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Hamish Simpson

Publications and source records attributed to Hamish Simpson.

10 recordsLinked to original sources
PubMed2006

The role of inhibitory molecules in fracture healing.

The balance between all the signalling molecules involved in bone formation with their inhibitors and most importantly between BMPs and their antagonists is critical determinant of osteogenesis, and therefore of skeletal development, fracture repair, and bone remodelling. The main identified inhibitory molecules of the osteogenic lineage, either from studies during embryonic development or from in vitro and in vivo studies are presented in the herein study. Potential treatments using these molecules either alone or in combination with BMPs to control the bone growth and overgrowth are already under investigation aiming in treatments that mimic as much as possible the natural process of bone generation in various situations including fracture healing, osteoporosis, and osteoarthritis and other metabolic disorders, in order to more closely resemble the original tissue.

Animals↗
PubMed2006

Staphylococcus aureus capsular material promotes osteoclast formation.

Osteomyelitis, which is most frequently due to infection by Staphylococcus aureus, commonly causes bone destruction. S. aureus is known to secrete a number of surface-associated proteins that are potent stimulators of bone resorption. The precise cellular and humoral mechanisms that mediate this stimulatory effect are uncertain. In this study, we have determined whether osteoclast formation and resorption is directly promoted by surface-associated proteins. Surface-associated material (SAM) obtained from a 24-hour culture of S. aureus was added to cultures of mouse and human monocytes. Human monocyte cultures were incubated in the presence and absence of a soluble receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage colony stimulating factor (M-CSF). In cultures where M-CSF, RANKL, and SAM were added together, osteoclast formation did not exceed that seen in cultures with M-CSF and RANKL. In keeping with this finding, SAM did not increase osteoclast formation and resorption when mouse monocytes were cocultured with RANKL-expressing osteoblasts. In the absence of RANKL, however, SAM was capable of inducing osteoclast formation in cultures of human monocytes. This finding was evidenced by the generation of vitronectin receptor and tartrate-resistant acid phosphatasepositive multinucleated cells that were capable of lacunar resorption. Inhibitors of RANKL-dependent (RANK:Fc, OPG) and RANKL-independent (anti-TNF-alpha, gp130, IL-8, TGF-beta) osteoclast formation did not inhibit SAM-induced osteoclast formation. SAM did not stimulate mature osteoclast resorption activity. These findings indicate that RANKL, which is present in the circulation as a soluble factor, does not play a role in osteoclast formation in the presence of S. aureus SAM and that S. aureus SAM contains a soluble factor that promotes osteoclast formation by a RANKL-independent mechanism.

Animals↗
PubMed2004

Multinational survey of osteoporotic fracture management.

Osteoporosis is characterized by a decreased bone mass and an increased bone fragility and susceptibility to fracture. Patients with a fragility fracture at any site have an increased risk of sustaining future fractures. Orthopedic surgeons manage most of these fractures and are often the only physician seen by the patient. Mounting evidence that orthopedic surgeons are not well attuned to osteoporosis led the Bone and Joint Decade (BJD) and the International Osteoporosis Foundation (IOF) to survey 3,422 orthopedic surgeons in France, Germany, Italy, Spain, the United Kingdom, and New Zealand. The majority of the respondents in all countries had the opinion that the orthopedic surgeon should identify and initiate the assessment of osteoporosis in patients with fragility fractures. Heterogeneous practice pattern exist in different countries; however, identification and treatment of the osteoporotic patient seems to be insufficient in many areas: half of the orthopedic surgeons surveyed received little or no training in osteoporosis. Only approximately one in four orthopedic surgeons in France, the UK and New Zealand regarded themselves as knowledgeable about treatment modalities. Less than one-fifth of the orthopedic surgeons arranged for a surgically treated patient with a fragility fracture to have a bone mineral density (BMD) test. Twenty percent said that they never refer a patient after a fragility fracture for BMD. Only half of the orthopedic surgeons in southern Europe know about the importance of some external risk factors for hip fractures (cataracts, poor lighting, pathway obstacles, poor balance). In summary, this survey clearly indicates that many orthopedic surgeons still neglect to identify, assess and treat patients with fragility fractures for osteoporosis. More educational opportunities need to be offered to orthopedic surgeons through articles, web-based learning and educational seminars. Development of a simple clinical pathway from evidence-based guidelines is an important step to ensure that optimal care is provided for patients with fragility fractures.

Attitude of Health Personnel↗
PubMed2003

Rapid new bone tissue remodeling during distraction osteogenesis is associated with apoptosis.

