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Biomedical subjects

K Williams

Publications and source records attributed to K Williams.

At least 37 records · Page 2Linked to original sources
PubMed2004

Validity and reliability of a questionnaire to measure the impact of lower urinary tract symptoms on quality of life: the Leicester Impact Scale.

AIMS: To develop a condition specific quality of life measure for males and females with urinary storage symptoms of urgency, frequency, nocturia and incontinence. MATERIALS AND METHODS: A sample of community dwelling males and females aged 40 years or more who were taking part in an epidemiological study provided data for development and validation of the scale. Questions were developed from literature review and discussions with clinicians and patients. Inclusion of items was dependent on levels of missing data and principal components analysis. Validity was assessed by comparison with the Hospital Anxiety and Depression Scale, the Bradburn Negative Affect Scale and single questions concerning the problematic nature of symptoms. Construct validity was assessed by comparing cases and non-cases, and patients with different symptom patterns. Test-retest and inter-rater reliability statistics were calculated for individual items. Responsiveness to change was measured in subjects taking part in a randomised controlled trial of a nursing intervention. RESULTS: The scale showed high levels of internal consistency and measures of construct validity were as hypothesised. Test-retest and inter-rater reliability was moderate to excellent. The distribution of scores was skewed with low levels of impact but the questionnaire was responsive to conservative treatments in patients receiving a nursing intervention. CONCLUSIONS: The questionnaire proved to be a valid and reliable interviewer administered instrument for measuring impact of urinary symptoms.

Aged↗
PubMed2004

Use of water-equivalent plastic scintillator for intravascular brachytherapy dosimetry.

Beta irradiation has recently been investigated as a possible technique for the prevention of restenosis in intravascular brachytherapy after balloon dilatation or stent implantation. Present methods of beta radiation dosimetry are primarily conducted using radiochromic film. These film dosimeters exhibit limited sensitivity and their characteristics differ from those of tissue, therefore the dose measurement readings require correction factors to be applied. In this work a novel, mini-size (2 mm diameter by 5 mm long) dosimeter element fabricated from Organic Plastic Scintillator (OPS) material was employed. Scintillation photon detection is accomplished using a precision photodiode and innovative signal amplification and processing techniques, rather than traditional photomultiplier tube methods. A significant improvement in signal to noise ratio, dynamic range and stability is achieved using this set-up. In addition, use of the non-saturating organic plastic scintillator material as the detector enables the dosimeter to measure beta radiation at very close distances to the source. In this work the plastic scintillators have been used to measure beta radiation dose at distances of less than 1 mm from an Sr-90 cardiovascular brachytherapy source having an activity of about 2.1 GBq beta radiation levels for both depth-distance and longitudinal profile of the source pellet chain, both in air and in liquid water, are measured using this system. The data obtained is compared with results from Monte Carlo simulation technique (MCNP 4B). Plastic scintillator dosimeter elements, when used in conjunction with photodiode detectors may prove to be useful dosimeters for cardiovascular brachytherapy beta sources, or other applications where precise near-source field dosimetry is required. The system described is particularly useful where measurement of actual dose rate in real time, a high level of stability and repeatability, portability, and immediate access to results are prime requirements.

Beta Particles↗
PubMed2004

Phase I clinical trial of a human idiotypic p53 vaccine in patients with advanced malignancy.

BACKGROUND: The purpose of this study was to induce immunity to p53 by using an idiotypic vaccine, composed of a pool of eight peptides derived from the complimentarity determining regions (CDRs) of human anti-p53 antibodies. PATIENTS AND METHODS: Subjects with advanced malignancy received up to four, monthly intradermal injections of pooled peptides (500 microg of each) admixed with granulocyte-macrophage colony-stimulating factor (GM-CSF; 100 microg). In addition, two sheep and two rabbits were also vaccinated with the pooled peptides. RESULTS: Fourteen subjects were enrolled into the study and six of these completed the vaccination schedule. The vaccine was well tolerated by all subjects and no major adverse events were attributable to the vaccine. All subjects mounted in vivo delayed type hypersensitivity (DTH) responses to two or more of the individual vaccine peptides. Vaccine-induced antibodies specific for peptides 2, 5 or 8 were detected in four of six subjects, and two of these had vaccine-specific, cell-mediated responses. Increasing titers of p53-specific antibodies were found in one patient. No T-cell response to p53 was observed in any of the subjects. All animals developed humoral immunity to the peptides and one of the sheep developed rising serum titers of anti-p53 antibodies. CONCLUSIONS: Vaccination with human antibody CDR regions represents a novel method for inducing human antibodies, which may in turn serve as immunological mimics of p53.

