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Biomedical subjects

C Doyle

Publications and source records attributed to C Doyle.

At least 19 recordsLinked to original sources
PubMed2005

Imaging findings and referral outcomes of rapid assessment stroke clinics.

AIM: A rapid assessment stroke clinic (RASC) was established to provide a rapid diagnostic service to individuals with suspected transient cerebral or ocular ischaemia or recovered non-hospitalized strokes. In this report we review imaging findings and clinical outcomes of patients proceeding to the carotid surgery programme. METHODS: Between October 2000 and December 2002, 1339 people attended the RASC. The findings of head CT and carotid Doppler ultrasound of the 1320 patients who underwent brain and carotid imaging were reviewed, and the number subsequently proceeding to carotid angiography and intervention was reported. RESULTS: CT head scans were normal in 57% of cases; 38% demonstrated ischaemia or infarction; and 3% yielded incidental or other significant findings not related to ischaemia. On screening with carotid Doppler ultrasound, 7.5% showed greater than 50% stenosis on the symptomatic side. A total of 83 patients (6.2%) proceeded to cerebral angiography and 65 (4.8%) underwent carotid endarterectomy or endovascular repair. CONCLUSION: Rapid-access neurovascular clinics are efficient in selecting patients for carotid intervention, but this is at a cost and the number of potential strokes prevented is small. Alternative management pathways based on immediate medical treatment need to be evaluated.

Adult↗
PubMed2004

In vivo surface wear mechanisms of femoral components of cemented total hip arthroplasties: the influence of wear mechanism on clinical outcome.

The appearance and mechanism of femoral stem wear was studied in 172 retrieved femoral components, of which 74 stems had been stable in vivo. Macroscopic, microscopic, and nano-level scales of examination were used. Loss of stem surface in response to micromotion (wear) was found to affect 93% of stems. However, changes were frequently difficult to see with the naked eye, and in 19% of cases they would have been missed completely without the use of light microscopy. The surface finish of the prosthesis determined the mechanism of stem wear. Matte surfaces showed typical abrasive processes that also damage the cement, releasing particulate debris from the cement and metal surfaces. This may destabilize the stem within the cement. Polished stems showed a typical fretting appearance with retention of debris on the stem surface and without significant damage to the cement. These differences in wear mechanism between matte and polished stems have significant effects on stem function.

Arthroplasty, Replacement, Hip↗
PubMed2003

Protein kinase C-epsilon promotes adipogenic commitment and is essential for terminal differentiation of 3T3-F442A preadipocytes.

The role of protein kinase C (PKC) isoforms in the commitment of multipotent fibroblasts to the adipocyte lineage and in their terminal differentiation into mature adipocytes was investigated. Ectopic overexpression of PKC-epsilon, but not other PKC isoforms, committed multipotent NIH-3T3 cells to adipogenic differentiation in the presence of hormonal inducers. In committed 3T3-F442A preadipocytes, PKC-epsilon protein expression increased during the course of terminal differentiation and cell-permeable PKC-epsilon inhibitory peptides, which prevent interaction with RACK (receptor for activated C-kinase) proteins, severely inhibited differentiation. PKC-epsilon accumulated in the nuclei of 3T3-F442A cells shortly after induction of differentiation and exhibited a distinctive punctate speckling immunocytochemical staining pattern. The spatiotemporal aspects of PKC-epsilon localization and expression coincided with that of C/EBP-beta, a transcription factor critically involved in promoting the early phase of adipogenesis. Collectively, these results demonstrate a role for PKC-epsilon in both adipogenic commitment and preadipocyte terminal differentiation.

3T3 Cells↗
PubMed2002

Alumina-alumina artificial hip joints. Part II: characterisation of the wear debris from in vitro hip joint simulations.