During the process of distraction osteogenesis new bone forms and undergoes rapid remodeling. Apoptosis may be one of the regulatory mechanisms governing the removal of the redundant callus during distraction osteogenesis. A rabbit tibial lengthening model was used and lengthened at 0.7 mm/day for 3 weeks. The regenerating tissues from the distraction gap were examined for apoptotic changes by transmission electron microscopy (TEM) and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method. Osteoclastic bone resorption activities were demonstrated by tartrate resistant acid phosphatase (TRAP) staining. The apoptotic cells were mainly present in the transitional regions between the fibrous tissue and the new bone in the mineralization front, and close to or on the new bone surfaces near the center of the regenerate. The TUNEL labeling was greatly reduced in the mature bone near the osteotomied bone ends. TEM examination confirmed the presence of cells with apoptotic changes at various regions of the regenerate. TRAP staining revealed that osteoclastic bone resorption activities in the regenerate were in a similar pattern of distribution to those of the TUNEL labeling. The localization of apoptotic cells at the different regions of the regenerate, accompanied by the osteoclast activities, suggest that apoptosis is closely related to bone formation and remodeling during distraction osteogenesis.

Animals↗
PubMed2002

Bone consolidation is enhanced by rhBMP-2 in a rabbit model of distraction osteogenesis.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a differentiation factor which has been shown to induce bone formation and heal bony defects in a variety of animal models. A possible application of rhBMP-2 is to accelerate bone regeneration during distraction osteogenesis. which clinically is a long procedure, often involving significant complications. In this study we tested the ability of rhBMP-2 to accelerate the consolidation phase of distraction osteogenesis in a rabbit model of leg lengthening. Tibiae were lengthened 2 cm over a period of ten days. rhBMP-2 was administered at the end of the lengthening phase. Two modes of rhBMP-2 application were tested: surgical implantation of rhBMP-2/ACS (absorbable collagen sponge) into the regenerate (50 microl of 1.5 mg/ml rhBMP-2, total dose = 75 microg rhBMP-2), and percutaneous injection of rhBMP-2/buffer (0.1 ml of 0.75 mg/ml rhBMP-2. total dose = 75 microg rhBMP-2) into three sites within the regenerate. Also, there were three groups of control animals: (1) no surgical intervention, (2) surgical implantation of buffer/ACS and (3) percutaneous injection of buffer. Rabbits were sacrificed at 5, 14 and 28 days after the interventions. Radiographic evaluation indicated a significant increase in bony union of the distraction regenerate in the rhBMP-2 treated groups compared with the untreated groups at 5 and 14 days. At 28 days, formation of a cortex and reestablishment of the medullary canal was evident only in the rhBMP-2 treated groups. The bone mineral content (BMC) of the regenerate was significantly higher in the rhBMP-2 treated groups at 5 and 14 days. However, at 28 days, BMC of the regenerate was similar in all groups. The average volumetric density of the regenerate was significantly higher in the rhBMP-2 injection group at day 14. In Summary, both injection of rhBMP-2/buffer and implantation of rhBMP-2/ACS enhanced the consolidation stage of distraction osteogenesis in this rabbit model.

Animals↗
PubMed2002

Gene expression in response to muscle stretch.

In studying the way the musculoskeletal system adapts, it is important to consider how the different tissues interact with each other. During growth, and in response to changes in posture, the functional length of muscle is adjusted by altering the number of sarcomeres in series to the optimum for force generation and power output. In some cases, insufficient adaptation gives rise to problems such as muscle contracture. Stretch has marked effects on muscle mass with eccentric contraction being the most effective form of exercise for building muscles. As far as the mechanism is concerned, the current authors have cloned the deoxyribonucleic acid (cDNA) of a splice variant of the insulinlike growth factor gene that is produced by active muscle that seems to be the factor that controls local tissue repair, maintenance, and remodeling. This new growth factor has been called mechanogrowth factor to distinguish it from the liver insulin growth factors, which have a systemic mode of action. The discovery of the locally produced insulinlike growth factor seems to provide the link between the mechanical stimulus and the activation of gene expression.

Adaptation, Physiological↗
PubMed2002

Effect on knee flexion of a modification to the surgical technique of pin placement during femoral lengthening.

Loss of knee movement is a common problem in femoral lengthening. Two groups of 10 children were compared: one group lengthened by the Ilizarov technique using a standard method and one group in whom the technique was modified to incorporate a different method for determining the pin placement. Loss of knee flexion was compared between the two groups. A significant difference in the total loss of flexion ( <0.002), and in the amount of knee flexion, at the end of lengthening ( <0.001) and at 6 months after frame removal ( <0.004) was observed. This simple modification to surgical technique appears to decrease the knee flexion lost in children undergoing femoral lengthening by the Ilizarov method.

Adolescent↗
PubMed2002

Towards evidence based emergency medicine: best BETs from Manchester Royal Infirmary. Routine use of antibiotic ointment and wound healing.

A short cut review was carried out to establish whether topical antibiotics improved the outcome of simple wounds. Altogether 71 papers were found using the reported search, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of this best paper are tabulated. A clinical bottom line is stated.

Anti-Bacterial Agents↗
PubMed2002

Funding the NHS.

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Costs and Cost Analysis↗