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Biomedical subjects

N Rushton

Publications and source records attributed to N Rushton.

At least 37 records · Page 2Linked to original sources
PubMed2003

The response of macrophages to particles of resorbable polymers and their degradation products.

Alpha polyesters such as poly(L-lactide) and poly(glycolide) are biodegradable materials used in fracture fixation and they need to be assessed for problems associated with their degradation products. This study has compared cell responses to low molecular weight poly(L-lactide) particles, lactate monomer, poly(glycolide) particles and glycolic acid at cytotoxic and sub-cytotoxic concentrations. Murine macrophages were cultured in vitro and the release of lactate dehydrogenase (LDH), prostaglandin E(2) (PGE(2) and interleukin-1 alpha IL-1alpha was measured following the addition of particles or monomer. Experiments revealed that both the poly(L-lactide) and poly(glycolide) particles gave rise to dose dependent increases in LDH release and an increase in IL-1alpha and PGE(2) release. Comparisons of the poly(L-lactide) particles to the poly(glycolide) particles did not reveal any differences in their stimulation of LDH, IL-1alpha and PGE(2) release. The lactate and glycolate monomers did not increase PGE(2) or IL-1alpha release above control levels. There was no difference in biocompatibility between the poly(L-lactide) and poly(glycolide) degradation products both in particulate and monomeric form.

Journal Article↗
PubMed2003

Bone remodeling at the endocortical surface of the human femoral neck: a mechanism for regional cortical thinning in cases of hip fracture.

UNLABELLED: Endocortical remodeling and wall thickness (W.Th.) were measured in femoral neck bone from 12 female fracture cases (81.3 +/- 1.5 years) and 12 sex-matched controls (81.9 +/- 1.9 years). Regionally, osteoid and eroded surface were increased, whereas W.Th. was reduced. These processes likely contribute to cortical bone loss seen in hip fracture. INTRODUCTION: Because periosteal expression of alkaline phosphatase was similar between cases and controls, we hypothesized that the mechanism causing the marked femoral neck cortical thinning associated with hip fracture may be net endocortical bone loss. METHODS: Twelve female cases of femoral neck fracture (mean age = 81.3 +/- 1.5 years) and 12 age- and sex-matched postmortem controls (mean age = 81.9 +/- 1.9 years) were included in the study. Samples of their femoral neck bone were embedded in methyl methacrylate, sectioned at 10 microm, and stained with Solochrome cyanine R and Goldner's trichrome for the detection of osteoid (%OS/BS) and resorption surfaces (%ES/BS) respectively. In addition, wall thickness (W.Th.) and lamellar thickness (Lm.Th.) data were also collected from identifiable endocortical bone packets as a measure of formative potential. RESULTS AND CONCLUSIONS: %OS/BS was significantly elevated in the anterior (control = 3.4 +/- 0.7: fracture = 11.0 +/- 2.3; p = 0.0001), inferior (3.4 +/- 1.0: 9.9 +/- 3.0; p = 0.0009), and posterior quadrants (3.2 +/- 0.8: 9.1 +/- 2.3; p = 0.0021). Only for anterior region was increased %ES/BS demonstrated in the fracture group (2.8 +/- 0.6: 5.3 +/- 0.7; p = 0.055). W.Th. (mm) was reduced only in the inferior region of the fracture cases (control = 33.7 +/- 1.2: fracture = 30.6 +/- 0.9; p = 0.013), whereas Lm.Th. was also reduced inferiorly (control = 2.7 +/- 0.08: fracture = 2.5 +/- 0.08; p = 0.042). These data suggest that an endocortical remodeling imbalance involving reduced bone formation within inferior region coupled with elevated anterior resorption may make an important contribution to the cortical thinning observed in cases of femoral neck fracture.

Aged↗
PubMed2002

Improving risk assessment: hip geometry, bone mineral distribution and bone strength in hip fracture cases and controls. The EPOS study. European Prospective Osteoporosis Study.

