PubMed Health⌕ Search

Biomedical subjects

Paul Roberts

Publications and source records attributed to Paul Roberts.

14 recordsLinked to original sources
PubMed2006

Effect of bearing geometry and structure support on transient elastohydrodynamic lubrication of metal-on-metal hip implants.

An effective lubrication can significantly reduce wear of metal-on-metal artificial hip joints. The improvement of the lubrication can be achieved through the optimisation of the bearing geometry in terms of a small clearance and/or the structural support such as a polyethylene backing underneath a metallic bearing in a sandwich acetabular cup form. The separate effects of these two factors on fluid film lubrication of 28 mm diameter metal-on-metal total hip joints under walking conditions were numerically investigated in this paper. The results show that a larger lubricant film due to the polyethylene backing can be significantly enhanced by the transient squeeze-film action, particularly during the stance phase, and a similar lubricant film can be developed for both the monolithic cup relying on the smaller clearance and the sandwich cup benefiting from the polyethylene backing. Both cup systems can function in a wide range of lubrication regimes, covering both mixed and fluid film, under the current design and manufacture conditions.

Computer Simulation↗
PubMed2005

Mechanisms of benzarone and benzbromarone-induced hepatic toxicity.

Treatment with benzarone or benzbromarone can be associated with hepatic injury. Both drugs share structural similarities with amiodarone, a well-known mitochondrial toxin. Therefore, we investigated the hepatotoxicity of benzarone and benzbromarone as well as the analogues benzofuran and 2-butylbenzofuran. In isolated rat hepatocytes, amiodarone, benzarone, and benzbromarone (20 micromol/L) decreased mitochondrial membrane potential by 23%, 54% or 81%, respectively. Benzofuran and 2-butylbenzofuran had no effect up to 100 micromol/L. In isolated rat liver mitochondria, amiodarone, benzarone, and benzbromarone, but not benzofuran, decreased state 3 oxidation and respiratory control ratios for L-glutamate (50% decrease of respiratory control ratio at [micromol/L]: amiodarone, 12.9; benzarone, 10.8; benzbromarone, <1). Amiodarone, benzarone, and benzbromarone, but not benzofuran, also uncoupled oxidative phosphorylation. Mitochondrial beta-oxidation was decreased by 71%, 87%, and 58% with 100 micromol/L amiodarone or benzarone and 50 micromol/L benzbromarone, respectively, but was unaffected by benzofuran, whereas ketogenesis was not affected. 2-Butylbenzofuran weakly inhibited state 3 oxidation and beta-oxidation only at 100 micromol/L. In the presence of 100 micromol/L amiodarone, benzarone or benzbromarone, reactive oxygen species production was increased, mitochondrial leakage of cytochrome c was induced in HepG2 cells, and permeability transition was induced in isolated rat liver mitochondria. At the same concentrations, amiodarone, benzarone, and benzbromarone induced apoptosis and necrosis of isolated rat hepatocytes. In conclusion, hepatotoxicity associated with amiodarone, benzarone, and benzbromarone can at least in part be explained by their mitochondrial toxicity and the subsequent induction of apoptosis and necrosis. Side chains attached to the furan moiety are necessary for rendering benzofuran hepatotoxic.

Amiodarone↗
PubMed2005

Ginkgo biloba: persistent bleeding after total hip arthroplasty caused by herbal self-medication.

We describe a case of persistent postoperative bleeding following total hip arthroplasty in which, initially, no obvious cause was identified. The patient was taking ginkgo biloba extract, an unlicensed herbal medicine taken to improve mental alertness. Ginkgo biloba is an anticoagulant that inhibits platelet-activating factor and is contraindicated with aspirin. Four weeks' postoperatively, the ginkgo was stopped, and the bleeding stopped 6 weeks later.

Aged↗
PubMed2005

The evolution of hip resurfacing arthroplasty.

Metal-on-metal hip resurfacing, a significant recent development in hip arthroplasty, preserves proximal femoral bone stock, optimizes stress transfer to the proximal femur, and offers inherent stability and optimal range of movement. The results of hip resurfacing in the 1970s and 1980s were disappointing, and the procedure was largely abandoned by the mid-1980s. The renaissance of metal-on-metal articulations for total hip arthroplasty has enabled the introduction of new hip resurfacings, and many implant manufacturers have introduced such systems. Early results are encouraging, and complications commonly seen in the 1970s and 1980s, such as early implant loosening and femoral neck fracture, are rare. Background research and better understanding of implant failure suggest that current hip resurfacing technology has developed beyond that of an experimental procedure.

Arthroplasty, Replacement, Hip↗
PubMed2005

Influence of the clearance on in-vitro tribology of large diameter metal-on-metal articulations pertaining to resurfacing hip implants.

