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Biomedical subjects

C Walker

Publications and source records attributed to C Walker.

At least 19 recordsLinked to original sources
PubMed2007

Paediatric eczema and psychosocial morbidity: how does eczema interact with parents' illness beliefs?

BACKGROUND: Thus far there has been relatively little work on children's illness representations regarding eczema and how these relate to parental conceptualizations of their child's psychosocial health. This is important because the challenge of raising a child with a serious illness can affect many facets of a parent's everyday life and the behaviour of parents can be closely related to the health of the child. METHODS: Two hundred and thirty-two children with eczema, asthma, eczema and asthma, and healthy controls between 7 and 12 years of age and their parents were recruited. Children were administered the Children's Illness Perception Questionnaire. Questionnaires completed by the parents were The Personality Inventory for Children and The Parental Stress Inventory. RESULTS: Parents of children with eczema did not judge their children to have poorer psychosocial health than controls, but parents of children with eczema could not be distinguished between in terms of whether their child was significantly affected by their eczema or not. CONCLUSIONS: This work could have important implications for the quality of life of the child and for the parent-child relationship and these implications are considered.

Case-Control Studies↗
PubMed2006

Genetic and metabolic predictors of chemosensitivity in oligodendroglial neoplasms.

The -1p/-19q genotype predicts chemosensitivity in oligodendroglial neoplasms, but some with intact 1p/19q also respond and not all with 1p/19q loss derive durable benefit from chemotherapy. We have evaluated the predictive and prognostic significance of pretherapy (201)Tl and (18)F-FDG SPECT and genotype in 38 primary and 10 recurrent oligodendroglial neoplasms following PCV chemotherapy. 1p/19q loss was seen in 8/15 OII, 6/15 OAII, 7/7 OIII, 3/11 OAIII and was associated with response (Fisher-Exact: P=0.000) and prolonged progression-free (log-rank: P=0.002) and overall survival (OS) (log-rank: P=0.0048). Response was unrelated to metabolism, with tumours with high or low metabolism showing response. Increased (18)F-FDG or (201)Tl uptake predicted shorter progression-free survival (PFS) in the series (log-rank: (201)Tl P=0.0097, (18)F-FDG P=0.0170) and in cases with or without the -1p/-19q genotype. Elevated metabolism was associated with shorter OS in cases with intact 1p/19q (log-rank: (18)F-FDG P=0.0077; (201)Tl P=0.0004) and shorter PFS in responders (log-rank: (18)F-FDG P=0.005; (201)Tl P=0.0132). (201)Tl uptake and 1p/19q loss were independent predictors of survival in multivariate analysis. In this initial study, (201)Tl and (18)F-FDG uptake did not predict response to PCV, but may be associated with poor survival following therapy irrespective of genotype. This may be clinically useful warranting further study.

Adult↗
PubMed2006

Clinical use of genotype to predict chemosensitivity in oligodendroglial tumors.

BACKGROUND: The -1p/-19q genotype has been associated with prolonged survival and chemosensitivity in oligodendroglial neoplasms, but the predictive and prognostic significance of genotype in the routine clinic is not established. METHODS: The authors investigated allelic imbalance in 1p36, 19q13, 17p13, 10p12-15, and 10q22-26 and p53 mutation in a cohort representative of clinical practice at their center (50 primary, 26 recurrent cases) given PCV chemotherapy between 2000 and 2003 and compared with response and outcome following PCV. RESULTS: 1p/19q loss was found in 12/19 OII, 10/23 OAII, 11/13 OIII, and 6/21 OAIII. Response, seen in 92% with 1p/19q loss, was associated with the -1p/-19q genotype (Fisher exact: p < 0.001) regardless of WHO grade or whether primary or recurrent. 1p/19q loss was an independent prognostic factor associated with longer progression-free (PFS) and overall survival (OS) (Cox regression: PFS and OS p < 0.001), with greater impact on PFS than OS in primary tumors, and OS at recurrence. 17p13 loss and p53 mutation were associated with poor prognosis in recurrent tumors and chromosome 10 loss was associated with short PFS and OS in primary tumors. Histologic subtype did not influence outcome in tumors of equivalent genotype. Genotype had greater association with response and outcome than conventional clinical factors. A total of 29% with intact 1p/19q and a variety of genetic or clinicopathologic characteristics responded in association with increased PFS and OS. CONCLUSIONS: The -1p/-19q genotype predicted response and favorable outcome following PCV chemotherapy corroborating genetic analysis to guide routine clinical management. However, some cases with intact 1p/19q also had clinical benefit.