Until recently it was not possible to reproduce clinically relevant wear rates and wear patterns in in vitro hip joint simulators for alumina ceramic-on-ceramic hip prostheses. The introduction of microseparation of the prosthesis components into in vitro wear simulations produced clinically relevant wear rates and wear patterns for the first time. The aim of this study was to characterise the wear particles generated from standard simulator testing and microseparation simulator testing of hot isostatically pressed (HIPed) and non-HIPed alumina ceramic-on-ceramic hip prostheses, and compare these particles to those generated in vivo. Standard simulation conditions produced wear rates of approximately 0.1 mm3 per million cycles for both material types. No change in surface roughness was detected and very few wear features were observed. In contrast, when microseparation was introduced into the wear simulation, wear rates of between 1.24 (HIPed) and 1.74 mm3 per million cycles (non-HIPed) were produced. Surface roughness increased and a wear stripe often observed clinically on retrieved femoral heads was also reproduced. Under standard simulation conditions only nanometre-sized wear particles (2-27.5 nm) were observed by TEM, and it was thought likely that these particles resulted from relief polishing of the alumina ceramic. However, when microseparation of the prosthesis components was introduced into the simulation, a bi-modal distribution of particle sizes was observed. The nanometre-sized particles produced by relief polishing were present (1-35nm). however, larger micrometre-sized particles were also observed by both transmission electron microscopy (TEM) (0.021 microm) and scanning electron microscopy (SEM) (0.05-->10 microm). These larger particles were thought to originate from the wear stripe and were produced by trans-granular fracture of the alumina ceramic. In Part I of this study, alumina ceramic wear particles were isolated from the periprosthetic tissues from around Mittelmeier ceramic-on-ceramic hip prostheses. Characterisation of the particles by TEM and SEM revealed a bi-modal size distribution. SEM analysis revealed particles in the 0.05-3.2 microm size range. and TEM revealed particles in the 5-90 nm size range, indicating that microseparation of the prosthesis components may be a common event in vivo. This study (Part II) has revealed that the introduction of microseparation of the prosthesis components during the swing phase of the wear simulation reproduced clinically relevant wear rates, wear patterns and wear particles in in vitro hip joint simulators.

Aluminum Oxide↗
PubMed2002

Allo-immunization elicits CCR5 antibodies, SDF-1 chemokines, and CD8-suppressor factors that inhibit transmission of R5 and X4 HIV-1 in women.

Studies in humans suggest that allo-immunization induces CC-chemokines, CD8-suppressor factors (SF) and anti-HIV immunity. Here we report that allo-immunization with unmatched leucocytes from partners of women with recurrent spontaneous abortion elicits specific antibodies to the CCR5 receptor. Such antibodies inhibit replication of M-tropic HIV-1 (R5) and MIP-1beta-mediated chemotaxis. These CCR5 antibodies were also found in the sera of multiparous women that were naturally immunized by semi-allogeneic fetal antigens. The specificity of these antibodies was demonstrated by adsorption with CCR5 transfected HEK-293 cells, a baculovirus CCR5 preparation and a peptide of the 2nd extra-cellular loop of CCR5. Allo-immunization also stimulated increased concentrations of the CXC chemokine, SDF-1alpha and CD8-SF that inhibit T-tropic HIV-1 (X4) replication. We suggest that allo- immunization may elicit (a) CC chemokines, CCR5 antibodies and CD8-SF that inhibit M-tropic HIV-1 infection and (b) the CXC chemokine SDF-1alpha and CD8-SF that inhibit T-tropic HIV-1 infection.

Abortion, Habitual↗
PubMed2002

Development of gaze aversion as disengagement from visual information.

Older children, but not younger children, were found to look away more from the face of an interlocutor when answering difficult as opposed to easy questions. Similar results were found in earlier work with adults, who often avert their gaze during cognitively difficult tasks (A. M. Glenberg, J. L. Schroeder, & D. A. Robertson, 1998). Twenty-five 8-year-olds and 26 5-year-olds answered verbal reasoning and arithmetic questions of varying difficulty. The older children increased gaze aversion from the face of the adult questioner in response to both difficult verbal reasoning questions and difficult arithmetic questions. In contrast, younger children (5-year-olds) responded less consistently to cognitive difficulty. It is concluded that adultlike patterns of gaze aversion in response to cognitive difficulty are certainly acquired by 8 years of age. The implications of appropriate gaze aversion for children's management of cognitive processing resources are considered.

Child↗
PubMed2001

Immunogenicity of the extracellular domains of C-C chemokine receptor 5 and the in vitro effects on simian immunodeficiency virus or HIV infectivity.

The C-C chemokine receptor CCR5 serves an important function in chemotaxis of lymphocytes, monocytes, and dendritic cells. CCR5 is also the major coreceptor in most macrophage-tropic HIV-1 infections. Immunization of rhesus macaques with a baculovirus-generated CCR5 construct or peptides derived from the sequences of the four extracellular domains of CCR5 elicited IgG and IgA Abs, inhibition of SIV replication, and CD4+ T cell proliferative responses to three of the extracellular domains of CCR5. The immune sera reacted with cell surface CCR5 expressed on HEK 293 cells. T and B cell epitope mapping revealed major and minor T and B cell epitopes in the N-terminal, first, and second loops of CCR5. The three C-C chemokines, RANTES, macrophage-inflammatory protein-1alpha, and macrophage-inflammatory protein-1beta, were up-regulated by immunization with the CCR5-derived peptides, and the cell surface expression of CCR5 was decreased. The CCR5 Abs were complementary to the C-C chemokines in inhibiting HIV replication in vitro. Immunization with the four extracellular domains of CCR5 suggests that three of them are immunogenic, with maximal T cell responses being elicited by the second loop peptide. However, maximal Abs to the cell surface CCR5 or viral inhibitory Abs in vitro were induced by the N-terminal peptide. Up-regulation of the three C-C chemokines and down-modulation of cell surface CCR5 were elicited by the second loop, N-terminal, and first loop peptides. The data suggest that a dual mechanism of C-C chemokines and specific Abs may engage and down-modulate the CCR5 coreceptors and prevent in vitro HIV or SIV replication.