Large-diameter metal-on-metal articulations may provide an opportunity for wear reduction in total hip implants because earlier studies have shown that the formation of a fluid film that completely separates the bearing surfaces is theoretically possible. In such a lubrication mode and under ideal conditions, there is theoretically no amount of wear. Studies have suggested that the two primary parameters controlling the lubrication mode are the diameter and the clearance of the articulation. The goal of the present study was to experimentally investigate the influence of these two parameters on the wear behavior of large-diameter metal-on-metal articulations pertaining to resurfacing hip implants. The results of this in vitro investigation showed that longer running-in periods and higher amounts of running-in wear were associated with larger clearances.

Biomechanical Phenomena↗
PubMed2005

The incidence and prevalence of type-1 diabetes mellitus.

AIM: To determine the incidence, prevalence of type-1 diabetes mellitus (DM) and the presence of islet-cell antibodies (ICAs) in people of African ancestry in the Bahamas. METHOD: Hospital records of type-1 DM were reviewed. Seventeen consecutive patients had postmeal C-peptide and ICA determined. RESULTS: The incidence and prevalence of type-1 DM in the Bahamas were: incidence--10.1/100,000, age 0-14 years; and prevalence--31/100,000 age 0-24 years. Only two out of 17 (11.8%) patients had ICAs. CONCLUSION: Type-1 DM is common in children of African ancestry in the Bahamas. ICAs were absent in the majority of the patients.

Adolescent↗
PubMed2003

FUS/ERG gene fusions in Ewing's tumors.

Ewing's tumors are rare pediatric neoplasms that are characterized by specific chromosomal translocations and gene rearrangements. All of the fusion genes reported to date in Ewing's tumors juxtapose the EWS gene at 22q12 to an ETS-related gene, the most common of which are FLI1 at 11q24 and ERG at 21q22. We present here four cases of Ewing's tumor, which showed no evidence of a EWS gene rearrangement, but instead contained translocations involving 16p11 and 21q22. A rearrangement involving the same chromosome bands, t(16;21)(p11;q22), is found in rare cases of acute myeloid leukemia and fuses the FUS gene at 16p11 to the ERG gene at 21q22. In two of our Ewing's tumor cases, we were able to show at the sequence level that the translocation between chromosomes 16 and 21 similarly results in a FUS/ERG fusion. In one case, exons 1-5 and most of exon 6 of FUS were fused in-frame to exon 9 of ERG; in the other case, FUS exons 1-7 were fused in-frame to ERG exons 8-9. The functional fusion transcript is expected to be expressed from the der(21)t(16;21) derivative. In the two other t(16;21)-positive Ewing's cases, we performed bacterial artificial chromosome fluorescence in situ hybridization analysis on metaphases and interphase nuclei to demonstrate colocalization of bacterial artificial chromosomes containing FUS and ERG genes, also highly suggestive of fusion gene formation. These represent the first four cases where FUS, rather than EWS, is rearranged with an ETS-family transcription factor in Ewing's tumors. Our data provide additional evidence that the transactivation domains of the TET family of RNA-binding proteins (such as EWS and FUS) are interchangeable, and suggests a novel mechanism of oncogenesis in Ewing's tumors.

Adolescent↗
PubMed2003

Detection by fluorescence in situ hybridization of microdeletions at 1p36 in lymphomas, unidentified on cytogenetic analysis.

The chromosomal band 1p36 exhibits frequent loss of heterozygosity in a variety of human malignancies, suggesting the presence of an as yet unidentified tumor suppressor gene. The faint terminal subbands often make cytogenetic analysis of 1p36 particularly difficult. Small deletions at this locus may therefore escape detection on analysis by conventional cytogenetics, a hypothesis that we have explored using fluorescence in situ hybridization (FISH) in malignant lymphoma. The study cohort consisted of 20 cases of lymphoma of various subtypes without any 1p abnormality on G-banded karyotyping. FISH was performed using a human chromosome 1 paint and a bacterial artificial chromosome probe RP4-755G5 localizing to 1p36.33, the most telomeric subband of 1p36. Tumors demonstrating 1p36.33 deletions were additionally analyzed by FISH using a second probe from the proximal 1p36.1 subband, to further define the breakpoint. Eight cases of follicular lymphoma (FL), 5 diffuse large B-cell lymphomas (DLBCL), 2 Hodgkin disease, 2 B-cell small lymphocytic lymphomas, 2 T-cell lymphomas, and 1 marginal zone lymphoma were analyzed. FISH identified deletions at 1p36.33 in 5 of the 20 cases: 3 DLBCL and 2 FL. FISH is considerably more sensitive for identifying lymphoma genetic alterations than conventional cytogenetics. Deletion of the distal part of the 1p36 may be a much more common aberration than previously recognized in lymphoma.