Hip geometry and bone mineral density (BMD) have previously been shown to relate independently to hip fracture risk. Our objective was to determine by how much hip geometric data improved the identification of hip fracture. Lunar pencil beam scans of the proximal femur were obtained. Geometric and densitometric values from 800 female controls aged 60 years or more (from population samples which were participants in the European Prospective Osteoporosis Study, EPOS) were compared with data from 68 female hip fracture patients aged over 60 years who were scanned within 4 weeks of a contralateral hip fracture. We used Lunar DPX 'beta' versions of hip strength analysis (HSA) and hip axis length (HAL) applied to DPX(L) data. Compressive stress (Cstress), calculated by the HSA software to occur as a result of a typical fall on the greater trochanter, HAL, body mass index (BMI: weight/(height)2) and age were considered alongside femoral neck BMD (FN-BMD, g/cm2) as potential predictors of fracture. Logistic regression was used to generate predictors of fracture initially from FN-BMD. Next age, Cstress (as the most discriminating HSA-derived parameter), HAL and BMI were added to the model as potentially independent predictors. It was not necessary to include both HAL and Cstress in the logistic models, so the entire data set was examined without excluding the subjects missing HAL measurements. Cstress combined with age and BMI provided significantly better prediction of fracture than FN-BMD used alone as is current practice, judged by comparing areas under receiver operating characteristic (ROC) curves (p<0.001, deLong's test). At a specificity of 80%, sensitivity in identification was improved from 66% to 81%. Identifying women at high risk of hip fracture is thus likely to be substantially enhanced by combining bone density with age, simple anthropometry and data on the structural geometry of the hip. HSA might prove to be a valuable enhancement of DXA densitometry in clinical practice and its use could justify a more proactive approach to identifying women at high risk of hip fracture in the community.

Absorptiometry, Photon↗
PubMed2002

Osteocyte density in aging subjects is enhanced in bone adjacent to remodeling haversian systems.

The osteocyte is a candidate regulatory cell for bone remodeling. Previously, we demonstrated that there is a substantial (approximately 50%) loss of osteocytes from their lacunae in the cortex of the elderly femoral neck. Higher occupancy was evident in tissue exhibiting high remodeling and high porosity. The present study examines the distribution of osteocytes within individual osteonal systems at differing stages of the remodeling cycle. In 22 subjects, lacunar density, osteocyte density, and their quotient, the percent lacunar occupancy, was assessed up to a distance of 65 microm from the canal surface in six quiescent, resorbing, and forming osteons. In both forming (p = 0.024) and resorbing (p = 0.034) osteons, osteocyte densities were significantly higher in cases of hip fracture than controls. However, there were no significant between-group differences in lacunar occupancy. In both cases and controls, osteocyte density (p < 0.0001; mean difference +/-SEM: 157 +/- 34/mm2) and lacunar occupancy (p = 0.025; mean difference: 8.1 +/- 3.4%) were shown to be significantly higher in forming compared with quiescent osteons. Interestingly, resorbing systems also exhibited significantly elevated osteocyte density in both the fracture and the control group combined (mean difference 76 +/- 23/mm2; p = 0.003). Lacunar occupancy was also greater in resorbing compared with quiescent osteons (both groups combined: p = 0.022; mean difference: 5.7 +/- 2.3%). Elevated osteocyte density and lacunar occupancy in forming compared with quiescent systems was expected because of the likely effects of aging on quiescent osteons. However, the higher levels of these parameters in resorbing compared with quiescent systems was the opposite of what we expected and suggests that, in addition to their postulated mechanosensory role in the suppression of remodeling and bone loss, osteocytes might also contribute to processes initiating or maintaining bone resorption.

Aged↗
PubMed2002

Patterns of osteocytic endothelial nitric oxide synthase expression in the femoral neck cortex: differences between cases of intracapsular hip fracture and controls.