Adult↗
PubMed2006

Expression of ADAMTS-8, a secreted protease with antiangiogenic properties, is downregulated in brain tumours.

Angiogenesis and extracellular matrix degradation are key events in tumour progression, and factors regulating stromal-epithelial interactions and matrix composition are potential targets for the development of novel anti-invasive/antiangiogenic therapies. Here, we examine the expression of ADAMTS-8, a secreted protease with antiangiogenic properties, in brain tissues. Using quantitative RT-polymerase chain reaction (PCR), high, equivalent expression of ADAMTS-8 was found in normal whole brain, cerebral cortex, frontal lobe, cerebellum and meninges. ADAMTS-8 expression in 34 brain tumours (including 22 high-grade gliomas) and four glioma cell lines indicated at least two-fold reduction in mRNA compared to normal whole brain in all neoplastic tissues, and no detectable expression in 14 out of 34 (41%) tumours or four out of four (100%) cell lines. In contrast, differential expression of TSP1 and VEGF was seen in nine out of 15 (60%) and seven out of 13 (54%) tumours, with no relationship in the expression of these genes. Immunohistochemistry and Western analysis indicated downregulation of ADAMTS-8 protein in >77% tumours. Methylation-specific PCR analysis of ADAMTS-8 indicated promoter hypermethylation in one out of 24 brain tumours (a metastasis) and three out of four glioma cell lines suggesting an alternative mechanism of downregulation. These data suggest a role for ADAMTS-8 in brain tumorigenesis, warranting further investigation into its role in regulation of tumour angiogenesis and local invasion.

ADAM Proteins↗
PubMed2006

The effect of exposure to irrigant solutions on apical dentin biofilms in vitro.

This study assessed the effectiveness of different concentrations of sodium hypochlorite (NaOCl), 2% chlorhexidine (CHX) (Vista Dental Products, Racine, WI), and BioPure MTAD (Dentsply Endodontics-Tulsa Dental, Tulsa, OK). Intracanal contents were collected from 10 patients diagnosed with chronic apical periodontitis. The samples were cultured on hemisections of root apices to generate a polymicrobial biofilm. Each biofilm was separately immersed in 6% NaOCl, 3% NaOCl, 1% NaOCl, 2% CHX, 1% NaOCl followed by BioPure MTAD, and sterile phosphate buffered solution (PBS). SEM analysis showed 6% NaOCl and 3% NaOCl were capable of disrupting and removing the biofilm; 1% NaOCl and 1% NaOCl followed by MTAD were capable of disrupting the biofilm, but not eliminating bacteria; 2% CHX was not capable of disrupting the biofilm. Viable bacteria could not be cultured from specimens exposed to 6% NaOCl, 2 % CHX, or 1% NaOCl followed by BioPure MTAD. These results indicate that 6% NaOCl was the only irrigant capable of both rendering bacteria nonviable and physically removing the biofilm.

Biofilms↗
PubMed2006

The importance of children's illness beliefs: the Children's Illness Perception Questionnaire (CIPQ) as a reliable assessment tool for eczema and asthma.