Amino Acid Sequence↗
PubMed2001

Does palliative chemotherapy palliate? Evaluation of expectations, outcomes, and costs in women receiving chemotherapy for advanced ovarian cancer.

PURPOSE: The value of palliative chemotherapy in women with refractory and recurrent ovarian cancer is difficult to quantify, and little is known about patient expectations from these treatments. We evaluated in the current prospective study patient expectations, palliative outcomes of chemotherapy, and the inherent resource utilization in patients undergoing second- or third-line chemotherapy for recurrent or refractory advanced ovarian cancer. METHODS: The European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire C30 (EORTC QLQ C30) and Functional Assessment of Cancer Therapy-Ovarian (FACT-O) questionnaires were used to assess palliative benefit and an in-house questionnaire was used to gauge patient expectations. The minimal clinically important difference (MCID) was calculated by asking women to make a global rating of change and correlating this to the EORTC QLQ C30. Resource use was recorded and costs were calculated. RESULTS: Twenty-seven patients were accrued. Objective response was documented on seven of 27. The median survival was 11 months. Sixty-five percent of women expected that chemotherapy would make them live longer and 42% that it would cure them. After two cycles, quality-of-life (QL) improvement was seen particularly in global function (11 of 21) and emotional function (13 of 21) with EORTC QLQ C-30. Improvement was sustained for a median of 2 and 3 months, respectively, in these categories. The MCID was calculated to be 0.39 on a seven-point scale for physical function and 0.13 for global function. The mean total cost per patient for the study period was Can $12,500. CONCLUSION: Patient expectations from these treatments are often unrealistic. Although objective responses are low, active palliation with chemotherapy is associated with substantive improvement in patients' emotional function and global QL, with overall costs that seem relatively modest.

Adult↗
PubMed2001

In vitro dissolution behaviour of two morphologically different thermally sprayed hydroxyapatite coatings.

Two types of hydroxyapatite coating on titanium substrates were produced by vacuum plasma spraying and detonation gun spraying. The response of the coatings to immersion in Ringer's solution at pH 7.2 and held at 37 degrees C for periods of one, two, four and eight weeks was compared. X-ray diffraction was used to measure changes in crystallinity and residual stresses. Porosity and coating thickness were measured using optical microscopy combined with image analysis. Surface morphology was characterised using scanning electron microscopy and Talysurf measurements. The DGUN coatings were found initially to have a lower crystallinity and porosity but higher surface roughness and residual stress level than the VPS coatings. This resulted in a higher rate of dissolution compared to the more stable VPS coatings.

Biocompatible Materials↗
PubMed2001

In vitro fatigue behaviour of vacuum plasma and detonation gun sprayed hydroxyapatite coatings.

The fatigue behaviour of vacuum plasma sprayed (VPS) and detonation gun sprayed (DGUN) hydroxyapatite coatings on titanium substrates has been compared in air and in buffered Ringer's solution. There was an increase in the surface microcracking and bulk porosity of both types of coating tested in air. After 1 million cycles in Ringer's solution the VPS coatings had completely delaminated from their substrates. In contrast the DGUN coatings retained their integrity when tested up to 10 million cycles but were beginning to show signs of delamination at the interface.

Durapatite↗
PubMed2001

Wear of HIPed and non-HIPed alumina-alumina hip joints under standard and severe simulator testing conditions.

Wear and the biological response to wear debris of artificial joints remain major concerns in total hip arthroplasty (THA). The long-term effects of UHMWPE wear debris are well documented and these have led to interest in alternate bearing materials for THA. Alumina ceramic-ceramic hip joints have been successfully used for more than 30 years with low wear and little incidence of osteolysis. The most common wear pattern observed on retrieved components is an elliptical wear 'stripe' on the heads and a corresponding worn area on the cup with an approximated wear rate of 1-5 mm3 pa. More severe wear has also occasionally occurred, usually in association with an abnormal clinical history. Modern alumina-alumina THAs use an improved HIPed (hot isostatically pressed) alumina ceramic-bearing material which may be more resistant to severe wear. Previous in vitro simulator studies have not replicated in vivo wear rates or mechanisms. The aim of this study was to compare previous generation non-HIPed alumina and modern HIPed alumina in a hip joint simulator under 'normal' and 'harsh' testing conditions. HIPed alumina was found to have a lower wear rate than non-HIPed alumina, although the difference was not statistically significant at the 95% confidence level. Testing in Gelofusine and water lubricants did not elevate the wear rates of either material. Elevated swing phase load testing also had no significant effect on the wear rates of either material. Testing in the absence of any lubricant produced very severe wear of the non-HIPed material in one specimen only.

