required during periods of high chondrocyte turnover, including within the growth plate. Disclosure of Interest None Declared
Interlocked Nailing of the Femur with the Brooker–Wills Nail: Our Experience
Orthopaedic Proceedings, Mar 1, 2009
Intramedullary Nailing is now accepted as the standard treatment for most femoral diaphyseal frac... more Intramedullary Nailing is now accepted as the standard treatment for most femoral diaphyseal fractures. Most intramedullary nails are designed for proximal and distal locking with screws. We describe our experience with the Brooker Wills femoral nail. This nail is unique as distal fixation is achieved with as transverse fixator deployed through slots in the nail, a concept first enunciated by deCamargo in 1952. The fins of the fixator pierce the distal cortex when deployed thereby conferring rotational stability. The entire nail (including the proximal and distal fixation devices) can be inserted through a single proximal incision in the skin. We treated 17 patients with femoral shaft fractures using this system. 93% of the patients were males. Motor vehicle accidents accounted for 80 % of the fractures. Most fractures involved the middle third of the femur (54%), followed by distal third (33%) and proximal third (13%). 67 % of the fractures showed Winquist and Hansen Grade 3 or 4 comminution. All the nailings were performed in the supine position. Static locking was done in 16 cases. Post operative weight bearing was individualized with 86% of the patients bearing full weight before the end of 16 weeks. The average time to full weight bearing was 14 weeks. The mean time to union was 17.1 weeks, with proximal, middle and distal third fractures showing average healing times of 19, 15.6 and 18.8 weeks respectively. All the fractures united. There was one case of delayed union. Intra-operative complications included–inability to deploy the distal fixator in one case and unwinding of the reamer in another case. There was one case of superficial infection where a patient developed a sinus over the metallic fin of the distal fixation device, which had penetrated the cortex. This healed after the distal fixation device was removed. There was one case of proximal nail migration, but the fracture went onto union with some limb shortening. Results were evaluated using the scoring system devised by Sanders etal (1991). The functional criteria in their scoring system include- knee flexion, presence of pain, femur deformity, walking distance, stair climbing and pre injury functional status. We achieved excellent results in 53% of patients, good- 27%, fair–13 % and poor-7%. We feel that the main advantage of the Brooker Wills Nail is the ease of distal locking. This saves time and also leads to lower level of radiation exposure, as the image intensifier is sparingly used for distal locking. In fact, this nail is an attractive option in centres which lack an image intensifier. We achieved good results with this nailing system and feel that it is an acceptable alternative to other nailing systems with conventional locking systems with screws.
Annals of the Rheumatic Diseases, Feb 25, 2013
EWRR abstracts were detectable in connective tissue fibroblasts. In ossified osteophytes (grade 2... more EWRR abstracts were detectable in connective tissue fibroblasts. In ossified osteophytes (grade 2-5), resistin and visfatin and to a lower extend adiponectin were expressed by osteoblasts and resistin and visfatin by osteoclasts. In all osteophyte grades adiponectin was detectable in blood vessels and visfatin was found in about 50% of the chondrocytes. Osteoblast stimulation with adiponectin increased the release of the inflammatory mediators IL-6 (2.6-fold), IL-8 (4.9-fold), and MCP-1 (2.1-fold). In contrast, resistin led to a non-significant decrease of these factors. The osteoblast populations showed individual differences in the baseline expression of the analysed factors and in their responsiveness to adipocytokines. Conclusions The adiponectin and visfatin expression in osteophyte connective tissue and cartilage suggests their involvement in early osteophyte development. Resistin and visfatin in osteoblasts and osteoclasts in ossified osteophytes indicates a role in osteophyte formation at later stages. The stimulation of osteoblasts with adiponectin induces the release of inflammatory mediators. Therefore, the analysed adipocytokines most likely are involved in osteophyte formation at different stages and correspondingly affect cells of cartilage and bone formation to a different extent.