A lack of information about disease in children can lead to erroneous views such as children believing that hospital admittance or the presence of a disease is a punishment for a perceived wrong. There has thus far been no standard tool available to measure children's illness conceptualizations from a Leventhalian framework. Three groups of children with eczema, asthma and eczema and asthma between the ages of 7 and 12 years of age were recruited. Children were given the Children's Illness Perception Questionnaire (CIPQ), a 26-item instrument adapted from the Illness Perception Questionnaire for adults. A Kuder - Richardson 20 test of reliability for dichotomous data was performed allowing an estimate of the internal consistency of the measurement scales. It can be seen that, for all three illness groups, internal consistency is acceptable for the timeline and consequences scale. The cure/control scale, however, was not internally consistent for any illness group. As health professionals, we need to develop the means to further understand how paediatric illness beliefs relate to specific disease types, age and psychosocial factors and the utility of this instrument is discussed within this context.

Asthma↗
PubMed2005

MRS of oligodendroglial tumors: correlation with histopathology and genetic subtypes.

BACKGROUND: Oligodendroglial neoplasms with combined loss of chromosomes 1p and 19q may have a good prognosis and respond to procarbazine-lomustine (CCNU)-vincristine (PCV) chemotherapy. OBJECTIVE: To determine whether single voxel magnetic resonance spectroscopy (SV-MRS) obtained through routine clinical practice distinguishes between histopathologic and genetic subtypes of oligodendroglial tumors. METHODS: Forty-eight patients with oligodendroglial tumors (19 oligodendrogliomas and 29 oligoastrocytomas) underwent molecular genetic analysis to determine allelic imbalance in chromosomes 1p36 and 19q13. SV-MRS was obtained pretherapy to determine tumor metabolite ratios. RESULTS: Grade III oligodendroglial tumors had higher choline (Mann-Whitney; p = 0.002), methyl lipid (Mann-Whitney; p = 0.002), and combined methylene lipid and lactate ratios (Mann-Whitney; p < 0.001) than grade II tumors. Lactate did not distinguish between tumor types (Fisher exact test; p = 0.342) or grade (Fisher exact test; p = 0.452). There were no significant associations when tumors were analyzed according to histopathology or genetic subtypes. CONCLUSION: As a noninvasive diagnostic tool used in routine clinical practice, SV-MRS has the potential benefit of determining oligodendroglial tumor grade but not subtypes classified by histopathology or molecular genetics. MRS may be useful for determining the timing of therapy but is unlikely to predict chemosensitivity.

Adult↗
PubMed2005

The heavy metal content of skeletons from an ancient metalliferous polluted area in southern Jordan with particular reference to bioaccumulation and human health.

This paper considers pollution/toxicological science in an archaeological context. Copper mining was an important activity in southern Jordan, especially during the Bronze Age, Nabatean, Roman, and Byzantine periods, and the environmental legacy of such intensive mining and smelting activities exists today in the form of massive, ancient spoil and smelting tips. The environment was heavily polluted by copper, lead, and other cations during these early periods and the effects of such pollutants continue into modern times. Samples of goat, sheep, and Bronze Age and Byzantine skeletons have been analyzed and high metal loads, from uptake by diverse processes, are reported. Emphasis is placed on the importance of sampling procedure and sample location, bioaccumulation, and the partitioning of such elements. Implications of such pollutants in terms of environmental and human health in ancient and modern times are discussed. Teeth are found to provide excellent vehicles for the monitoring of pollution in both ancient and recent times. Bronze Age skeletons exhibited chemical fingerprints different from those of the Byzantine period.

Animals↗
PubMed2004

What is the impact of consultant supervision on outpatient follow-up rate?

This study investigated the impact of consultants on recycling rates of patients in the ENT outpatient clinic. A retrospective case review of 4205 consecutive patients who attended ENT outpatient clinics of an UK teaching hospital over a 3-month period was conducted. There was a significant association between grade of medical staff and recycling rate of new patients, and also for review patients. Junior doctors have lower recycling rates in consultant-led clinics compared with clinics in the absence of consultants for both new patients (consultant-led 41.0%, without consultant 60.1%; P < 0.01) and old patients (consultant-led 48.9%, without consultant 65.0%; P < 0.01). Individual consultant's practice was reflected upon the overall recycling rate of the clinic as a whole (r = 0.94, P = 0.001). In conclusion, individual consultant's practice dictated recycling rate in the ENT outpatient clinic. Junior doctors were less likely to make follow-up appointments when directly supervised by their consultants.