Adolescent↗
PubMed2003

"Double" potentials define linear lesion conduction block using a novel mapping/linear lesion ablation catheter.

INTRODUCTION: A novel mapping/ablation catheter using a coaxially ablation electrode (E) that is moveable between distal and proximal ring electrodes along its shaft was used to create a linear lesion over the cavotricuspid isthmus (CTI) and bidirectional block in 32 patients (21 men; age 38-79 years) undergoing ablation for counterclockwise atrial flutter. METHODS AND RESULTS: Two bipolar electrograms (E1 and E2) were recorded: between E and the distal ring electrode and between E and the proximal ring electrode. Interpole distance varied for both as the E traversed the slide shaft. Given the catheter's concept, these bipoles are orientated exactly along the line of lesion creation. Prior to ablation, unitary bipolar electrograms were recorded along the catheter slide shaft position. As the CTI lesion was created (E moved along the catheter slide shaft in 2-mm steps with radiofrequency energy delivered to achieve 65 degrees C for 60 sec at each), double potentials (DP) were observed. Interpotential distance became maximal with completion of the linear lesion and bidirectional block. DPs were noted in all these procedures. With pacing from the low septal right atrium at bidirectional block creation, interpotential timing was 140.9 +/- 15 msec and from the low right atrial free wall was 145.13 +/- 18 msec. In sinus rhythm, DP interpotential timing was less (35.13 +/- 9 msec) as activation fronts arrived from both septal and anterior atrial aspects. CONCLUSION: Bipolar recordings from the coaxially moveable electrode catheter provide unique electrogram data. DPs recorded during and after linear lesion creation can define conduction block across that lesion without the need for additional mapping catheters or complex mapping technology.

Adult↗
PubMed2003

Piecemeal microautophagy of nucleus in Saccharomyces cerevisiae.

Nucleus-vacuole (NV) junctions in Saccharomyces cerevisiae are formed through specific interactions between Vac8p on the vacuole membrane and Nvj1p in the nuclear envelope. Herein, we report that NV junctions in yeast promote piecemeal microautophagy of the nucleus (PMN). During PMN, teardrop-like blebs are pinched from the nucleus, released into the vacuole lumen, and degraded by soluble hydrolases. PMN occurs in rapidly dividing cells but is induced to higher levels by carbon and nitrogen starvation and is under the control of the Tor kinase nutrient-sensing pathway. Confocal and biochemical assays demonstrate that Nvj1p is degraded in a PMN-dependent manner. PMN occurs normally in apg7-delta cells and is, therefore, not dependent on macroautophagy. Transmission electron microscopy reveals that portions of the granular nucleolus are often sequestered into PMN structures. These results introduce a novel mode of selective microautophagy that targets nonessential components of the yeast nucleus for degradation and recycling in the vacuole.

Autophagy-Related Protein 7↗
PubMed2002

Cytogenetic abnormalities and clinical outcome in Wilms tumor: a study by the U.K. cancer cytogenetics group and the U.K. Children's Cancer Study Group.

BACKGROUND: Tumor genetic features reported to correlate with adverse outcome in Wilms tumor include karyotype complexity, losses of material from the short arm of chromosome 1 and from the long arms of chromosomes 11, 16 and 22 and gain of material from the long arm of chromosome 1. This study sought to test these associations in a large series of tumors studied by cytogenetic analysis. Identification of markers associated with elevated risk of relapse and fatal outcome could allow more effective treatment stratification at presentation. PROCEDURE: Thirteen member laboratories of the U.K. Cancer Cytogenetics Group provided results from a 12-year period. Karyotype abnormalities were correlated with clinical data (age, tumor stage, and histology) and outcome data provided by the central register of the U.K. Children's Cancer Study Group. RESULTS: Of 127 abnormal karyotypes, 78 included a reputedly "poor prognosis" feature. Univariate survival analysis showed no significant adverse effect for karyotype complexity, 1p loss or 11q loss. The poor outcome of cases with 16q loss was of borderline significance, but this effect was restricted to those tumors with unbalanced translocation der(16)t(1q;16q). The association between relapse risk and gain of 1q material was not significant. Only monosomy 22 was a significant marker of poor outcome in univariate analysis (13 cases showing 50% relapse free survival at 5 years compared to 79% survival for the remaining 114 cases, P = 0.02). In multivariate analysis, significant independent predictors of poor outcome were 1q gain (Hazard Ratio 3.4), stage IV disease (HR 5.0), and monosomy 22 (HR 5.9). CONCLUSIONS: Loss of chromosome 22 identifies high risk Wilms tumors. The prognostic significance of 1q gain, 16q loss and unbalanced translocation der(16)t(1q;16q) is unresolved and warrants further investigation.

Adolescent↗