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Biomedical subjects

D Murray

Publications and source records attributed to D Murray.

At least 37 records · Page 2Linked to original sources

A correlative study of clinical and histological findings of revision hip arthroplasty for rheumatoid arthritis and inflammatory joint disease.

OBJECTIVE: Primary hip arthroplasty in rheumatoid arthritis (RA) and other forms of inflammatory joint disease (IJD) is generally thought to be associated with a less favourable outcome in terms of implant survival and other complications. Whether the duration of implant survival correlates with the degree of rheumatoid-like inflammatory changes in periprosthetic tissues is uncertain. METHODS: Histopathological changes in periprosthetic tissues obtained following revision surgery of 34 total hip replacements on 27 patients with IJD (RA 18 cases: ankylosing spondylitis three cases; juvenile chronic arthritis six cases) were examined. RESULTS: A heavy diffuse lymphocyte and plasma cell infiltrate +/- lymphoid aggregates was noted in 29% of cases in whom the mean implant survival was 5.6 years (range: 2-8 years). Where little or no lymphocytic infiltrate was noted in periprosthetic tissues, the mean implant survival was 8.6 years (range: 1-17 years). Revision arthroplasty was not undertaken for early or late infection of a primary hip replacement. CONCLUSIONS: Our findings indicate that implant survival is less in those cases where there is a heavy lymphocyte and plasma-cell infiltrate in periprosthetic tissues. These findings suggest that the presence of a heavy chronic inflammatory-cell infiltrate in periprosthetic tissues is likely to be a contributory factor in causing early implant failure in RA.

Adolescent↗

Deep vein thrombosis in a tiler wearing tight knee pads.

Venous compression is a rare but accepted cause of Deep Venous Thrombosis. We report a case of DVT caused by extrinsic compression of the popliteal vein by constricting elasticated knee pads. The knee pads were worn at work by a Tiler who did not have any hypercoagulability disorder.

Adult↗

Does flying after myringoplasty affect graft take rates?

Flying at altitude soon after myringoplasty may theoretically have an adverse effect on graft take rates owing to variation in external air pressure, together with suboptimal Eustachian tube function, causing graft displacement. We wished to assess the effect of flying after myringoplasty by comparing success rates of patients flying within a week postoperatively (n = 37) with a control group (n = 37) by carrying out a retrospective, controlled cohort study. The primary outcome measure was graft success, defined as a 100% closure at first outpatient follow-up (2.5 months). Our results showed that there was no difference in early graft success rates between the flying group (32/37: 86%) and non-flying group (29/37: 78%)(P = 0.32; 95% CI of difference: -9% to 27%). In conclusion, flying at altitude in a pressurized environment within a week of myringoplasty does not adversely affect early operative success.

Adolescent↗

In vitro evaluation of the resistance to dislocation of a meniscal-bearing total knee prosthesis between 30 degrees and 90 degrees of knee flexion.

An increased incidence of dislocation is the most important potential disadvantage introduced by the use of meniscal-bearing prostheses. The aim of this in vitro study was to measure the resistance to dislocation of a meniscal-bearing total knee arthroplasty in various circumstances and to establish which anatomic structures contribute to bearing stability. The prosthesis was implanted into cadaver knee specimens mounted in a 6 df rig. Dislocation was provoked by applying anteriorly or posteriorly directed forces (20-100N) to the tibia in the plane of the tibial plateau. Dislocation was defined as any stable displacement of the bearing (relative to the tibia or the femur) that persisted after release of the load applied to provoke it. The specimens were tested in an arc of knee flexion between 30 degrees and 90 degrees, with and without simulated quadriceps loads, with and without abducting and adducting loads, and before and after division of the posterior cruciate ligament and the lateral retinaculum. In the presence of quadriceps load, dislocation could not be provoked. In the absence of quadriceps load, dislocation was not provoked by posteriorly directed force but sometimes was caused by anteriorly directed force. All but 1 of the dislocations were unicompartmental, the lateral compartment proving much less stable than the medial. The tendency toward dislocation increased from 30 degrees to 60 degrees and from 60 degrees to 90 degrees of knee flexion. Adducting moments applied to the knee caused lift-off of the lateral femoral condyle from the bearing and increased the tendency toward dislocation. Abducting moments had the opposite effect. Division of the posterior cruciate ligament had no significant effect. Division of the lateral retinaculum increased the tendency toward dislocation. A femoral component that can be implanted without lateral release is desirable.

Cadaver↗

Serum levels of cobalt and chromium in a complex modular total hip arthroplasty system.

There is concern that modularity in a total hip arthroplasty system increases serum cobalt and chromium ion levels. This study measures the serum cobalt and chromium levels in patients with an Oxford Universal Hip (Corin, Cirencester, United Kingdom), which has a modular sliding mechanism; patients with a similarly manufactured hip with no sliding mechanism; and a control group. Loosening was excluded clinically and radiologically. Arthroplasty patients had statistically higher levels of serum cobalt and chromium than controls, but there was no significant difference in levels between the implanted groups.