Appointments and Schedules↗
PubMed2003

Immunogenicity of a recombinant human immunodeficiency virus (HIV)-canarypox vaccine in HIV-seronegative Ugandan volunteers: results of the HIV Network for Prevention Trials 007 Vaccine Study.

In the first preventative human immunodeficiency virus (HIV) vaccine study to be carried out in Africa, 40 HIV-seronegative Ugandan volunteers were randomly assigned to receive a canarypox vector containing HIV-1 clade B (env and gag-pro) antigens (ALVAC-HIV; n = 20), control vector containing the rabies virus glycoprotein G gene (n = 10), or saline placebo (n = 10). Cytotoxic T lymphocyte activity against target cells expressing clade A, B, and D antigens was assessed using standard chromium-release and confirmatory interferon-gamma enzyme-linked immunospot (ELISPOT) assays. Neutralizing antibody responses to cell line-adapted strains and primary isolates in all 3 clades were also tested. Twenty percent of vaccine recipients generated detectable cytolytic responses to either Gag or Env, and 45% had vaccine-induced HIV-specific CD8(+) T cell responses, as measured by the ELISPOT assay. In contrast, only 5% of the control group had vaccine-specific responses. Neutralizing antibodies against primary and laboratory-adapted HIV-1 clade B strains were seen in 10% and 15% of vaccine recipients, respectively, but responses against clades A and D were not detected. Although the immunogenicity of this clade B-based vaccine was low, ALVAC-HIV elicited CD8(+) T cell responses with detectable cross-activity against clade A and D antigens in a significant proportion of vaccine recipients.

AIDS Vaccines↗
PubMed2003

Combined use of maternal, paternal and bi-parental genetic markers for the identification of wolf-dog hybrids.

The identification of hybrids is often a subject of primary concern for the development of conservation and management strategies, but can be difficult when the hybridizing species are closely related and do not possess diagnostic genetic markers. However, the combined use of mitochondrial DNA (mtDNA), autosomal and Y chromosome genetic markers may allow the identification of hybrids and of the direction of hybridization. We used these three types of markers to genetically characterize one possible wolf-dog hybrid in the endangered Scandinavian wolf population. We first characterized the variability of mtDNA and Y chromosome markers in Scandinavian wolves as well as in neighboring wolf populations and in dogs. While the mtDNA data suggested that the target sample could correspond to a wolf, its Y chromosome type had not been observed before in Scandinavian wolves. We compared the genotype of the target sample at 18 autosomal microsatellite markers with those expected in pure specimens and in hybrids using assignment tests. The combined results led to the conclusion that the animal was a hybrid between a Scandinavian female wolf and a male dog. This finding confirms that inter-specific hybridization between wolves and dogs can occur in natural wolf populations. A possible correlation between hybridization and wolf population density and disturbance deserves further research.

Animals↗
PubMed2003

Selenium protects primary human keratinocytes from apoptosis induced by exposure to ultraviolet radiation.

The generation of reactive oxygen species has been implicated in ultraviolet radiation (UVR)-induced skin damage. In mice, increasing dietary selenium intake protects skin from UVR-induced DNA damage and photocarcinogenesis. We sought to determine whether selenium supplementation could protect keratinocytes from apoptosis resulting from exposure to broadband (TL20W/12) UVR. Unirradiated cultures contained 6.5 +/- 1% apoptotic cells; the maximum percentage of apoptotic cells (34 +/- 5%) was seen 16 h after UVR of 600 J/m(2). Under these conditions cell death from necrosis was 15 +/- 2.5% of the total cells. A 24-h preincubation with sodium selenite (10 nm(-1) microm) or selenomethionine (50 nm(-1) microm) protected cultured human keratinocytes from UVR-induced apoptosis. In primary keratinocytes the greatest reduction in apoptosis was found with 100 nm of either selenium compound (71% reduction in the numbers of total apoptotic cells; P < 0.01). Supplementation with 100-200 nm selenite or selenomethionine prevented UVR-induced apoptosis, but did not decrease the levels of UVR-induced p53, as measured by Western blotting. Collectively, this data suggests that selenium prevents UVR-induced cell death by inhibiting p53-independent cell death pathways.