Evidence indicates that extensive amalgamation of adjacent resorbing osteons is responsible for destroying the microstructural integrity of the femoral neck's inferior cortex in osteoporotic hip fracture. Such osteonal amalgamation is likely to involve a failure to limit excessive resorption, but its mechanistic basis remains enigmatic. Nitric oxide (NO) inhibits osteoclastic bone destruction, and in normal bone cells its generation by endothelial nitric oxide synthase (eNOS, the predominant bone isoform) is enhanced by mechanical stimuli and estrogen, which both protect against fracture. To determine whether eNOS expression in osteocytes reflects their proposed role in regulating remodeling, we have examined patterns of osteocyte eNOS immunolabeling in the femoral neck cortex of seven cases of hip fracture and seven controls (females aged 68-96 years). The density of eNOS+ cells (mm(-2)) was 53% lower in the inferior cortex of the fracture cases (p < 0.0004), but was similar in the superior cortex. eNOS+ osteocytes were, on average, 22% further from their nearest blood supply, than osteocytes in general (p < 0.0001) and the nearest eNOS+ osteocyte was 57% further from its nearest canal surface (p < 0.0001). This differential distribution of eNOS+ osteocytes was significantly more pronounced in the cortices of fracture cases (p < 0.0001). We conclude that the normal regional and osteonal pattern of eNOS expression by osteocytes is disrupted in hip fracture, particularly at sites that are loaded most by physical activity. These results suggest that eNOS+ osteocytes may normally act as sentinels confining resorption within single osteons. A reduction in their number, coupled to an increase in their remoteness from canal surfaces, may thus permit the irreversible merging of resorbing osteons, and thus contribute to the marked increase in the fragility of osteoporotic bone.

Aged↗
PubMed2002

Testing bone substitutes in a small animal model of revision arthroplasty.

This study evaluated a modification of the rat-pin model to enable testing of bone substitute materials. The model was characterized using the ceramic, beta-tricalcium phosphate (betaTCP) as a filler. A 1 mm wide, 3.6 mm deep defect was created around a stainless steel (SS) implant in the proximal tibia of a rat. This defect was filled with a ceramic powder. Large particles (90-312microm) of betaTCP were mixed with Gelfoam to form a paste which was then molded around the proximal end of either an uncoated SS pin or a pin coated with hydroxyapatite (HA). The pin with its ceramic collar was then implanted into the proximal tibia of 16 male Sprague Dawley rats. Two animals with coated implants and two with uncoated implants were sacrificed at 3, 6, 14 and 26 weeks. Longitudinal sections of each tibia were stained with toluidine blue and labeled for tartrate resistant acid phosphatase (TRAP). There was initial fibrous tissue interposition around the implants which was completely remodeled around the HA coated pins but which persisted in apposition to the SS pins. The remodeling process peaked at 3 weeks around the HA coated pins and at 6 weeks around the uncoated implants. There was little remodeling around either implant by 26 weeks. There was considerable residual betaTCP present which was well tolerated as the particles were often encased in bone. The model has several characteristics of revision arthroplasty and the results demonstrate the suitability of this model for testing bone substitutes.

Journal Article↗
PubMed2002

Quality improvement for patients with hip fracture: experience from a multi-site audit.

PROBLEM: The first East Anglian audit of hip fracture was conducted in eight hospitals during 1992. There were significant differences between hospitals in 90-day mortality, development of pressure sores, median lengths of hospital stay, and in most other process measures. Only about half the survivors recovered their pre-fracture physical function. A marked decrease in physical function (for 31%) was associated with postoperative complications. DESIGN: A re-audit was conducted in 1997 as part of a process of continuing quality improvement. This was an interview and record based prospective audit of process and outcome of care with 3 month follow up. Seven hospitals with trauma orthopaedic departments took part in both audits. Results from the 1992 audit and indicator standards for re-audit were circulated to all orthopaedic consultants, care of the elderly consultants, and lead audit facilitators at each hospital. KEY MEASURES FOR IMPROVEMENT: Processes likely to reduce postoperative complications and improve patient outcomes at 90 days. STRATEGY FOR CHANGE: As this was a multi-site audit, the project group had no direct power to bring about changes within individual NHS hospital trusts. RESULTS: Significant increases were seen in pharmaceutical thromboembolic prophylaxis (from 45% to 81%) and early mobilisation (from 56% to 70%) between 1992 and 1997. There were reduced levels of pneumonia, wound infection, pressure sores, and fatal pulmonary embolism, but no change was recorded in 3 month functional outcomes or mortality. LESSONS LEARNT: While some hospitals had made improvements in care by 1997, others were failing to maintain their level of good practice. This highlights the need for continuous quality improvement by repeating the audit cycle in order to reach and then improve standards. Rehabilitation and long term support to improve functional outcomes are key areas for future audit and research.