Adult↗
PubMed2004

Mycobacterium saskatchewanense sp. nov., a novel slowly growing scotochromogenic species from human clinical isolates related to Mycobacterium interjectum and Accuprobe-positive for Mycobacterium avium complex.

A pigmented, slowly growing Mycobacterium avium complex AccuProbe-positive organism was isolated from the sputum and pleural fluid of a 72-year-old female with bronchiectasis. The unusual morphology of the organism prompted further identification by 16S rRNA gene sequencing, revealing a perfect identity with previously uncharacterized strain Mycobacterium sp. MCRO 8 (GenBank accession no. X93034), with the closest established species by 16S rDNA analysis being Mycobacterium interjectum. HPLC of the organism corresponded to previously obtained patterns identified as M. interjectum-like and, upon sequence evaluation of a selection of strains with a similar profile, more were subsequently identified as MCRO 8. A total of 16 strains isolated from human respiratory samples were evaluated in the characterization of this novel species, for which the name Mycobacterium saskatchewanense sp. nov. is proposed. The type strain is strain 00-250(T) (=ATCC BAA-544(T)=DSM 44616(T)=CIP 108114(T)).

Bacterial Proteins↗
PubMed2004

Comparing specialist early years provision for speech and language impaired children with mainstream nursery provision in the UK - an application of the Early Childhood Environment Rating Scale (ECERS).

BACKGROUND: This study examines the application of the Early Childhood Environment Rating Scale (ECERS) to specialist early years provision for children with developmental speech and language impairment. The scale, which has been used in the national Effective Provision of Pre-school Education (EPPE) study in the UK comprises seven subscales describing the quality of provision along a continuum centred on the following areas: 'space and furnishings', 'personal care routines', 'language reasoning', 'activities', 'interaction', 'program structure', and 'parents and staff'. METHODS: The ECERS was applied to two nurseries funded by the UK charity I CAN by two researchers with inter-rater-reliability coefficients ranging from 0.91 to 0.96. RESULTS: There were notable differences between the specialist early years provision and 'average' nursery provision in the UK. On 7/8 measures the early years centre scores are markedly higher than average pre-school provisions. The standard of education and care for the pre-school provisions included in the EPPE project ranged from below minimal (for the diversity subscale, ECERS-E) to approaching good (for the space and furnishings subscale). In contrast, the early years centres were rated as between minimal to good on areas such as space and furnishings and good to excellent on all other areas. CONCLUSIONS: Clearly specialist services such as those described offer something different from the average. Given results which suggest the positive effects on the children's language abilities of such services it is quite possible that the distinctive characteristics of the nursery environment are responsible for the positive impact. There is a good case for extending the application of the ECERS as a way of helping those providing specialist services start to detect the active ingredients of the provision.

Child Care↗
PubMed2004

Validation of the Alder Hey Triage Pain Score.

AIMS: To describe the validation and reliability of a new pain tool (the Alder Hey Triage Pain Score, AHTPS) for children at triage in the accident and emergency (A&E) setting. METHODS: A new behavioural observational pain tool was developed because of dissatisfaction with available tools and a lack of confidence in self-assessment scores at triage. The study was conducted in a large paediatric A&E department; 575 children (aged 0-16 years) were included. Inter-rater reliability and various aspects of validity were assessed. In addition this tool was compared to the Wong-Baker self-assessment tool. The children were concurrently scored by a research nurse and triage nurses to assess inter-rater reliability. Construct validity was assessed by comparing the research nurse's triage score with the research nurse reassessment score after intervention and/or analgesia. Known group construct validity was assessed by comparing the research nurse's score at triage with the level of pain of the condition as judged by the discharge diagnosis. Predictive validity was assessed by comparing the research nurse's AHTPS with the level of analgesia needed by each patient. The AHTPS was also compared to a self-assessment score. RESULTS: A high level of inter-rater reliability, kappa statistic 0.84 (95% CI 0.80 to 0.88), was shown. Construct validity was well demonstrated; known group construct validity and predictive validity were also demonstrated to a varying degree. CONCLUSIONS: Results support the use of this observational pain scoring tool in the triage of children in A&E.

Adolescent↗
PubMed2004

Copper-associated hepatopathy in a Mexican fruit bat (Artibeus jamaicensis) and establishment of a reference range for hepatic copper in bats.