Acridine Orange↗
PubMed2003

Sputum T lymphocytes in asthma, COPD and healthy subjects have the phenotype of activated intraepithelial T cells (CD69+ CD103+).

BACKGROUND: T cells of intraepithelial phenotype have previously been detected in bronchoalveolar lavage (BAL) fluid in a range of lung diseases; these cells express the adhesion molecule alpha(E)beta(7) integrin, CD103, the ligand for epithelial cell E-cadherin. In subjects with asthma CD4+ lymphocytes are the predominant T cell subtype found in bronchial biopsy specimens and in BAL fluid, whereas CD8+ lymphocytes have been shown to predominate in subjects with chronic obstructive pulmonary disease (COPD). The aim of this study was to analyse the expression of CD103, activation markers (CD25 and CD69), and chemokine receptors (CXCR3, CCR5 and CCR3) on CD4+ and CD8+ lymphocytes from sputum and peripheral blood of subjects with asthma, COPD, and healthy controls. METHODS: T cell surface markers were assessed by immunofluorescence labelling and flow cytometry of gated lymphocytes among CD45+ leucocytes in sputum cell suspensions. RESULTS: Sputum lymphocytes expressed higher levels of CD103 and CD69 than blood lymphocytes in all subject groups, with CD103 expressed at higher levels on CD8+ than on CD4+ cells. There were no detectable differences in numbers of CD4+ and CD8+ T cells between subjects with asthma, COPD and controls. The percentage of sputum lymphocytes expressing CXCR3 was lower in subjects with asthma or COPD than in healthy controls; CCR3 was not detectable on sputum or blood lymphocytes. CONCLUSIONS: Sputum T lymphocytes are predominantly of activated intraepithelial phenotype (CD103+ CD69+), and normal numbers of CD4+ and CD8+ T cell populations are found in the sputum of patients with asthma and COPD.

Adult↗
PubMed2002

DNA markers predicting benefit from adjuvant fluorouracil in patients with colon cancer: a molecular study.

BACKGROUND: Present clinical algorithms assign adjuvant chemotherapy according to prognosis, but clinical decision-making would be greatly improved if reliable predictive markers were available to identify which subsets of patients benefit most from treatment. We examined molecular markers in preserved tissue from patients with Dukes' B or C colon cancer randomised to receive, or not, adjuvant fluorouracil, and assessed each marker's prognostic and predictive value. METHODS: Formalin-fixed paraffin-embedded paired normal and tumour samples were obtained from 393 patients with colon cancer from the UK AXIS trial of postoperative portal vein infusion fluorouracil versus control. We measured loss of heterozygosity (LOH) and microsatellite instability at four loci: P53 (17p13), D18S61 (18q22.3), D18S851 (18q21.1), and DP1 (5q21). The prognostic value of each marker was assessed with the log-rank test, and the predictive value by comparison of treatment hazard ratios with the chi(2) test for heterogeneity (CSH). FINDINGS: In 228 (58%) patients informative for LOH at D18S61, this marker was significantly predictive: benefit from fluorouracil was significantly greater in patients retaining heterozygosity than in those with LOH (CSH p=0.02). Conversely, LOH at D18S61 was a significant prognostic marker of improved outcome in untreated patients. 314 (80%) patients were informative for LOH at at least one of the three 17p and 18q sites, of whom half retained heterozygosity at one or more site. The effect of chemotherapy in these patients was striking (hazard ratio 0.45, 95% CI 0.28-0.73), whereas chemotherapy had no effect in patients with no retained heterozygosity (0.91; 0.56-1.48), CSH p=0.039. INTERPRETATION: Retention of heterozygosity at one or more 17p or 18q sites was associated with the ability to benefit from adjuvant fluorouracil. These results support the principle of developing molecular markers as predictive factors in treatment decisions.

Aged↗