Aged↗
PubMed2002

Endotoxin contamination of particles produces misleading inflammatory cytokine responses from macrophages in vitro.

Particulate prosthetic materials are often studied by adding them to monocytic cells in vitro and measuring the release of cytokines as an indicator of their inflammatory potential. Endotoxin is known to be a contaminant of particle preparations and also stimulates the release of cytokines. It is usual to use a proprietary endotoxin test to avoid erroneous results. Four different formulations of cement were found to be free from endotoxin using standard, gel-clot tests but stimulated different levels of release of cytokines from macrophages. These differences were explained when a more sensitive, kinetic endotoxin assay showed that release correlated with minor contamination with endotoxin. In a repeat experiment using cement particles with low or undetectable levels of endotoxin by kinetic assay, differences in the ability of the formulations to stimulate the release of cytokines were not seen. Endotoxin is adsorbed on to the surface of particles and it is this combination which stimulates increased release of cytokines. In both the above methods for determination of endotoxin, the water in which the particles had been soaked was examined rather than the particles directly. Further investigations showed that a kinetic assay directly on a particle suspension is the most sensitive method to measure contamination with endotoxin.

Adsorption↗
PubMed2002

Circulating levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in patients with severe head injury.

There is evidence to suggest that fractures heal more rapidly in patients with a head injury as a result of systemic factors released from the site of this injury. We have measured the circulating level of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) in serum because of their known involvement in the stimulation of the activity of osteoblasts and the healing of fractures. The serum level of IGF-1 was significantly lower in patients with both head injury and fracture and fracture only compared with that in healthy volunteers (p < 0.01 and p < 0.02, respectively). The level of IGFBP-3 was also significantly lower in patients with both head injury and fracture (p < 0.01). Our findings showed, however, that the level of IGF-1 and IGFBP-3 varied from week to week in both the patients and healthy control subjects. These results indicate that the levels of circulating IGF-1 and IGFBP-3 are unlikely to be responsible for the altered healing of fractures seen in conjunction with head injury.

Adolescent↗
PubMed2001

Osteocyte lacunar occupancy in the femoral neck cortex: an association with cortical remodeling in hip fracture cases and controls.

In adult humans, osteocytes die and disappear from their lacunae in the cortex of bones which remodel slowly, such as the proximal femur, and osteocyte death is particularly prevalent in the elderly. We have investigated the statistical determinants of osteocyte density in microscopic fields (0.71 mm2) within thin, complete femoral neck cross-sections cut from biopsies embedded in methyl methacrylate and stained with solochrome cyanine R. Lacunae were counted under phase contrast and osteocytes within lacunae were counted in the same fields under epifluorescence. The percentage of lacunae containing an osteocyte varied between 12.4% and 99.2%, according to subject and quadrantic region of the cortex examined. The microscopic determinants of field-specific osteocyte density included the porosity measured in the field itself and the regional measurement of the proportion of cortical canals bearing osteoid. There was significant variation between subjects and, within subjects, between cortical regions. Also the inferior region showed a significantly higher density of lacunae than the superior region (+8.2%; P = 0.013). However, cases of fracture were not significantly different from controls with respect to osteocyte lacunar occupancy after adjusting for osteoid-bearing canals and porosity. It is concluded that in subjects in their 7th-9th decades of age, osteocyte lacunar occupancy is statistically associated with bone turnover, implying that high turnover (locally young bone age) might favor lacunar occupancy (ln% osteoid; P = 0.021). Alternative explanations of the association are that porosity reflects a better nutritional supply via the vasculature or that porosity of the cortex is associated with osteocyte density through an effect of osteocytes on bone remodeling.

Aged↗
PubMed2001

In vitro and in vivo investigations into the biocompatibility of diamond-like carbon (DLC) coatings for orthopedic applications.