Arthroplasty, Replacement, Hip↗

Human herpesvirus 8 (HHV-8) detected in two patients with Kaposi's sarcoma-like pyogenic granuloma.

AIMS: To report the finding of human herpesvirus 8 (HHV-8) in two patients with Kaposi's sarcoma (KS)-like pyogenic granuloma. This form of pyogenic granuloma closely resembles KS histologically and it has been reported that immunohistochemistry in such lesions may be positive for smooth muscle actin and factor VIII related antigen, which are typically negative in KS. In both patients the lesions were positive for CD31, CD34, smooth muscle actin, and factor VIII related antigen, a profile typical of KS-like pyogenic granuloma. The lesions were tested for the presence of HHV-8 DNA, which to date has been consistently found in all types of KS. METHODS: The lesions were tested for the presence of HHV-8 DNA using the polymerase chain reaction (PCR). A known HHV-8 positive KS specimen was used as the positive control. Six samples of non-KS vascular skin lesions were used as negative controls for the PCR reaction. RESULTS: Both lesions were positive on PCR for HHV-8 and the specificity of product was confirmed by direct sequencing. None of the six control vascular skin lesions was positive for HHV-8. These results strongly indicate KS as the true diagnosis and are supported by the reported clinical course in both cases. CONCLUSIONS: Techniques targeting HHV-8 DNA for detection to confirm a diagnosis of KS are both sensitive and specific. In cases where the differential diagnosis includes KS-like pyogenic granuloma, caution should be taken not to diagnose solely on the basis of immunohistochemistry phenotype. In such cases, PCR targeting HHV-8 DNA sequences is a better diagnostic tool.

Aged↗

The role of electrostatic interactions in the regulation of the membrane association of G protein beta gamma heterodimers.

In this paper we report calculations of electrostatic interactions between the transducin (G(t)) betagamma heterodimer (G(t)betagamma) and phospholipid membranes. Although membrane association of G(t)betagamma is due primarily to the hydrophobic penetration into the membrane interior of a farnesyl chain attached to the gamma subunit, structural studies have revealed that there is a prominent patch of basic residues on the surface of the beta subunit surrounding the site of farnesylation that is exposed upon dissociation from the G(t)alpha subunit. Moreover, phosducin, which produces dissociation of G(t)betagamma from membranes, interacts directly with G(t)betagamma and introduces a cluster of acidic residues into this region. The calculations, which are based on the finite difference Poisson-Boltzmann method, account for a number of experimental observations and suggest that charged residues play a role in mediating protein-membrane interactions. Specifically, the calculations predict the following. 1) Favorable electrostatic interactions enhance the membrane partitioning due to the farnesyl group by an order of magnitude although G(t)betagamma has a large net negative charge (-12). 2) This electrostatic attraction positions G(t)betagamma so that residues implicated in mediating the interaction of G(t)betagamma with its membrane-bound effectors are close to the membrane surface. 3) The binding of phosducin to G(t)betagamma diminishes the membrane partitioning of G(t)betagamma by an order of magnitude. 4) Lowering the ionic strength of the solution converts the electrostatic attraction into a repulsion. Sequence analysis and homology model building suggest that our conclusions may be generalized to other Gbetagamma and phosducin isoforms as well.

Amino Acid Sequence↗

Imputation strategies for missing data in a school-based multi-centre study: the Pathways study.

Pathways is a multi-centre school-based trial sponsored by the National Heart, Lung, and Blood Institute testing the efficacy of an obesity prevention intervention in American Indian children. During the study's protocol development, we prepared an analysis plan that accounted for missing data. In this paper, we present a case study of the process we used to decide upon the final analysis plan. The primary endpoint of the Pathways study is a comparison of per cent body fat between treatment and usual care groups at the end of a three-year intervention. Other studies on children and Native Americans have had moderate to large amounts of missing data. As a result we were concerned that missing data in Pathways would affect the type I error rate and power of the test of our primary endpoint. We present results from our evaluation of three alternative procedures in this paper. The first is a multiple imputation procedure in which we replace missing values with resampled values from the observed data. The second is based on the Wilcoxon rank sum test; missing data in the intervention group receive the worst ranks. In the third, we use a multiple imputation procedure and replace missing values with predicted values from a regression equation with the coefficients estimated from observed follow-up data and baseline values. We found that the multiple imputation procedure that replaces missing values with predicted values had the best properties of the procedures we considered. The results from our simulation study showed that, for missing data patterns that are relevant to the Pathways study, this procedure has high power and maintains the type I error rate. Published in 2001 by John Wiley & Sons, Ltd.

Analysis of Variance↗

Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors.

