Search PubMed⌕ Search

Biomedical subjects

P Price

Publications and source records attributed to P Price.

At least 19 recordsLinked to original sources
PubMed2007

The role of PET scanning in determining pharmacoselective doses in oncology drug development.

Molecular imaging is the most sensitive and specific method for measuring in vivo molecular pathways in man. Its use in oncology has developed significantly over the last 5-10 years. Molecules can be labelled with positron emitting isotopes and the emitted radiation is detected using sensitive positron emission tomography (PET) cameras. It is now possible to measure in vivo and normal tissue pharmacokinetics of anti-cancer drugs and investigate their mechanism of action. Radiolabelling of tracers can be used to measure specific pharmacodynamic endpoints and target identification. Increasing evidence shows how these technologies, when added to early drug development, can rapidly reduce the time for entry into man and early identification of mechanisms of action. With the move towards more segmented markets and identification of specific subgroups, PET's use for noninvasive biomarkers will become in- creasingly important. However, much international effort between academia and industry is required with prioritisation of development of this technology.

Animals↗
PubMed2006

Classification of functional recovery of anterior cruciate ligament copers, non-copers, and adapters.

OBJECTIVES: (a) To identify whether differences exist in the pattern of recovery with respect to functional outcomes for acutely ruptured anterior cruciate ligament deficient (ACLD) copers, adapters, and non-copers. (b) To identify clinically relevant outcomes that could distinguish between three functional subgroups. METHODS: A longitudinal study was used to measure gait variables and distance hop at regular intervals after injury using a digital camcorder and computer for quantitative analysis. A sample of 63 ACLD subjects entered the study; 42 subjects were measured at least three times. At 12-36 months after injury, subjects were classified as functional copers, adapters, or non-copers on the basis of which of their preinjury activities they had resumed. To determine the pattern of recovery, repeated measurements were analysed using a least squares fit of the data. RESULTS: 17% of ACLD subjects were classified as functional copers, 45% as adapters, and 38% as non-copers. Only 5% of those who participated in high demand activities before injury returned to them. ACLD copers had recovered above the control mean for all gait variables by 40 days after the injury. Hopping distance did not recover to the control mean. Non-copers struggled to recover to control limits and remained borderline for all the gait variables. CONCLUSIONS: Distinctive patterns of functional recovery for three subgroups of ACLD subjects have been identified. Gait variables and activity level before injury were the most useful variables for distinguishing between the subgroups. If potential for recovery is identified early after injury, then appropriate treatment can be given.

Adult↗
PubMed2006

Walking performance in people with diabetic neuropathy: benefits and threats.

AIMS/HYPOTHESIS: Walking is recommended as an adjunct therapy to diet and medication in diabetic patients, with the aim of improving physical fitness, glycaemic control and body weight reduction. Therefore we evaluated walking activity on the basis of capacity, performance and potential risk of plantar injury in the diabetic population before it can be prescribed safely. SUBJECTS, MATERIALS AND METHODS: Twenty-three subjects with diabetic neuropathy (DMPN) were compared with 23 patients with current diabetic foot ulcers, 16 patients with partial foot amputations and 22 patients with trans-tibial amputations. The capacity for walking was measured using a total heart beat index (THBI). Gait velocity and average daily strides were measured to assess the performance of walking, and its impact on weight-bearing was studied using maximum peak pressure. RESULTS: THBI increased (p<0.01) and gait velocity and daily stride count fell (p<0.001 for both) with progression of foot complications. The maximum peak pressures over the affected foot of patients with diabetic foot ulcers (p<0.05) and partial foot amputations (p<0.01) were higher than in the group with DMPN. On the contralateral side, the diabetic foot ulcer group showed higher maximum peak pressure over the total foot (p<0.05), and patients with partial foot amputations (p<0.01) and trans-tibial amputations (p<0.05) showed higher maximum peak pressure over the heel. CONCLUSIONS/INTERPRETATION: Walking capacity and performance decrease with progression of foot complications. Although walking is recommended to improve fitness, it cannot be prescribed in isolation, considering the increased risk of plantar injury. For essential walking we therefore recommend the use of protective footwear. Walking exercise should be supplemented by partial or non-weight-bearing exercises to improve physical fitness in diabetic populations.