Copper toxicity has been described in numerous domestic species. The characteristic lesions include hemoglobinuric nephrosis and piecemeal hepatic necrosis with bile ductular hyperplasia and portal fibrosis. Certain species, such as sheep, are prone to toxicity when exposed to copper in feed, whereas an inherent genetic defect of copper storage is present in some breeds of dogs (Bedlington Terriers, West Highland White Terriers, Doberman Pinschers). In nondomestic species, reference ranges have not been established for copper in internal organs, so the establishment of copper toxicity as a diagnosis is difficult. A case of copper toxicity in a captive Mexican fruit bat is presented. Hepatic copper levels in 16 additional bats, of at least 3 different species, were measured. To the authors' knowledge, this is the first reported case of copper toxicity in a chiropteran.

Animals↗
PubMed2003

Productive infection of cerebellar granule cell neurons by JC virus in an HIV+ individual.

BACKGROUND: In the setting of severe immunosuppression, the polyomavirus JC (JCV) can cause a lytic infection of oligodendrocytes. This demyelinating disease of the CNS white matter (WM) is called progressive multifocal leukoencephalopathy (PML). JCV has a very narrow host-cell range and productive infection of neurons has never been demonstrated. Patient, methods, and results: An HIV-1-infected patient presented with signs of pyramidal tract and cerebellar dysfunction. Brain MRI revealed T2 hyperintensities in the WM of both frontal lobes and cerebellar atrophy. His disease progressed despite therapy and he died 6 months later. In addition to classic PML findings in the frontal lobe WM, autopsy revealed scattered foci of tissue destruction in the internal granule cell layer (IGCL) of the cerebellum. In these foci, enlarged granule cell neurons identified by the neuronal markers MAP-2 and NeuN reacted with antibodies specific for the polyomavirus VP1 capsid protein. Electron microscopy showed 40 nm viral particles, consistent with polyomaviruses, in these granule cell neurons. In addition, JCV DNA was detected by PCR after laser capture microdissection of cells from the areas of focal cell loss. Finally, in situ hybridization studies demonstrated that many granule cell neurons were infected with JCV but did not contain viral proteins. Sequence analysis of the JCV regulatory region from cerebellar virions showed a tandem repeat pattern also found in PML lesions of the frontal lobe WM. CONCLUSION: JCV can productively infect granule cell neurons of the IGCL of the cerebellum. This suggests a role for JCV infection of neurons in cerebellar atrophy occurring in HIV-infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Association between polymorphisms of the atrial natriuretic peptide gene and proteinuria: a population-based study.

AIMS/HYPOTHESIS: In case-control studies, polymorphisms at the atrial natriuretic peptide gene (ANP) locus have been associated with presence of albuminuria in Type 1 and Type 2 diabetes. We evaluated the relationship between the ScaIand BstxI polymorphisms and albuminuria in the general population of the Mexico City Diabetes Study. METHODS: Allele/genotype frequencies were analysed by PCR-RFLP analysis using ScaI (wild, A(2) vs mutated, A(1)) and BstxI (wild, C(708) vs mutated, T(708)) enzyme. RESULTS: Among 1288 subjects, hypertension was present in 112 subjects, Type 2 diabetes in 191 and impaired glucose tolerance in 136; microalbuminuria was present in 464 subjects, and clinical proteinuria in 199. General frequencies were 0.93 and 0.96 for the wild alleles, and 0.07 and 0.04 for the mutated alleles, respectively for ScaI and BstxI. Frequency of A(1)was 0.08 in normoalbuminuric, 0.05 in microalbuminuric, and 0.05 in proteinuric patients (chi(2)=7.3, p=0.025). Frequency of T(708) was 0.06 in normoalbuminuric and 0.03 microalbuminuric and 0.03 in proteinuric subjects (chi(2)=8.1, p=0.017). By multivariate analysis, the associations between A(1)or T(708) allele and albuminuria were independent of age, sex, BMI, diabetes, and hypertension, (odds ratio (OR) 0.60, p=0.01, (OR) 0.51, p=0.004, respectively). CONCLUSION/INTERPRETATION: In the general population of Mexico City, both polymorphisms of ANP are associated with albuminuria independently of hypertension, and could play a role in protecting subjects against development of albuminuria.

Adult↗
PubMed2003

Maternal transcranial Doppler in pre-eclampsia and eclampsia.