Osteoarthritis and Cartilage, Sep 1, 2008
Clavicular Hook Plate: Not an Ideal Implant
Orthopaedic Proceedings, Mar 1, 2009
The aim of our study was to assess the use of the Clavicular Hook Plate in treating acromio–clavi... more The aim of our study was to assess the use of the Clavicular Hook Plate in treating acromio–clavicular joint dislocations and fractures of the distal clavicle. The prospective study was carried out at two hospitals- a teaching hospital and a district general hospital. Between 2001 and 2004 a total of 37 patients with AC joint injuries and distal clavicle fractures were treated surgically with this device. Four of the patients had sustained a Neers Type 2 fracture of the distal clavicle, while 33 patients had acromio-clavicular joint dislocation (Rockwood Type 3 or higher). Mean age of the study group was 35.2 years. Post operatively, shoulder pendulum exercises were commenced on the second day and all patients discharged within 48 hours. During the first few weeks, we restricted shoulder abduction to 90 degrees. At the first postoperative follow up appointment at 2 weeks, average shoulder abduction was 30 degrees and forward elevation −40 degrees. This improved at 6 weeks to 85 degrees and 105 degrees respectively. The plates were removed at an average time interval of 11 weeks for the ACJ dislocations (range 8–12 weeks) and 15 weeks for the clavicle fractures (range 12–16 weeks). At three months after plate removal, we evaluated patients to measure the Visual Analogue Score(VAS) and Constant Score. The mean VAS was 1.4 (range 0–6) and the mean Constant score was 92 (range 72 to 98). Wound healing problems occurred in two patients, while two had a stress riser clavicle fracture. These had to be subsequently fixed with a Dynamic Compression Plate. One patient developed a superficial wound infection. Seven patients had problems due to impingement between the hook and the under surface of the acromion. A 45 year old female patient developed ACJ instability after plate removal. Radiographs revealed widening of the AC joint and some osteophyte formation. She went on to develop frozen shoulder which was treated with intensive physiotherapy. The AO hook plate represents an improvement over previous implants in treating injuries around the AC Joint. However, the need for a second operation to remove the plate remains a significant problem. Complications resulting from impingement were common in our patients and represent a major drawback of this implant.
Osteoarthritis and Cartilage, 2009
Objectives: To generate and validate a murine model of joint surface repair following acute mecha... more Objectives: To generate and validate a murine model of joint surface repair following acute mechanical injury. Methods: Full thickness defects were generated in the patellar groove of C57BL/6 and DBA/1 mice by microsurgery. Control knees were either sham-operated or non-operated. Outcome was evaluated by histological scoring systems. Apoptosis and proliferation were studied using TU-NEL and Phospho-Histone H3 staining, respectively. Type II collagen neo-deposition and degradation were evaluated by immunostaining using antibodies to the CPII telopeptide and C1,2C (Col2-3/4Cshort), respectively. Aggrecanases and matrix metalloproteinases (MMPs) activity were assessed by immunostaining for TEGE 373 and VDIPEN neo-epitopes. Results: Young 8-week-old DBA/1 mice displayed consistent and superior healing of the articular cartilage defect. Age-matched C57BL/6 mice repaired poorly and developed features of osteoarthritis (OA). Compared to C57BL/6, DBA/1 mice displayed a progressive decline of chondrocyte apoptosis, cell proliferation within the repair tissue, persistent type II collagen neo-deposition, less type II collagen degradation, less aggrecanases and more MMP-induced aggrecan degradation. Eight-month-old DBA/1 mice failed to repair, but, in contrast to agematched C57BL/6 mice, developed no signs of OA. Conclusion: We have generated and validated a murine model of cartilage regeneration in which the outcome of joint surface injury is strain and age dependent. This model will allow, for the first time, the dissection of different pathways involved in joint surface regeneration in adult mammals using the powerful technology of mouse genetics.
Open fractures and associated soft tissue injuries
Principles of fracture fixation
Renal Osteodystrophy
Journal of the American Academy of Orthopaedic Surgeons, 2006
The incidence of chronic renal disease is increasing, and the pattern of renal osteodystrophy see... more The incidence of chronic renal disease is increasing, and the pattern of renal osteodystrophy seems to be shifting from the classic hyperparathyroid presentation to one of low bone turnover. Patients with persistent disease also live longer than previously and are more physically active. Thus, patients may experience trauma as a direct result of increased physical activity in a setting of weakened pathologic bone. Patient quality of life is primarily limited by musculoskeletal problems, such as bone pain, muscle weakness, growth retardation, and skeletal deformity. Chronic renal disease also increases the risk of comorbidity, such as infection, bleeding, and anesthesia-related problems. Current treatment strategies include dietary changes, plate-and-screw fixation, and open reduction and internal fixation.