Adult↗
PubMed2006

Cytomegalovirus (CMV)-specific CD8+ T cells in individuals with HIV infection: correlation with protection from CMV disease.

CD8+ cytotoxic T cells play a key role in immunological protection from clinical cytomegalovirus (CMV) disease. Numbers of CMV-specific CD8+ T cells are increased in untreated and antiretroviral-treated HIV patients compared with healthy controls. Accumulation of CMV-specific CD8+ T cells during HIV infection may reflect persistent reactivation of CMV owing to suboptimal immune control and/or oligoclonal expansion of the limited populations of CMV-specific CD8+ T cells present before antiretroviral therapy (ART). CD8+ T cells directed against the CMV immediate early (IE)-1 protein may play an important role in preventing CMV replication to pathogenic levels. However, immunological protection from CMV disease in HIV-infected individuals on ART does not appear to depend on total numbers of CMV-specific CD8+ T cells but rather on the presence of both effector-memory and effector CMV-specific CD8+ T cells that produce interferon-gamma and/or perforin in response to CMV antigens.

CD8-Positive T-Lymphocytes↗
PubMed2006

Radiotherapy treatment verification in the UK: an audit of practice in 2004.

AIMS: To audit current practice related to treatment verification undertaken in radiotherapy departments throughout the UK. MATERIALS AND METHODS: A questionnaire was circulated to the radiotherapy service managers of 62 radiotherapy centres in the UK. This looked in detail at the department demographics, imaging equipment, site-specific verification protocols, and training and competency assessment of staff responsible for verification. RESULTS: The response rate was 48% (30/62). All departments were using megavoltage imaging equipment in routine clinical practice. Twenty-four out of 29 (83%) departments that had electronic portal imaging capability were using image analysis software for verification. Twenty-nine out of 30 (97%) departments had site-specific written verification protocols. Twenty out of 30 (67%) treatment centres audited set-up errors within their department. Forty-three per cent of centres were using simulator image as the reference image of choice across all sites. Electronic portal imaging, alone or in combination with portal film, was being used for verification in 75% of the centres. Fifty-three per cent of centres used off-line correction strategies for measuring set-up errors across all sites. Radiographer-led interventions were primarily in the pelvis. CONCLUSION: Presently in the UK, verification strategies vary widely at individual treatment sites and between departments. Dedicated departmental verification teams, with input from radiographers, physicists and clinicians, may assist in the effective implementation of evidence-based verification. The inclusion of comprehensive verification protocols within multicentre radiotherapy trials encourages standardisation across treatment centres.

Humans↗
PubMed2006

Developments in and experience of kilovoltage X-ray cone beam image-guided radiotherapy.

This paper offers a realistic review of kilovoltage X-ray cone beam tomography integrated with the treatment machine for image-guided radiotherapy in the light of experience taking a commercial system from prototype development into clinical use. It shows that key practicalities cannot be ignored, in particular the regular characterization of mechanical flex during gantry rotation, the mapping of defects in flat panel image transducers and their response to X-ray exposure. The number of X-ray projections and the doses required for clinically useful cone beam reconstruction at different therapy sites are considered in the context of imaging that is fit for purpose. Three roles for cone beam tomography in radiotherapy are identified: patient setup in three dimensions (3D), where even low dose cone beam tissue detail is superior to megavoltage imaging; disease targeting where, despite wide field scatter and slow scanning, it is possible to generate images that are suitable for tumour delineation even at challenging sites; adaptive treatment planning, where calibrated cone beam images have been shown to provide sufficient target detail to support "plan of the day" selection and have the potential for planning with bulk corrections. With frequent use in mind, the need to limit patient dose during setup, yet maximize much needed image quality in the target zone, is considered. Finally, it is noted that the development of cone beam tomography for radiotherapy is far from complete, with X-ray source, image transducer, reconstruction algorithms and techniques for image profile collection still being researched.

Humans↗
PubMed2005

The assessment of antiangiogenic and antivascular therapies in early-stage clinical trials using magnetic resonance imaging: issues and recommendations.