Diamond-like carbon (DLC) shows great promise as a durable, wear- and corrosion-resistant coating for biomedical implants. The effects of DLC coatings on the musculoskeletal system have not been investigated in detail. In this study, DLC coatings were deposited on polystyrene 24-well tissue culture plates by fast-atom bombardment from a hexane precursor. Two osteoblast-like cell lines were cultured on uncoated and DLC-coated plates for periods of up to 72 h. The effects of DLC coatings on cellular metabolism were investigated by measuring the production of three osteoblast-specific marker proteins: alkaline phosphatase, osteocalcin, and type I collagen. There was no evidence that the presence of the DLC coating had any adverse effect on any of the parameters measured in this study. In a second series of experiments, DLC-coated cobalt-chromium cylinders were implanted in intramuscular locations in rats and in transcortical sites in sheep. Histologic analysis of specimens retrieved 90 days after surgery showed that the DLC-coated specimens were well tolerated in both sites. These data indicate that DLC coatings are biocompatible in vitro and in vivo, and further investigations into their long-term biological and tribological performance are now warranted.

Alkaline Phosphatase↗
PubMed2001

Correlation of synovial fluid cytokine levels with histological and clinical parameters of primary and revision total hip and total knee replacements.

We retrieved synovial tissue and fluid samples from patients undergoing primary total hip replacement (THR) (n 15), revision of aseptically loose THR (n 12), primary total knee replacement (TKR) (n 13) and revision of aseptically loose TKR (n 6). Several histological parameters were assessed on a relative scale of 14. Primary TJRs were clinically evaluated for degree of osteoarthrosis. Revision TJRs were assessed for migration of the implant, gross loosening and the degree of radiolucency. Cytokine levels in synovial fluid were determined with ELISA. All cytokines were significantly higher in revision TJRs than in primary replacements, as were the degree of macrophage and giant cell infiltration. We found no relationship between any clinical variable and the levels of any cytokine, but migration of the implant was related to the presence of PE debris. A significant correlation was seen between the presence of macrophages and the levels of IL-1beta, IL-8 and IL-10, but not IL-6. No differences were noted between hips and knees for any of the variables, except in the levels of IL-6, where higher levels were found in THRs. These results suggest a unique role for IL-6 that requires further investigation.

Adult↗
PubMed2001

MR imaging of the wrist: effect on clinical diagnosis and patient care.

PURPOSE: To evaluate the effect of magnetic resonance (MR) imaging of the wrist on clinicians' diagnoses, diagnostic certainty, and patient care. MATERIALS AND METHODS: A controlled observational study was performed. Referring clinicians completed questionnaires about diagnosis and intended management before and after wrist MR imaging. One hundred eighteen consecutive patients referred for MR imaging of the wrist were recruited from the MR imaging units at a regional teaching hospital and a large district general hospital. The main measures were changes in the clinicians' leading and subsidiary diagnoses after MR imaging, their certainty in these diagnoses, and changes in intended patient care. RESULTS: Questionnaires were incorrectly completed for five patients, questionnaires were not returned for three, appointments were canceled for 10, and two could not tolerate the MR examination. Complete follow-up data were available for 98 patients. The clinical diagnosis changed in 55 of 98 patients; in the remaining 43 patients, diagnostic certainty increased in 23. Clinicians reported that MR imaging had substantially improved their understanding of the disease in 67 of 98 patients. The care plan changed in 45 of 98 patients, with a shift away from surgical treatment. Twenty-eight patients were discharged without further investigation. MR imaging was similarly effective in the regional teaching center and the district general hospital. CONCLUSION: MR imaging of the wrist influences clinicians' diagnoses and management plans.

Humans↗
PubMed2001

Tourniquet-induced wound hypoxia after total knee replacement.

We have investigated whether the thigh tourniquet used during total knee replacement (TKR) influenced the development of postoperative wound hypoxia and was a cause of delayed wound healing. We allocated randomly 31 patients (31 TKRs) to one of three groups: 1) no tourniquet; 2) tourniquet inflated at low pressure (about 225 mmHg); and 3) tourniquet inflated to high pressure of about 350 mmHg. Wound oxygenation was measured using transcutaneous oxygen electrodes. In the first week after surgery, patients with a tourniquet inflated to a high pressure had greater wound hypoxia than those with a low pressure. Those without a tourniquet also had wound hypoxia, but the degree and duration were less pronounced than in either of the groups with a tourniquet. Use of a tourniquet during TKR can increase postoperative wound hypoxia, especially when inflated to high pressures. Our findings may be relevant to wound healing and the development of wound infection.