RESEARCH ARTICLE Open Access
Natriuretic peptide receptors regulate cytoprotective effects in a human ex vivo 3D/bioreactor model
MUSCULOSKELETAL SURGERY, 2019
Purpose The objective of this study is to evaluate the outcomes of total hip arthroplasty (THA) i... more Purpose The objective of this study is to evaluate the outcomes of total hip arthroplasty (THA) in patients with radiationrelated changes to the bone, and specifically whether there is a difference in outcomes between cemented and uncemented acetabular components. Methods A database search was performed to identify available studies reporting adults undergoing THA who have previously had pelvic irradiation. Data were extracted and analysed with respect to the use of cemented versus uncemented acetabular components. Statistical analysis was performed using the Chi-square test for independence. Results The all-cause revision rate was 24% in the cemented THA group (27/111), compared with 15% of uncemented THAs (22/143) (p = 0.073). Revision for acetabular aseptic loosening occurred in 16% of cases (18/111) in the cemented group and 10% (15/143) in the uncemented group (p = 0.178). Acetabular aseptic loosening was reported in 24% of cemented THAs (27/111) and 14% of uncemented THAs (20/143), which was statistically significant (p = 0.035). Not all of these went on to have revision THA. The Incidence of prosthetic joint infection was similar in both groups. Conclusion Overall outcomes appear to be better for uncemented THAs in post-radiotherapy patients, with a significantly lower rate of aseptic loosening and an appreciable (but not statistically significant) reduction in revision rate. The best outcomes seem to be associated with the use of acetabular reinforcement across both cemented and uncemented groups, but further work is needed to evaluate this.
Intramedullary Fixation of Forearm Fractures Comparison of Elastic Nails or K-Wires
Orthopaedic Proceedings, Mar 1, 2003
Staged management of high-energy proximal tibia fractures
PubMed, 2004
High-energy proximal tibia fractures are complicated by soft tissue compromise and this may resul... more High-energy proximal tibia fractures are complicated by soft tissue compromise and this may result in sub-optimal outcomes. There is a high association of open injuries, compartment syndromes, and vascular injuries with these bony disruptions. Surgical treatment of these injuries has been associated with significant complications such as infection, knee stiffness, malunion, loss of fixation, soft tissue failure, and amputations. The loss of fixation is an issue especially in the elderly, with failure associated with age more than sixty years, premature weight bearing, preoperative displacement, fracture fragmentation, and severe osteoporosis. The use of two-stage reconstruction for the treatment of distal tibia fractures has been successful in decreasing the complication rates, including wound compromise. The two stages involve: 1. stabilization of the injured limb with a bridging external fixator to allow the soft tissues to improve and recover and 2. definitive fixation for reconstruction of the articular surface and meta-diaphyseal fractures. The use of such a protocol has been proposed for high-energy proximal tibia fractures to decrease the high rate of soft tissue compromise associated with traditional open methods of treatment. The choice of definitive fixation may include plates, nails, or non-bridging external fixation.
Comparison of Outcomes and Complications of Hip Arthroscopy for Mixed Hip Disorders Between Adolescents and Adults: A Prospective Cohort Study
Orthopaedic Proceedings, Feb 21, 2018
Aim The current literature indicates that hip arthroscopy is safe in both adolescents and adults ... more Aim The current literature indicates that hip arthroscopy is safe in both adolescents and adults with good early outcomes but there are no available studies that directly compare the outcomes of this procedure for mixed indications between these two groups. Method This was a prospective cohort study of 102 consecutive supine hip arthroscopies in 96 patients (48 adolescent ( 18 hips), mean age 33.8 years) at a tertiary referral paediatric and adult university hospital followed-up for a minimum of two years. Patient demographics, indications for surgery, Modified Harris Hip (MHHS) and Non-Arthritic Hip (NAHS) scores, operative interventions and complications were recorded. Results At two-year follow-up, the MHHS improved from a mean of 55.3 to 87.5 (p Conclusion This study confirms that hip arthroscopy for mixed indications leads to good early outcomes with low complication rates in adolescent and adult patients. The incidence of pudendal nerve palsy in the adolescent group is however noted and is of concern.