Vascular and angiogenic processes provide an important target for novel cancer therapeutics. Dynamic contrast-enhanced magnetic resonance imaging is being used increasingly to noninvasively monitor the action of these therapeutics in early-stage clinical trials. This publication reports the outcome of a workshop that considered the methodology and design of magnetic resonance studies, recommending how this new tool might best be used.

Angiogenesis Inhibitors↗
PubMed2005

The development of functional imaging in the diagnosis, management and understanding of childhood brain tumours.

Imaging plays a fundamental role in the management of children with brain tumours. A series of new techniques, commonly grouped under the heading functional imaging, promise to give information on the properties and biological characteristics of tissues thereby adding to the structural information available from current imaging. The EPSRC funded a workshop to bring together clinicians from the UK Children's Cancer Study Group and scientific experts in the field to identify clinical problems in childhood brain tumours that may be addressed by functional imaging and to develop a clinical test bed for applying, evaluating and developing this new technology. The presentations and discussion sessions from the workshop are summarised and a review of the current 'state of the art' for this rapidly developing area provided. A key output of the workshop was agreement on a series of hypotheses which can be tested in carefully designed clinical studies.

Brain Neoplasms↗
PubMed2005

Does a central MHC gene in linkage disequilibrium with HLA-DRB1*0401 affect susceptibility to type 1 diabetes?

Subtypes of HLA-DR4 are associated with susceptibility or protection against type 1 diabetes (T1DM). We addressed whether this reflects linkage disequilibrium with the true susceptibility locus by studying broader MHC haplotypes marked by alleles of HLA-B, IKBL (adjacent to TNFA) and complement C4. The study used a largely Caucasian cohort from Western Australia. HLA-DRB1*0401 and HLA-DRB1*0405 marked susceptibility to T1DM. In Caucasians, DRB1*0401 occurs predominantly in the 44.1 ancestral haplotype (AH; HLA-A2,B44, DRB1*0401,DQB1*0301) and the 62.1AH (HLA-A2,B15(62),DRB1*0401,DQB1*0302). HLA-B15 marked susceptibility and HLA-B44 marked with resistance to T1DM in patients and controls preselected for HLA-DRB1*0401. A gene between TNFA and HLA-B on the 8.1AH (HLA-A1,B8,;DR3,DQ2) modifies the effects of the class II alleles. Here, alleles characteristic of the 62.1AH (C4B3, IKBL+446*T and HLA-A2,B15) were screened in donors preselected for HLA-DRB1*0401. C4B3 was associated with diabetes, consistent with a diabetes gene telomeric of MHC class II. However, increases in carriage of IKBL+446*T and HLA-A2,B15 were marginal, as too few control subjects were available with the diabetogenic alleles. However, with these tools, selection of HLA-DRB1*0401, DQB1*0302 donors who are positive and negative for C4B3 will allow bidirectional mapping of diabetes genes in the central MHC.

Adolescent↗
PubMed2005

Dysregulation of CD28 and CTLA-4 expression by CD4 T cells from previously immunodeficient HIV-infected patients with sustained virological responses to highly active antiretroviral therapy.

