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Biomedical subjects

A J Carr

Publications and source records attributed to A J Carr.

At least 55 records · Page 3Linked to original sources
PubMed1998

Aromatic analogs of arcaine inhibit MK-801 binding to the NMDA receptor.

Aromatic analogs of arcaine were shown to have inhibitory effects on the binding of the channel blocking drug [3H]MK-801 to the NMDA receptor complex. The most potent compound of the series was an N,N'-bis(propyl)guanidinium which inhibited [3H]MK-801 binding with an IC50 of 0.58 microM and an IC50 of 12.17 microM upon addition of 100 microM spermidine. The increase in IC50 upon addition of spermidine suggests competitive antagonism between the inhibitor and spermidine at the arcaine-sensitive polyamine site of the NMDA receptor complex.

Biguanides↗
PubMed1998

A quantitative study of the sintering and mechanical properties of hydroxyapatite/phosphate glass composites.

Previous work has shown that small additions of a phosphate glass (CaO-P2O5) can significantly enhance the sinterability and strength of hydroxyapatite. However, there are no quantitative phase analyses available for these materials which would provide indicators of biocompatibility and resorbability. Similarly, there is little information available about the mechanical properties, especially with high glass additions. In this study, the effects of sintering hydroxyapatite with phosphate glass additions of 2.5, 5, 10, 25, and 50 wt.% are quantified. Each composition was sintered over a range of temperatures, and quantitative phase analysis was carried out using XRD. In addition, the microstructures were studied using RLOM and SEM, and mechanical properties (Vickers hardness, KIC, and MOR) measured. These results may be used to indicate which compositions and processing conditions may provide materials suitable for use in hard tissue replacement. Composites containing up to 10 wt.% glass additions formed dense HA/TCP composite materials possessing flexural strength and fracture toughness values up to 200% those of pure HA. The HA/TCP ratio was strongly dependent on the percentage glass addition. Higher glass additions resulted in composites containing beta-TCP together with large amounts of alpha- or beta-calcium pyrophosphate, and having similar mechanical strengths to pure HA.

Biocompatible Materials↗
PubMed1998

A synthetic bone implant macroscopically identical to cancellous bone.

Macroporous hydroxyapatite (HA) and beta-tricalcium phosphate (beta-TCP) are widely used as synthetic bone replacement materials due to their high biocompatibility and osteoconductive properties. The level of porosity, pore size distribution, pore morphology, and the degree of pore interconnectivity in such grafts significantly influences the extent of bone ingrowth. It has been hypothesised that an ideal implant macrostructure may be similar in morphological characteristics to the inorganic matrix of the bone it is replacing. However, to date, clinically available synthetic materials differ structurally from cancellous bone. A method is described for the macrostructural replication of cancellous bone. Reproduction involves a multistage process requiring the manipulation of positive and negative forms of the inorganic matrix. By infiltration of a wax negative mould of cancellous bone with a ceramic slip, followed by removal of the wax, and firing, it is possible to produce a positive replica of the original cancellous macrostructure. Optimisation of slip preparation conditions (pH and percentage deflocculant addition) and sintering conditions have allowed successful replication of cancellous bone using several bioceramic compositions including HA, beta-TCP, and HA/beta-TCP.

Bone Substitutes↗
PubMed1998

Development of a new synthetic bone graft.

A process for the replication of bovine cancellous bone in synthetic bioceramic materials for use as artificial bone graft substitutes is described. The process detailed here may be easily implemented to allow production of large numbers of blocks of material, even on a laboratory scale. The graft material has a pore morphology and interconnectivity identical with that of the original cancellous bone used as a starting material. Strength of the material is adequate, and at lower porosity levels it meets the FDA requirements for coralline materials for spinal applications. The synthetic graft is also shown to have excellent fluid-retention characteristics, making it a potential carrier for morphogenic agents such as solutions of bone morphogenic protein.

Journal Article↗
PubMed1998

Patients with primary osteoarthritis show no change with ageing in the number of osteogenic precursors.

The variation in marrow colony forming unit-fibroblastic (CFU-F) number in 59 patients (14-87 years of age) undergoing corrective surgery (14 controls; 14-48 years of age) or hip arthroplasty for primary osteoarthritis (45 OA; 46-87 years of age) was examined to determine whether marrow CFU-F, derived from marrow stromal fibroblastic stem cells, are maintained with the development of primary osteoarthritis (OA). Total colony number, colony size as well as alkaline phosphatase-positive colonies were determined. The mean fibroblast colony forming efficiency from the whole patient group was 2.4 x 10(-5) +/- 1.4 x 10(-5). Ageing had no effect on the colony forming efficiency or on the alkaline-phosphatase-positive colony forming efficiency, irrespective of gender. Thus precursor cells with the potential for osteogenic differentiation are maintained in OA with ageing. However, colony size showed a significant reduction with age, implying altered proliferation potential of osteogenic progenitors with ageing. This ageing effect may not be as significant in OA as in the rest of the population as bone mineral density is often preserved in osteoarthritis. As there is no apparent deficit in primitive progenitor cells, this preservation may be the result of altered regulation of osteoprogenitor activity in OA.