Archives of Orthopaedic and Trauma Surgery, Mar 4, 2020
Purpose A potential method to relieve the pain from medial osteoarthritis of the knee is to offlo... more Purpose A potential method to relieve the pain from medial osteoarthritis of the knee is to offload the medial compartment. The Latella ™ Knee Implant is a novel device designed to offload the medial compartment. The objective of the Cotera-1 study was to evaluate the preliminary safety and feasibility of the Latella implant to treat patients with medial OA of the knee, by a 2-year follow-up of a prospective multicenter feasibility study (Cotera-1) performed in the Netherlands and UK Methods In this first-in-man study, 11 participants received the Latella implant and were followed for 2 years, documenting physician assessment, Patient-Reported Outcome (PRO) scoring (KOOS, IKDC, Kujala, SF-36); Patient Global Assessment (PGA), radiographic analysis and MRI analysis, complications, reoperation rate and hip-knee-ankle axis. Results The Latella Knee Implant system proved to be well tolerated and demonstrated a low-risk safety profile up to 24 months post-treatment. A responder analysis was performed of the subjects who still had the Latella implanted at 24-month time point (n = 9). Based on a MCID of eight for KOOS pain sub-scale, 78% of the subjects at the 24 month time point would be considered as responders. Similarly, based on improvement in the medial knee pain compared to baseline using the NRS scale of 1-10, 89% of the subjects at the 24-month time point would be considered as responders. Two patients were revised during follow-up: one for arthrofibrosis and one converted to TKA for progression of OA. Conclusions The early clinical experience with the Latella Knee Implant in this pilot feasibility study has been encouraging. It appears to be a safe implant with possible effect on medial OA. Additional studies need to be performed to assess the safety and efficacy of the procedure in a larger patient population.
Injury-international Journal of The Care of The Injured, May 1, 2003
Intramedullary fixation of children's diaphyseal forearm fractures is becoming the surgical techn... more Intramedullary fixation of children's diaphyseal forearm fractures is becoming the surgical technique of choice, in those cases that warrant surgical intervention. This method offers both technical advantages and patient benefits over alternative techniques and implants that have been used in the past. We present a two-centre study assessing the outcome of either Kirschner wires or elastic stable intramedullary nails (ESIN) as the method of fracture stabilisation in such diaphyseal forearm fractures. A total of 36 children underwent K-wire fixation and 24 children underwent ESIN fixation. All fractures united with no resultant subjective disability. The complication rate following K-wires was 16% and that following nail fixation 9%. Loss of forearm rotation was documented in four children in the K-wire group and three children stabilised with nails. These results confirm an excellent outcome following intramedullary fixation. We have demonstrated no difference in outcome between K-wires and ESIN, although the nails do offer some theoretical advantages.