Arthroplasty, Replacement, Knee↗
PubMed2001

Inflammatory responses of human primary macrophages to particulate bone cements in vitro.

We have investigated whether the particle-stimulated release of inflammatory cytokines from human primary macrophages in vitro was dependent upon the type of bone cement used. Particles of clinically relevant size were produced from Palacos R without radio-opacifier, Palacos R with BaSO4, Palacos R with ZrO2 and from CMW3 which contains BaSO4. All four preparations produced significantly greater release of tumour necrosis factor alpha, interleukin-6 and interleukin-1 beta than a negative control but there were no significant differences between them. The differences in the ability to stimulate bone resorption and in clinical performance between proprietary bone cements previously recorded are not explained by the release of the cytokines most commonly implicated in osteolysis.

Acrylic Resins↗
PubMed2001

The effects of particulate bone cements at the bone-implant interface.

We used a rat model in vivo to study the effects of particulate bone cements at the bone-implant interface. A ceramic pin was implanted into the tibiae of 48 rats. Three types of particle of clinically relevant size were produced from one bone-cement base without radio-opacifier, with zirconium dioxide (ZrO2) and with barium sulphate (BaSO4). The rats were randomly assigned to four groups to receive one of the three bone cements or normal saline with 2% v/v Sprague-Dawley serum as the control. A total of 10(9) particles was injected into the knee at 8, 10 and 12 weeks after the original surgery. The animals were killed at 14 weeks and the tibiae processed for histomorphometry. The area of fibrous tissue and the gap between the implant and bone were measured using image analysis. All three types of particle were associated with a larger area of bone resorption than the control. Only in the case of the BaSO4-containing cement did this reach statistical significance (p = 0.01). Particles of bone cement appear to promote osteolysis at the bone-implant interface and this effect is most marked when BaSO4 is used as the radiopaque agent.

Animals↗
PubMed2001

Intracapsular hip fracture and the region-specific loss of cortical bone: analysis by peripheral quantitative computed tomography.

Generalized bone loss within the femoral neck accounts for only 15% of the increase in intracapsular hip fracture risk between the ages of 60 and 80 years. Conventional histology has shown that there is no difference in cancellous bone area between cases of intracapsular fracture and age and sex-matched controls. Rather, a loss of cortical bone thickness and increased porosity is the key feature with the greatest change occurring in those regions maximally loaded during a fall (the inferoanterior [IA] to superoposterior [SP] axis). We have now reexamined this finding using peripheral quantitative computed tomography (pQCT) to analyze cortical and cancellous bone areas, density, and mass in a different set of ex vivo biopsy specimens from cases of intracapsular hip fracture (female, n = 16, aged 69-92 years) and postmortem specimens (female, n = 15, aged 58-95 years; male, n = 11, aged 56-86 years). Within-neck location was standardized by using locations at which the ratio of maximum to minimum external diameters was 1.4 and at more proximal locations. Cortical widths were analyzed using 72 radial profiles from the center of area of each of the gray level images using a full-width/half-maximum algorithm. In both male and female controls, cancellous bone mass increased toward the femoral head and the rate of change was gender independent. Cancellous bone mass was similar in cases and controls at all locations. Overall, cortical bone mass was significantly lower in the fracture cases (by 25%; p < 0.001) because of significant reductions in both estimated cortical area and density. These differences persisted at locations that are more proximal. The mean cortical width in the cases was significantly lower in the IA (22.2%;p = 0.002) and inferior regions (19%;p < 0.001). The SP region was the thinnest in both cases and controls. These data confirm that a key feature in the etiology of intracapsular hip fracture is the site-specific loss of cortical bone, which is concentrated in those regions maximally loaded during a fall on the greater trochanter. An important implication of this work is that the pathogenesis of bone loss leading to hip fracture must be by a mechanism that varies in its effect according to location within the femoral neck Key candidate mechanisms would include those involving locally reduced mechanical loading. This study also suggests that the development of noninvasive methodologies for analyzing the thickness and estimated densities of critical cortical regions of the femoral neck could improve detection of those at risk of hip fracture.

Aged↗