Adolescent↗
PubMed1997

Anatomy of the normal acromion investigated using MRI.

The shape of the acromion is strongly associated with impingement syndrome and with rotator cuff tears. It is notoriously difficult to image the acromion with conventional radiography. We have developed MRI techniques to depict the acromion in its longitudinal axis. Furthermore, we have measured the subacromial space in both external and internal rotation. In previous studies, three types of acromial shape have been described with the type III or hooked acromion being present in 66% of cases with rotator cuff tears. We studied 31 normal shoulders in 29 people using MRI. Within this population aged 24-36 years, mean age 31 years, no type III acromions were found. Twenty-one were type I (67.7%) and 10 were type II (32.3%). In addition, we found no difference in subacromial height in external or internal rotation. Low rates of intra- and interobserver error were found. These results imply that the hooked acromion is not present in the normal population and is, therefore, likely to be an acquired abnormality.

Acromion↗
PubMed1997

Measurement of the anteroposterior translation of the humeral head using MRI.

Anteroposterior translation of the humeral head within the glenohumeral joint was investigated using MRI. Ten normal shoulders, 11 recurrent anterior dislocations, 10 stabilised shoulders after the Putti-Platt operation and one shoulder with multidirectional instability, were scanned. The arm was positioned in internal and external rotation and in an overhead position. Gradient echo volume acquisition scans were carried out, and 22 were suitable for evaluation. Consistent results were obtained in the normal shoulders. The unstable and unstable shoulders showed higher variance, but there was no significant anterior translation in external rotation in any group. The range of external rotation was significantly reduced in the unstable and stabilised shoulders. A trend towards posterior translation was found in internal rotation with a mean of 1 (+/- 0.44) in normal, 0.89 (+/- 1.67) in unstable and 1.6 (+/- 1.4) in stabilised shoulders.

Adolescent↗
PubMed1997

Genetic influences in end-stage osteoarthritis. Sibling risks of hip and knee replacement for idiopathic osteoarthritis.

From a prospective, cross-sectional survey of 402 patients who had a total hip (THR) or a total knee (TKR) replacement for idiopathic osteoarthritis (OA) at a major centre, we determined the prevalence of these replacements for idiopathic OA in their 1171 siblings and 376 spouses. Using spouses as controls, the relative risk of THR in siblings was 1.86 (95% CI 0.93 to 3.69). The relative risk for TKR in siblings v spouses was 4.8 (95 % CI 0.64 to 36.4) whereas the risk for the combined outcome measure of THR or TKR was 2.32 (95% CI 1.22 to 4.43) when siblings and spouses over 64 years of age were compared. Using a threshold liability model (Falconer), the heritability of end-stage OA of the hip was estimated at 27%. The increased risks of joint replacement for severe, idiopathic OA which we found in siblings suggest that genetic influences are important in end-stage OA of the hip and knee.

Adult↗
PubMed1997

Synovectomy of the elbow and radial head excision in rheumatoid arthritis. Predictive factors and long-term outcome.

We carried out a survival analysis of elbow synovectomy (ES) and excision of the radial head (RHE) performed on 171 rheumatoid elbows. The failure criteria were revision surgery (performed or desired) and/or the presence of significant or severe pain. The cumulative survival was 81% at one year which thereafter decreased by an average of 2.6% per year. The strongest predictor for success was a low preoperative range of supination-pronation when corresponding survival curves were compared. A low range of flexion-extension also predicted failure. Combining both factors gave better prediction (failure: 6.3% v 67%), but a long duration of elbow symptoms before surgery predicted failure (72%, p = 0.04). At review, there was a mean gain of 50 degrees in supination-pronation and 11 degrees in flexion-extension; both correlated with success. Failure correlated with recurrence of synovitis, elbow instability, ulnar neuropathy, poor general mobility and poor upper-limb function. The last was independently affected by the severity of RA in the ipsilateral shoulder. Our findings show that although the short-term result of ES and RHE in rheumatoid arthritis is good, the long-term outcome is poor except in a subgroup with more than 50% limitation of forearm rotation.

Adult↗
PubMed1996

Margaret Holroyd Prize Essay. A patient-centred approach to evaluation and treatment in rheumatoid arthritis: the development of a clinical tool to measure patient-perceived handicap.