The journal of bone and joint surgery, Apr 1, 2012
THU0023 A novel role for ELR+ CXC chemokine signaling in cartilage homeostasis
Annals of the Rheumatic Diseases, Jun 1, 2013
Background ELR+ CXC chemokine production is studied in arthritis and is thought to contribute to ... more Background ELR+ CXC chemokine production is studied in arthritis and is thought to contribute to inflammation leading to articular cartilage breakdown and arthritis pathology. However, healthy articular chondrocytes express their own chemokine receptors and ligands. The function of CXC chemokine receptors in these cells is puzzling as chondrocytes are encased in a dense extracellular matrix and are not known to migrate in vivo. Objectives This study aims to investigate the function of the CXCR1/2 signaling pathway in articular cartilage. Methods CXCR1/2 expression in adult human articular chondrocytes was confirmed by semi-quantitative RT polymerase chain reaction (RT-PCR), Western blot and immunohistochemistry. Combined and individual functionality of CXCR1 and CXCR2 was tested using an in vitro calcium mobilisation assay. Validated blocking antibodies and siRNA were used to inhibit CXCR1/2 signaling at receptor level. Pertussis toxin, PI3K inhibitors and intracellular calcium chelators were used to block signaling at intracellular levels. The highly sulphated proteoglycan content of chondrocyte micromasses was analysed using Alcian blue staining and spectrophotometric quantification. Chondrocyte gene expression was assessed using real time RT-PCR. CXCL6 and CXCL8 were detected in heparitinase digested, chondroitinase ABC digested and undigested paraffin sections of human articular cartilage from healthy and osteoarthritic donors by immunohistochemistry. Finally, 8 week old CXCR2-/- mutant BALB/C mouse knee joint paraffin sections were analysed using Safranin Orange staining, Chambers scoring and ImageJ histomorphometry. Results CXCR1/2 expression was confirmed in normal human articular cartilage. Individual blockade of either CXCR1 or CXCR2 did not inhibit downstream calcium mobilisation, indicating that CXCR1 and CXCR2 have more functional redundancy than that observed in neutrophils. CXCR1/2 signaling disruption at receptor level or by downstream blockade in chondrocytes resulted in reduced extracellular matrix sulphated glycosaminoglycan content and reduced expression of the chondrocyte differentiation markers COL2A1, Aggrecan, and SOX9. CXCL6 and CXCL8 were found in cartilage extracellular matrix in healthy tissue in distinct localisation patterns, which were disrupted in osteoarthritic tissue and following heparitinase digestion. In vivo analysis of 15 knockout and 15 wild type knees revealed that CXCR2-/- mice have significantly thinner epiphyseal growth plates and medial tibial plateaus, with a reduced sulphated proteoglycan content found in medial condyle articular cartilage. Conclusions Our findings indicate that CXCR1/2 signaling is in fact required for maintenance of phenotypic stability in articular chondrocytes. Interactions with heparan sulphate proteoglycans and distribution patterns of ligands within the ECM, and their disruption during pathology, indicate the presence of a homeostatic mechanism whereby CXC chemokines are retained within the articular cartilage matrix via interactions with heparan sulphate proteoglycans, where they maintain chondrocyte phenotypic stability via an autocrine/paracrine signaling mechanism. In vivo analysis suggests that CXCR1/2 signaling may be specifically required during periods of high chondrocyte turnover, including within the growth plate. Disclosure of Interest None Declared
Interlocked Nailing of the Femur with the Brooker–Wills Nail: Our Experience
Orthopaedic Proceedings, Mar 1, 2009
Intramedullary Nailing is now accepted as the standard treatment for most femoral diaphyseal frac... more Intramedullary Nailing is now accepted as the standard treatment for most femoral diaphyseal fractures. Most intramedullary nails are designed for proximal and distal locking with screws. We describe our experience with the Brooker Wills femoral nail. This nail is unique as distal fixation is achieved with as transverse fixator deployed through slots in the nail, a concept first enunciated by deCamargo in 1952. The fins of the fixator pierce the distal cortex when deployed thereby conferring rotational stability. The entire nail (including the proximal and distal fixation devices) can be inserted through a single proximal incision in the skin. We treated 17 patients with femoral shaft fractures using this system. 93% of the patients were males. Motor vehicle accidents accounted for 80 % of the fractures. Most fractures involved the middle third of the femur (54%), followed by distal third (33%) and proximal third (13%). 67 % of the fractures showed Winquist and Hansen Grade 3 or 4 comminution. All the nailings were performed in the supine position. Static locking was done in 16 cases. Post operative weight bearing was individualized with 86% of the patients bearing full weight before the end of 16 weeks. The average time to full weight bearing was 14 weeks. The mean time to union was 17.1 weeks, with proximal, middle and distal third fractures showing average healing times of 19, 15.6 and 18.8 weeks respectively. All the fractures united. There was one case of delayed union. Intra-operative complications included–inability to deploy the distal fixator in one case and unwinding of the reamer in another case. There was one case of superficial infection where a patient developed a sinus over the metallic fin of the distal fixation device, which had penetrated the cortex. This healed after the distal fixation device was removed. There was one case of proximal nail migration, but the fracture went onto union with some limb shortening. Results were evaluated using the scoring system devised by Sanders etal (1991). The functional criteria in their scoring system include- knee flexion, presence of pain, femur deformity, walking distance, stair climbing and pre injury functional status. We achieved excellent results in 53% of patients, good- 27%, fair–13 % and poor-7%. We feel that the main advantage of the Brooker Wills Nail is the ease of distal locking. This saves time and also leads to lower level of radiation exposure, as the image intensifier is sparingly used for distal locking. In fact, this nail is an attractive option in centres which lack an image intensifier. We achieved good results with this nailing system and feel that it is an acceptable alternative to other nailing systems with conventional locking systems with screws.