Aluminum Oxide↗
PubMed2001

The long-term safety and efficacy of pramipexole in advanced Parkinson's disease.

Objective: To assess the long-term safety and efficacy of pramipexole in advanced Parkinson's disease over a four year time period.Methods: This study is an open-label extension trial of pramipexole for Parkinson's disease open to patients completing a double-blind placebo controlled safety and efficacy trial of this drug. Three hundred and six patients entered the trial. These patients had moderate to severe PD (stage II-IV Hoehn and Yahr during off time) and were experiencing motor fluctuations. Patients were titrated over a six week period and then entered a maintenance phase which lasted up to 50 months. Patients were evaluated every 3 months using the Unified Parkinson's Disease Rating Scale (UPDRS II, III and IV) and modified Schwab and England scale (S/E).Results: Sixty-four percent (197) of the 306 patients who entered this study completed it. Patients showed steady improvement over the 6 week ascending dose interval when pramipexole was reintroduced into the trial as the open-label study medication. Over the duration of the trial patients slowly returned to their baseline levels. This was true for all measures evaluated except for the UPDRS part IV. On UPDRS part IV patients remained below their baseline score which indicated an improvement for the duration of the study. Patterns similar to the overall scores were seen when the individual components of the UPDRS scale part II for "on" and "off" periods and part III were evaluated. However tremor during "on" periods showed improvement over baseline for the duration of the trial. The most common adverse events secondary to pramipexole occurring in greater than 10% of patients included dyskinesias, asymptomatic orthostatic hypotension, dizziness, insomnia, and hallucinations.Conclusion: Pramipexole was well tolerated for up to 4 years. Pramipexole treatment appeared to show continued efficacy in the treatment of Parkinson's disease for 3 years in this open-label descriptive study. After 3 years there was a gradual return to baseline motor states perhaps suggesting progression of Parkinson's disease.

Journal Article↗
PubMed2001

The influence of acetabular cup angle on the wear of "BIOLOX Forte" alumina ceramic bearing couples in a hip joint simulator.

The wear of "Biolox Forte" alumina ceramic bearing couples has been investigated at two different acetabular cup angles in a physiological hip joint simulator. All cups were set in the anatomical position of 45 degrees inclination in the M/L plane for the first two million cycles and then four of the six cups were re-aligned to 60 degrees for a further three million cycles. A "running-in" wear of 0.14 mm3 per million cycles was observed for the first million cycles, after which a steady state wear rate of 0.05 mm3 per million cycles was observed. Increasing the acetabular cup angle to 60 degrees did not significantly affect the wear rate.

Journal Article↗
PubMed2001

The effect of molecular orientation and acetylene-enhanced crosslinking on the wear of UHMWPE in total artificial joints.

This paper investigates the benefits of combining roll-drawing and acetylene-enhanced crosslinking to alter the mechanical properties of the ultra high molecular weight polyethylene (UHMWPE) used in total hip and knee replacements, with the aim of improving its resistance to wear. UHMWPE was processed via crosslinking, roll-drawing and a combination of crosslinking and roll-drawing and subjected to gel content analysis, tensile tests, X-ray diffraction and wear tests using different types of motion and smooth and rough counterfaces. Purely roll-drawn materials with length and width draw ratios of lambda l x lambda w = 1.3 x 1.0 and lambda1 x lambdaw = 1.6 x 0.9 respectively, were found to have lower wear factors in a unidirectional motion test with a rough counterface when compared to the virgin material. The crosslinked roll-drawn material, with length and width draw ratios of lambda1 x lambdaw = 1.6 x 0.9, was seen to possess five crosslinks per initial number average molecule. This crosslinked and roll-drawn material showed 5.5 times less wear than the virgin material in a multidirectional motion test with a smooth counterface and 1.4 times more wear than the virgin material in a unidirectional motion test with a rough counterface. Hence this study supports previous work by the authors that acetylene-enhanced crosslinked materials may show benefits for a total hip replacement, but only where the femoral head remains smooth. The improvements in wear with the roll-drawn material in unidirectional tests were smaller, but may prove to have some benefits in the knee.

Journal Article↗