Assessment of patient-centered outcomes is of particular importance in a chronic disease such as rheumatoid arthritis (RA), where a major aim of treatment is a reduction of its disabling and handicapping effects. Rheumatology is reasonably well advanced in its deployment of such outcomes. Measurement of the patient's experience of disease has focused on the ability to perform daily living tasks and, latterly, on the more global effect on quality of life. Neither of these approaches is without conceptual and measurement problems. A new measure of patient-centred outcome in RA has been developed (Carr AJ, Br J Rheumatol 1994;33:378-82). This tool, the Disease Repercussion Profile (DRP), attempts to extend the measurement of outcome to incorporate the individual functional, social, psychological, emotional and economic disadvantage resulting from RA, i.e. patient-perceived handicap. It has been designed for use as a clinical tool, to allow patients to specify the problems and needs of most importance to them, and as such represents a new approach. This paper reviews the development of the DRP in the context of existing health status measures and examines its potential role as a routine measure in an out-patient setting.

Arthritis, Rheumatoid↗
PubMed1996

Quality of life measures.

Quality of life measures have become increasingly popular as outcome measures despite the lack of consensus on a definition of quality of life. This review describes the most frequently used measures, and discusses the conceptual and measurement issues surrounding quality of life measurement. Finally, it tries to place quality of life in the World Health Organization's model of disease impact.

Disability Evaluation↗
PubMed1996

Handicap in inflammatory arthritis.

Two instruments measuring handicap were evaluated and compared with clinical, laboratory and disability measures. Participants were 133 patients attending a rheumatology follow-up clinic in a district general hospital, of whom 102 were followed up after 3 months. Measurements included acute-phase response, early morning stiffness, pain, wellbeing, joint involvement (impairments), the Stanford Health Assessment Questionnaire (disability), the Disease Repercussion Profile and the London Handicap Scale (handicap). A substantial burden of disability and handicap was recorded. There were moderate correlations between impairments (0.4 < rho < 0.6), and moderate to strong correlations between disability and handicap measures (0.4 < rho < 0.8). Correlations between impairment and disability/handicap were weak (rho < 0.4). Mean changes in all variables over 3 months were small, and none was statistically significant. A comprehensive description of the impact of disease and treatment requires measurements to be made of impairments, disabilities and handicaps. The use of clinical and laboratory variables alone may be misleading.

Adult↗
PubMed1996

An evaluation of the Constant-Murley shoulder assessment.

We have analysed the Constant-Murley (1987) assessment for 25 patients with shoulder pathology. We found the score easy to use, with low inter- and intraobserver errors, but sufficiently imprecise in repeated measurements to give concern in its use for clinical follow-up of patients. We have calculated 95% confidence limits for a single assessment to be within 16 to 20 points in most cases. In addition, we found that all our subjects with instability as their main problem scored within five points of the maximum; this suggests that the scoring method may need to be revised for use on these patients.

Confidence Intervals↗
PubMed1995

Fibrogenesis imperfecta ossium.

The clinical features, investigation, treatment and outcome of two adults with fibrogenesis imperfecta ossium are described. In this rare acquired disorder of bone, normal lamellar collagen is replaced by structurally unsound collagen-deficient tissue, which leads to extreme bone fragility and ununited fractures. Transmission microscopy and SEM showed striking ultrastructural changes in bone structure and mineralisation. Both patients had monoclonal IgG paraproteins in the plasma and one excreted monoclonal lambda light chains in the urine. No abnormal plasma cells were found in the bone marrow and there was no evidence of amyloid deposition in the tissues. In both patients initial treatment with 1 alpha-hydroxycholecalciferol appeared to be ineffective, but in one, repeated courses of melphalan and corticosteroids over three years together with 1 alpha-hydroxycholecalciferol produced striking clinical and histological improvement. The findings in these and other patients strongly suggest that paraproteinaemia is an integral feature of fibrogenesis imperfecta ossium, and this needs further investigation.

Adrenal Cortex Hormones↗
PubMed1995

Which primary total hip replacement?

To assist surgeons to select a total hip replacement (THR) we present comparative information on all such implants on the market in the UK. We identified 62 different primary THRs, manufactured by 19 companies; half had been introduced in the last five years, and only 30% have any results published in peer-reviewed journals. The prices range from 250 pounds to 2000 pounds, and the two cheapest implants have the longest reported follow-up. The number of THR implants available in the UK, and presumably the rest of the world, is rapidly increasing, but there is little or no scientific evidence that the newer, more expensive, implants are better than established designs. Some will undoubtedly be worse. We believe that this situation is unsatisfactory and make recommendations for improvement, in particular that preference be given to implants with good results in published peer-reviewed long-term clinical trials.

Evaluation Studies as Topic↗