Annals of the Rheumatic Diseases, Feb 25, 2013
EWRR abstracts were detectable in connective tissue fibroblasts. In ossified osteophytes (grade 2... more EWRR abstracts were detectable in connective tissue fibroblasts. In ossified osteophytes (grade 2-5), resistin and visfatin and to a lower extend adiponectin were expressed by osteoblasts and resistin and visfatin by osteoclasts. In all osteophyte grades adiponectin was detectable in blood vessels and visfatin was found in about 50% of the chondrocytes. Osteoblast stimulation with adiponectin increased the release of the inflammatory mediators IL-6 (2.6-fold), IL-8 (4.9-fold), and MCP-1 (2.1-fold). In contrast, resistin led to a non-significant decrease of these factors. The osteoblast populations showed individual differences in the baseline expression of the analysed factors and in their responsiveness to adipocytokines. Conclusions The adiponectin and visfatin expression in osteophyte connective tissue and cartilage suggests their involvement in early osteophyte development. Resistin and visfatin in osteoblasts and osteoclasts in ossified osteophytes indicates a role in osteophyte formation at later stages. The stimulation of osteoblasts with adiponectin induces the release of inflammatory mediators. Therefore, the analysed adipocytokines most likely are involved in osteophyte formation at different stages and correspondingly affect cells of cartilage and bone formation to a different extent.
Osteoarthritis and Cartilage, Sep 1, 2008
Clavicular Hook Plate: Not an Ideal Implant
Orthopaedic Proceedings, Mar 1, 2009
The aim of our study was to assess the use of the Clavicular Hook Plate in treating acromio–clavi... more The aim of our study was to assess the use of the Clavicular Hook Plate in treating acromio–clavicular joint dislocations and fractures of the distal clavicle. The prospective study was carried out at two hospitals- a teaching hospital and a district general hospital. Between 2001 and 2004 a total of 37 patients with AC joint injuries and distal clavicle fractures were treated surgically with this device. Four of the patients had sustained a Neers Type 2 fracture of the distal clavicle, while 33 patients had acromio-clavicular joint dislocation (Rockwood Type 3 or higher). Mean age of the study group was 35.2 years. Post operatively, shoulder pendulum exercises were commenced on the second day and all patients discharged within 48 hours. During the first few weeks, we restricted shoulder abduction to 90 degrees. At the first postoperative follow up appointment at 2 weeks, average shoulder abduction was 30 degrees and forward elevation −40 degrees. This improved at 6 weeks to 85 degrees and 105 degrees respectively. The plates were removed at an average time interval of 11 weeks for the ACJ dislocations (range 8–12 weeks) and 15 weeks for the clavicle fractures (range 12–16 weeks). At three months after plate removal, we evaluated patients to measure the Visual Analogue Score(VAS) and Constant Score. The mean VAS was 1.4 (range 0–6) and the mean Constant score was 92 (range 72 to 98). Wound healing problems occurred in two patients, while two had a stress riser clavicle fracture. These had to be subsequently fixed with a Dynamic Compression Plate. One patient developed a superficial wound infection. Seven patients had problems due to impingement between the hook and the under surface of the acromion. A 45 year old female patient developed ACJ instability after plate removal. Radiographs revealed widening of the AC joint and some osteophyte formation. She went on to develop frozen shoulder which was treated with intensive physiotherapy. The AO hook plate represents an improvement over previous implants in treating injuries around the AC Joint. However, the need for a second operation to remove the plate remains a significant problem. Complications resulting from impingement were common in our patients and represent a major drawback of this implant.