Pre-eclampsia affects 3-7% of women and is associated with significant maternal and perinatal morbidity and mortality. Transcranial Doppler (TCD) has been used in pre-eclampsia/eclampsia to evaluate non-invasively the cerebrovascular hemodynamics in the maternal middle cerebral artery. TCD has demonstrated in pre-eclamptic women maternal cerebral vasospasm, which does not correlate with mean arterial pressure assessed simultaneously. Estimated cerebral perfusion pressure, assessed using a modified formula, has been shown to be increased in women with severe and non-severe pre-eclampsia. However, in severe pre-eclampsia, elevated cerebral perfusion pressure is counterbalanced by increases in cerebrovascular resistance and cerebral blood flow is unaffected. In eclampsia a significant fall in cerebral vascular resistance occurs which, in the presence of increases in cerebral perfusion pressure, leads to hyperperfusion. Cerebral vascular changes to date have not been sensitive enough to predict the development of pre-eclampsia or eclampsia. Longitudinal studies with the aim of predicting the onset of pre-eclampsia and to assess the effects of various drugs on the maternal cerebral circulation need to be designed.

Blood Flow Velocity↗
PubMed2003

The presentation of aggressive children and adolescents to emergency departments in Western Sydney.

AIM: To examine the utilization characteristics of children and adolescents with aggression presenting to emergency departments (ED) in Western Sydney. METHODS: Retrospective chart review of children and adolescents who presented with aggression to five non-psychiatric emergency departments over a 5-year period. Data were linked with the National Coroner's Information System Database. RESULTS: There were 279 index presentations by children and adolescents (66% male) with aggression. One hundred and seventeen (42%) were 14 years or under. The majority presented after working hours and/or on weekends (62%). Fifty-three percent of presentations had a self-harm component. In 26% of presentations, there was no documentation of mental health involvement. Children were discharged in 62% of presentations. Sixty-eight (24%) children and adolescents subsequently re-presented on 135 occasions with self-harm and/or aggression over the 5-year period. Four (1%) adolescents died. CONCLUSION: A presentation to an ED with aggression by a child or adolescent is an indicator of significant psychosocial dysfunction. These children and adolescents present when services are least accessible and are at risk of re-presentation and death. To address this issue, systems need to be developed that facilitate collaboration between EDs and child and adolescent mental health services.

Adolescent↗
PubMed2003

Birth prevalence of Prader-Willi syndrome in Australia.

This is the first population based study to estimate the birth prevalence of DNA proven Prader-Willi syndrome. Thirty infants were reported to the Australian Paediatric Surveillance Unit between 1998 and 2000, a prevalence of 4 per 100,000 live births or approximately 1/25,000 live births per annum.

Adolescent↗
PubMed2003

The effect of temporal variation in biochemical markers of trisomy 21 across the first and second trimesters of pregnancy on the estimation of individual patient-specific risks and detection rates for Down's syndrome.

BACKGROUND: In a previous study we examined the changes in the median multiple of the median (MoM) with gestation of free beta human chorionic gonadotrophin (F beta-hCG), total human chorionic gonadotrophin (ThCG), alpha-fetoprotein (AFP) and pregnancy-associated plasma protein A (PAPP-A) in a large series of Down's syndrome pregnancies. Results showed that there was a significant temporal variation of the MoM for each marker. In this paper, we assess the impact of this temporal shift on the estimation of patient-specific risks and the detection rates (DRs) for Down's syndrome pregnancies. METHODS: Individual patient-specific risks, DRs and false positive rates were estimated using statistical modelling techniques and computer simulations. The data for these simulations were the regressed mean log(10) analyte MoMs, marker standard deviations (as log(10) MoM) and correlation coefficients derived from the analysis of over 1000 cases of Down's syndrome and 150,000 unaffected pregnancies between 6 and 20 weeks of gestation reported in our previous study. Two models were compared: the classical constant median separation model, which assumes no variation in median shift with gestation (model 1), and a variable median separation model (model 2), which takes account of the changes in median shift with gestation as described in our previous study. RESULTS: When individual patient-specific risks calculated for various MoM values using model 1 were compared with those derived from model 2, considerable differences in risk estimates were observed for all marker combinations, particularly in the first trimester. Using a 1 in 250 cut-off risk, DRs at each gestation in the second trimester for the AFP+F beta-hCG combination were maximized at 14-17 weeks of gestation and were virtually identical at 63-65% for model 1 and model 2. A similar trend was observed for the AFP+ThCG combination, with an optimum gestational range of 15-18 weeks and DRs of 66-68%. In the first trimester, using a 1 in 250 cut-off risk, DRs were more variable with gestation for the prime marker combination of F beta-hCG+PAPP-A, varying from 73% at 8 weeks to 65% at 13 weeks with model 1 and from 75% to 66% with model 2. CONCLUSION: Risk algorithms should take into account temporal variation in marker MoMs in order to produce accurate patient-specific risks. This also helps to maximize DRs, particularly when samples are taken out with the optimal gestational range.