Most traditional cytotoxic anticancer agents ablate the rapidly dividing epithelium of the hair follicle and induce alopecia (hair loss). Inhibition of cyclin-dependent kinase 2 (CDK2), a positive regulator of eukaryotic cell cycle progression, may represent a therapeutic strategy for prevention of chemotherapy-induced alopecia (CIA) by arresting the cell cycle and reducing the sensitivity of the epithelium to many cell cycle-active antitumor agents. Potent small-molecule inhibitors of CDK2 were developed using structure-based methods. Topical application of these compounds in a neonatal rat model of CIA reduced hair loss at the site of application in 33 to 50% of the animals. Thus, inhibition of CDK2 represents a potentially useful approach for the prevention of CIA in cancer patients.

Alopecia↗

Acetylcholinesterase treatment--modelling potential demand and auditing practice.

BACKGROUND: Acetylcholinesterase inhibitors represent an entirely novel treatment option for patients with Alzheimer's disease (AD). As such they represent a significant change in practice and a significant cost pressure on funding bodies. OBJECTIVES: To assess the impact of cholinesterase inhibitors on routine clinical practice. METHODS: We estimated potential demand for the compounds taking into account eligibility criteria and prescribing practice agreed between clinicians and funders. We then audited actual prescribing practice assessing whether the estimated demand matched actual demand and whether practice and prescribing criteria were adhered to. RESULTS: Over a two-year period we estimated the demand for treatment at a total of 89 patient years for the population of the audit unit. In practice only 24.5 patient years of therapy were received, the short fall apparently being due to low referral rates for treatment. Prescribing by clinicians matched practice guidelines and a high proportion of three monthly assessments using scales for cognition, function and global state were performed. Using these assessment procedures treatment successes could be differentiated from primary and secondary treatment failures and, where apparently appropriate, treatment could be stopped. CONCLUSION: In the real world of clinical practice demand for treatment in AD is modest but likely to grow and assessment with an aim to identifying those receiving benefit from treatment can be achieved.

Aged↗

Erdheim-chester disease.

Erdheim-Chester disease (ECD) is a rare histiocytic infiltrative disease, characterized by long bone sclerosis. We describe two confirmed cases of ECD, both of which demonstrate non-malignant retroperitoneal and peri-renal infiltration causing dilatation of the upper renal tracts. The cases are illustrated with contrast studies, computed tomography (CT) and magnetic resonance imaging (MRI). Typical sclerosis of the long bones was apparent on radiography. Both cases have been treated conservatively to date.A brief review of the literature regarding the manifestations of ECD is included. In cases of non-malignant retroperitoneal infiltration, ECD should be considered as a diagnosis and radiographs of the long bones performed.

Adult↗

Evidence for the validity of a patient-based instrument for assessment of outcome after revision hip replacement.

The Oxford hip score (OHS) is a patient-based instrument for assessment of outcome which is often used after total hip replacement, and the EuroQol 5D (EQ5D) is a patient-based generic questionnaire for health assessment. In an analysis of the outcome at one year of 609 revision hip replacements (RHRs), we compared the OHS and EQ5D scores, postoperative patient satisfaction and change in pain. About 25% of the operations were repeat RHRs. At one year, 57% of patients were very pleased with their operation. The correlation between preoperative and postoperative scores and change scores for the OHS and EQ5D was high. For both instruments the effect sizes were large, but the greater effect size of the OHS suggests that it is particularly sensitive to improvements after RHR. The effect scores of the OHS declined with the number of previous RHRs, while those for the EQ5D seemed less sensitive. Our results confirm the value of the OHS in assessing outcome after RHR.

Arthroplasty, Replacement, Hip↗

Biological factors influencing the RBE of neutrons: implications for their past, present and future use in radiotherapy.

The recent resurgence of interest in fast-neutron therapy, particularly for the treatment of prostate cancer, warrants a review of the original radiobiological basis for this modality and the evolution of these concepts that resulted from subsequent experimentation with the fast-neutron beams used for randomized clinical trials. It is clear from current radiobiological knowledge that some of the postulates that formed the mechanistic basis for past clinical trials were incorrect. Such discrepancies, along with the inherent physical disadvantages of neutron beams in terms of collimation and intensity modulation, may partially account for the lack of therapeutic benefit observed in many randomized clinical trials. Moreover, it is equally apparent that indiscriminate prescription of fast-neutron therapy is likely to lead to an adverse clinical outcome in a proportion of patients. Hence any renewed efforts to establish a niche for this modality in clinical radiation oncology will necessitate the development of a triage system that can discriminate those patients who might benefit from fast-neutron therapy from those who might be harmed by it. In the future, fast-neutron therapy might be prescribed based upon the relative status of appropriate molecular parameters that have a differential impact upon radiosensitivity to photons compared to fast neutrons.

Animals↗