Osteoarthritis and Cartilage, 2009
Objectives: To generate and validate a murine model of joint surface repair following acute mecha... more Objectives: To generate and validate a murine model of joint surface repair following acute mechanical injury. Methods: Full thickness defects were generated in the patellar groove of C57BL/6 and DBA/1 mice by microsurgery. Control knees were either sham-operated or non-operated. Outcome was evaluated by histological scoring systems. Apoptosis and proliferation were studied using TU-NEL and Phospho-Histone H3 staining, respectively. Type II collagen neo-deposition and degradation were evaluated by immunostaining using antibodies to the CPII telopeptide and C1,2C (Col2-3/4Cshort), respectively. Aggrecanases and matrix metalloproteinases (MMPs) activity were assessed by immunostaining for TEGE 373 and VDIPEN neo-epitopes. Results: Young 8-week-old DBA/1 mice displayed consistent and superior healing of the articular cartilage defect. Age-matched C57BL/6 mice repaired poorly and developed features of osteoarthritis (OA). Compared to C57BL/6, DBA/1 mice displayed a progressive decline of chondrocyte apoptosis, cell proliferation within the repair tissue, persistent type II collagen neo-deposition, less type II collagen degradation, less aggrecanases and more MMP-induced aggrecan degradation. Eight-month-old DBA/1 mice failed to repair, but, in contrast to agematched C57BL/6 mice, developed no signs of OA. Conclusion: We have generated and validated a murine model of cartilage regeneration in which the outcome of joint surface injury is strain and age dependent. This model will allow, for the first time, the dissection of different pathways involved in joint surface regeneration in adult mammals using the powerful technology of mouse genetics.
Open fractures and associated soft tissue injuries
Principles of fracture fixation
Renal Osteodystrophy
Journal of the American Academy of Orthopaedic Surgeons, 2006
The incidence of chronic renal disease is increasing, and the pattern of renal osteodystrophy see... more The incidence of chronic renal disease is increasing, and the pattern of renal osteodystrophy seems to be shifting from the classic hyperparathyroid presentation to one of low bone turnover. Patients with persistent disease also live longer than previously and are more physically active. Thus, patients may experience trauma as a direct result of increased physical activity in a setting of weakened pathologic bone. Patient quality of life is primarily limited by musculoskeletal problems, such as bone pain, muscle weakness, growth retardation, and skeletal deformity. Chronic renal disease also increases the risk of comorbidity, such as infection, bleeding, and anesthesia-related problems. Current treatment strategies include dietary changes, plate-and-screw fixation, and open reduction and internal fixation.
RESEARCH ARTICLE Open Access
Natriuretic peptide receptors regulate cytoprotective effects in a human ex vivo 3D/bioreactor model
MUSCULOSKELETAL SURGERY, 2019
Purpose The objective of this study is to evaluate the outcomes of total hip arthroplasty (THA) i... more Purpose The objective of this study is to evaluate the outcomes of total hip arthroplasty (THA) in patients with radiationrelated changes to the bone, and specifically whether there is a difference in outcomes between cemented and uncemented acetabular components. Methods A database search was performed to identify available studies reporting adults undergoing THA who have previously had pelvic irradiation. Data were extracted and analysed with respect to the use of cemented versus uncemented acetabular components. Statistical analysis was performed using the Chi-square test for independence. Results The all-cause revision rate was 24% in the cemented THA group (27/111), compared with 15% of uncemented THAs (22/143) (p = 0.073). Revision for acetabular aseptic loosening occurred in 16% of cases (18/111) in the cemented group and 10% (15/143) in the uncemented group (p = 0.178). Acetabular aseptic loosening was reported in 24% of cemented THAs (27/111) and 14% of uncemented THAs (20/143), which was statistically significant (p = 0.035). Not all of these went on to have revision THA. The Incidence of prosthetic joint infection was similar in both groups. Conclusion Overall outcomes appear to be better for uncemented THAs in post-radiotherapy patients, with a significantly lower rate of aseptic loosening and an appreciable (but not statistically significant) reduction in revision rate. The best outcomes seem to be associated with the use of acetabular reinforcement across both cemented and uncemented groups, but further work is needed to evaluate this.