OBJECTIVES: Current guidelines recommend commencing highly active antiretroviral therapy (HAART) in HIV-infected patients when CD4 T-cell counts reach 350 cells/microL. However, late-presenting HIV-infected patients with CD4 T-cell counts<50 cells/microL are still common. The ability of long-term HAART to normalize immune dysregulation in severely immunodeficient HIV-infected patients remains unclear. Here we address indices of immune dysregulation in previously severely immunocompromised HIV-infected patients treated with long-term HAART who had achieved increased CD4 T-cell counts and complete suppression of HIV viraemia. METHODS: We examined expression of CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4) and intracellular perforin by CD4 and CD8 lymphocytes from 25 highly selected HIV-infected patients [nadir CD4 T-cell counts <50 cells/microL, >4 years on HAART and >6 months of complete viral suppression (<50 HIV-1 RNA copies/mL)] and 18 HIV-seronegative age- and sex-matched controls. RESULTS: HIV-infected patients had lower percentages of CD28-expressing CD4 lymphocytes and higher percentages of CTLA-4-expressing CD4 lymphocytes than controls. The percentage of CTLA-4-expressing CD4 lymphocytes correlated inversely with that of CD28-expressing CD4 lymphocytes. The proportion of CD4 lymphocytes expressing perforin was generally low. However, more HIV-infected patients than controls had >1% of CD4 lymphocytes expressing perforin [11 of 25 (44%) vs. one of 18 (5.5%)]. The percentage of CD8 lymphocytes expressing perforin did not differ between HIV-infected patients and controls. Amongst HIV-infected patients, the percentage of perforin-expressing CD8 lymphocytes correlated inversely with nadir but not current CD4 T-cell count. CONCLUSIONS: Expression of CD28, CTLA-4 and perforin by CD4 lymphocytes remain dysregulated in HIV-infected patients with previous severe immunodeficiency, despite increased CD4 T-cell counts and control of HIV viraemia by HAART.

Antigens, CD↗
PubMed2005

The effect of combination antiretroviral therapy on CD5 B- cells, B-cell activation and hypergammaglobulinaemia in HIV-1-infected patients.

OBJECTIVES: This study assessed B-cell activation, CD5 B-cells and circulating immunoglobulin levels in HIV-infected patients treated with combination antiretroviral therapy (CART). METHODS: Measurement of plasma immunoglobulin levels and electrophoresis of plasma proteins, and analyses of total numbers of B-cells and B-cells expressing CD 38 and CD5 in whole blood, were undertaken in 47 consecutive HIV-1-infected patients attending an out-patient clinic. RESULTS: All HIV-infected patients had similar percentages and numbers of B-cells. Proportions of CD5 B-cells in all HIV-infected patients were significantly lower than those in HIV-negative controls. Aviraemic HIV-infected patients on CART had lower percentages of CD5, CD 38 and CD5 CD 38 B-cell subsets and lower plasma levels of immunoglobulin G (IgG) and immunoglobulin A (IgA) than viraemic HIV-infected patients (untreated or on CART). However, 33-37% of aviraemic HIV-infected patients had IgG and IgA levels above the 95th percentile of the normal range defined in HIV-seronegative donors. In aviraemic HIV-infected patients, plasma IgA levels correlated only with proportions of activated (CD 38) B-cells. IgG levels did not correlate with the proportions of B-cell subsets or any marker of HIV disease activity. Monoclonal immunoglobulins were not detected in any plasma sample. CONCLUSIONS: Aviraemic HIV-infected patients on CART have lower plasma levels of IgG and IgA than viraemic HIV-infected patients, but levels are often above the normal range. CD5 B-cell numbers are depressed, so these cells are unlikely to contribute to hypergammaglobulinaemia in HIV-infected patients.

ADP-ribosyl Cyclase 1↗
PubMed2005

Measurement of functional recovery in individuals with acute anterior cruciate ligament rupture.

OBJECTIVES: To measure functional recovery following acute anterior cruciate ligament (ACL) rupture using a simple and reliable clinical movement analysis system. Clinic based methods that simultaneously quantify different aspects of movement over a range of activities and model functional recovery will help guide rehabilitation. METHODS: A longitudinal study was used to measure gait variables at initial physiotherapy attendance and then at monthly intervals using a digital camcorder and computer for quantitative analysis. Jogging and distance hopping were added during recovery. A sample of 63 ACL deficient subjects entered the study and 48 subjects were measured at least three times. To determine the pattern of recovery, repeated measurements were analysed using a least square fit of the data. RESULTS: Gait variables took between 95 and 130 days post injury to reach the control mean and stabilise shortly after this. Hopping distance for the injured leg took 62 days to recover to within normal limits and 5 months post injury to reach the control mean. Jogging was already within the control limits at 30 days post injury and demonstrated little change with recovery. CONCLUSIONS: Functional recovery of multiple variables has been modelled. In the early phase of post injury, gait velocity seems to be the most useful variable to measure improvement. Recovery of more challenging activities appears to take an average of 5 months. Therefore, patients may need to be monitored in physiotherapy until this time and advised not to return to sport until sufficient recovery is demonstrated on activities such as distance hopping.