Biomarkers↗
PubMed2002

Expression of oestrogen receptor beta (ERbeta1) protein in human breast cancer biopsies.

Oestrogen action is mediated via specific receptors that act as ligand-activated transcription factors. A monoclonal antibody specific to the C-terminus of human oestrogen receptor beta has been characterized and the prevalence of expression of oestrogen receptor beta protein investigated in a well defined set of breast cancers. Reverse transcription-polymerase chain reaction analysis of RNA from tissue biopsies detected oestrogen receptor beta in all samples examined. The anti-oestrogen receptor beta antibody cross reacted specifically with both long (approximately 59 Kd) and short (approximately 53 Kd) forms of recombinant oestrogen receptor beta. Western blot analysis of breast tumours contained both forms of oestrogen receptor beta protein although in some samples lower molecular weight species (32--45 Kd) were identified. Fifty-one breast cancer biopsies were examined using immunohistochemistry; 41 (80%) were immunopositive for oestrogen receptor alpha, 48 (94%) were immunopositive for oestrogen receptor beta and 38 (74.5%) co-expressed both receptors. Expression of oestrogen receptor beta was exclusively nuclear and occurred in multiple cell types. There was no quantitative relationship between staining for the two ERs although in tumours in which both receptors were present immunoexpression of oestrogen receptor alpha was invariably more intense. The significance of oestrogen receptor beta protein expression in breast cancers to therapy remains to be determined but the availability of a well characterized antibody capable of detecting oestrogen receptor beta in archive material will facilitate the process.

Antibodies, Monoclonal↗
PubMed2002

The Australian Childhood Dementia Study.

OBJECTIVES: To estimate the prevalence of childhood dementia, identify aetiological factors, and provide a brief survey of the psychosocial impact of childhood dementia. METHOD: The Australian Paediatric Surveillance Unit (APSU) was used to identify children with dementia. A total of 224 cases were notified about the dementia study and 141 (63%) questionnaires were completed and returned. Ascertainment was restricted to those most likely to have progressive neurocognitive decline because of practitioner bias against reporting non-progressive cases as dementia. RESULTS: Eighty children with dementia were identified. The estimated prevalence for dementia in childhood in Australian was 5.6/100,000. Thirteen cases (16%) were notified before the age of two years. Seventeen (21%) children were reported to have uncertain or unknown aetiology. Impact upon day to day family functioning was reported by clinicians to be 'marked' or 'extreme' in 50 (63%) families. Only four (6%) clinicians judged present services to be 'very adequate', while 16 (20%) clinicians judged current psychological support for the needs of the family to be 'very' or 'moderately inadequate'. Dementia as an overarching diagnostic concept offers integrative possibilities for research, management and service planning and provision. Childhood disintegrative disorder as a concept is criticised.

Adolescent↗
PubMed2002

Effects of hexachlorobenzene on embryonic mammalian cells.

Hexachlorobenzene (HCB) is a persistent organic pollutant that has been found to be bioaccumulating in several Arctic regions of the world. The response of embryonic cells to HCB exposure has been evaluated for several different cytotoxic responses, including genotoxic effects. NIH 3T3 (mouse) and WS1 (human) embryonic cells were exposed to HCB at 1 and 10 times the average newborn cord blood concentrations of Alaska Arctic natives. Assays were then performed to determine the subsequent effects of HCB on overall cell number, viability, cell growth fraction and long-term survival, as well as specific biochemical and molecular responses. Exposure of both cell types to HCB results in cell membrane damage, a short-term decrease in cell number, increased DNA strand breaks, and a long-term decrease in colony survival. WS1 cells also undergo cell-cycle arrest and modulations in glutathione concentration after exposure to HCB. In addition, NIH 3T3 cells exhibit an increased number of transformed foci after repeated exposure to HCB. This study demonstrates that relevant environmental concentrations of HCB have significant effects on mammalian embryonic cells in culture.

3T3 Cells↗