Adult↗
PubMed2005

Modelling the expected increase in demand for particle radiotherapy: implications for the UK.

The present rapid worldwide expansion of particle radiotherapy services will inevitably have an impact on clinical practice within the UK. The most recent results of developmental trials using protons and carbon ions are impressive, with high cure rates and little or no functional normal tissue changes and a very low level of serious treatment-related morbidity. The potential numbers of patients that will demand or are referred for treatment abroad are estimated, assuming different rates of change and treatment capacities with time. Even if the maximum demand were to be under 10% of all patients presently treated by radiotherapy, significant numbers (amounting to several thousand patients per year) may be advised to seek treatment abroad between 5 and 10 years from now. The gap between overall demand and the estimated numbers could be partly, although substantially, filled by the establishment of a single large UK facility. Should demand increase beyond the estimated level, for example due to improved screening of cancer, then a network of UK particle radiotherapy centres will be required.

Humans↗
PubMed2005

An assessment of clinically optimal gold marker length and diameter for pelvic radiotherapy verification using an amorphous silicon flat panel electronic portal imaging device.

Verification of target organ position is essential for the accurate delivery of conformal radiotherapy. Megavoltage electronic portal imaging with flat panel amorphous silicon detectors delivers high quality images that can be used for verification of bony landmark position. Gold markers implanted into the target organ can be visualized and used as a surrogate of actual organ position. On-line compensation for marker displacement, by adjusting patient position, can reduce geometric errors associated with radiation delivery. This study assesses the optimal marker length and diameter to be used with an amorphous silicon (a-Si) flat panel detector and electronic portal images (EPIs), prior to implementation of a clinical programme of gold marker insertion in prostate cancer patients. Seven marker sizes varying from 3 mm to 8 mm in length and 0.8 mm to 1.1 mm in diameter were investigated in a group of patients undergoing pelvic radiotherapy using an 8 MV Elekta SL20 linear accelerator. Markers were placed on the skin entry and exit sites of the treatment beam and EPIs in both lateral and anterior pelvic views were acquired. Three observers independently assessed visibility success and failure using a subjective scoring system. Markers less than 5 mm in length or 0.9 mm in diameter were poorly visualized (<70% visualization success in lateral EPIs). The marker measuring 0.9 mm x 5 mm appears to be clinically optimal in pelvic radiotherapy patients (80% visualization success in lateral EPIs) and will be used for actual organ implantation.

Electronics, Medical↗
PubMed2005

Linguistic validation of the Cardiff Wound Impact Schedule into French, German and US English.

OBJECTIVE: Chronic leg wounds can represent a major health problem and have a negative emotional impact on patients' lives. The Cardiff Wound Impact Schedule (CWIS) was developed by the Wound Healing Research Unit at University of Wales College of Medicine to assess the quality of life in patients with chronic wounds. METHOD: To perform the linguistic validation (translation) of the CWIS into German, French and US English as a first step in making the questionnaire available globally. The standard linguistic validation process employed by the Mapi Research Institute was used to translate the CWIS into French and German. An adjusted process was used for the US English translation. RESULTS: The linguistic validation of the US English version was straightforward as it shares the same root language with the original UK version. The problems encountered in the French and German translations were mostly related to semantics and syntax. CONCLUSION: The CWIS is now available for further validation testing by the international community (the psychometric evaluation of each translated questionnaire). These translations will be useful to health-care providers undertaking formal quality-of-life assessments of patients with chronic leg wounds.

Activities of Daily Living↗
PubMed2004

Controversies in the radiotherapeutic management of poor prognosis locally advanced prostate cancer.

The Grand Round was held at the Christie Hospital, Manchester, U.K., on 30 November 2002. It followed a presentation by Dr David Dearnaley from the Royal Marsden Hospital in Sutton on 'Novel approaches and trials in prostate cancer'. Controversies in the management of locally advanced prostate cancer were illustrated by a case presentation and followed by a discussion on the evaluation of disease extent, and the roles of radiotherapy and hormone ablation.

Androgen Antagonists↗