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Biomedical subjects

Richard Wilson

Publications and source records attributed to Richard Wilson.

At least 19 recordsLinked to original sources
PubMed2006

Clinicians didn't reliably distinguish between different causes of cardiac death using case histories.

BACKGROUND AND OBJECTIVES: Routine statistics and epidemiologic studies often distinguish between types of cardiac death. Our aim was to assess agreement between doctors on cause of death given identical clinical information, and to assess agreement between a physician panel and the original cause of death as coded on national statistics. METHODS: Clinical information and autopsy reports on 400 cardiac deaths were randomly selected from a defined population in the West Midlands, UK. A panel of eight clinicians was assembled, and batches of 24-25 cases were sent to pairs of these clinicians who, blinded to the certified cause of death, independently of each other assigned underlying cause of death. Physician panel decision was achieved by consensus. Levels of agreement were assessed using the kappa statistic. RESULTS: Reviewers agreed on cause of death in 54% of cases (kappa = 0.34). Consensus decision of reviewers agreed with death certificate diagnosis in 61.5% (kappa = 0.39). Agreement was higher if an autopsy had been performed (kappa = 0.49). CONCLUSION: The process of identifying underlying cause of death is of limited reliability, and therefore, limited accuracy. This has implications for design of epidemiologic studies and clinical trials of cardiovascular disease.

Adolescent↗
PubMed2006

WARP is a novel multimeric component of the chondrocyte pericellular matrix that interacts with perlecan.

WARP is a novel member of the von Willebrand factor A domain superfamily of extracellular matrix proteins that is expressed by chondrocytes. WARP is restricted to the presumptive articular cartilage zone prior to joint cavitation and to the articular cartilage and fibrocartilaginous elements in the joint, spine, and sternum during mouse embryonic development. In mature articular cartilage, WARP is highly specific for the chondrocyte pericellular microenvironment and co-localizes with perlecan, a prominent component of the chondrocyte pericellular region. WARP is present in the guanidine-soluble fraction of cartilage matrix extracts as a disulfide-bonded multimer, indicating that WARP is a strongly interacting component of the cartilage matrix. To investigate how WARP is integrated with the pericellular environment, we studied WARP binding to mouse perlecan using solid phase and surface plasmon resonance analysis. WARP interacts with domain III-2 of the perlecan core protein and the heparan sulfate chains of the perlecan domain I with K(D) values in the low nanomolar range. We conclude that WARP forms macromolecular structures that interact with perlecan to contribute to the assembly and/or maintenance of "permanent" cartilage structures during development and in mature cartilages.

Amino Acid Motifs↗
PubMed2006

Comparison of cooling systems during islet purification.

Islet isolation is a complex procedure that includes digestion and purification of pancreatic tissue. As we move towards clinical regulatory control and standardization, understanding of the detailed stages of the procedure have become increasingly important. Purification on a COBE 2991 density gradient allows human islets to be separated from a large volume of acinar tissue. Cooling the gradient and tissue is thought to be important to reduce metabolic activity but cooling systems for the gradient are expensive, with limited availability. In this study, the efficiency of cooling methods for the COBE 2991 cell separator has been investigated. The two cooling systems were: a) COBE 2991 modified internally to allow coolant (polyethylene glycol) from a chiller to circulate either side of the spindle and around the bowl (original system), and b) an air-cooled system using an air conditioner to blow cold air into the bowl from above (air cooler system). Cooling required 20 min for the original system and temperature was stabilized within 4-7 degrees C. The air system cooled rapidly but was not stable. There was an increase in the temperature of the medium with using both systems during centrifugation because of heat generated by the COBE machine; however, the temperature of the medium after centrifugation with the air system was significantly higher than that with the original system (13.3 +/- 0.2 degrees C vs. 8.7 +/- 0.7 degrees C, p < 0.05). The original cooler system was found to be more efficient at reducing heat generated by the COBE machine than the air system. Further investigation of the importance of the recorded temperatures is required.

Cell Separation↗
PubMed2005

Molecular study of malignant gliomas treated with epidermal growth factor receptor inhibitors: tissue analysis from North American Brain Tumor Consortium Trials 01-03 and 00-01.

PURPOSE: We investigated the molecular effect of the epidermal growth factor receptor (EGFR) inhibitors erlotinib and gefitinib in vivo on all available tumors from patients treated on North American Brain Tumor Consortium trials 01-03 and 00-01 for recurrent or progressive malignant glioma. EXPERIMENTAL DESIGN: EGFR expression and signaling during treatment with erlotinib or gefitinib were analyzed by Western blot and compared with pre-erlotinib/gefitinib-exposed tissue or unexposed controls. Tumors were also analyzed for EGFR mutations and for other genomic abnormalities by array-based comparative genomic hybridization. Clinical data were used to associate molecular features with tumor sensitivity to erlotinib or gefitinib. RESULTS: Erlotinib and gefitinib did not markedly affect EGFR activity in vivo. No lung signature mutations of EGFR exons 18 to 21 were observed. There was no clear association between erlotinib/gefitinib sensitivity and deletion or amplification events on array-based comparative genomic hybridization analysis, although novel genomic changes were identified. CONCLUSIONS: As erlotinib and gefitinib were generally ineffective at markedly inhibiting EGFR phosphorylation in these tumors, other assays may be needed to detect molecular effects. Additionally, the mechanism of erlotinib/gefitinib sensitivity likely differs between brain and lung tumors. Finally, novel genomic changes, including deletions of chromosomes 6, 21, and 22, represent new targets for further research.

Antineoplastic Agents↗
PubMed2005

Sequence, annotation, and analysis of synteny between rice chromosome 3 and diverged grass species.

Rice (Oryza sativa L.) chromosome 3 is evolutionarily conserved across the cultivated cereals and shares large blocks of synteny with maize and sorghum, which diverged from rice more than 50 million years ago. To begin to completely understand this chromosome, we sequenced, finished, and annotated 36.1 Mb ( approximately 97%) from O. sativa subsp. japonica cv Nipponbare. Annotation features of the chromosome include 5915 genes, of which 913 are related to transposable elements. A putative function could be assigned to 3064 genes, with another 757 genes annotated as expressed, leaving 2094 that encode hypothetical proteins. Similarity searches against the proteome of Arabidopsis thaliana revealed putative homologs for 67% of the chromosome 3 proteins. Further searches of a nonredundant amino acid database, the Pfam domain database, plant Expressed Sequence Tags, and genomic assemblies from sorghum and maize revealed only 853 nontransposable element related proteins from chromosome 3 that lacked similarity to other known sequences. Interestingly, 426 of these have a paralog within the rice genome. A comparative physical map of the wild progenitor species, Oryza nivara, with japonica chromosome 3 revealed a high degree of sequence identity and synteny between these two species, which diverged approximately 10,000 years ago. Although no major rearrangements were detected, the deduced size of the O. nivara chromosome 3 was 21% smaller than that of japonica. Synteny between rice and other cereals using an integrated maize physical map and wheat genetic map was strikingly high, further supporting the use of rice and, in particular, chromosome 3, as a model for comparative studies among the cereals.

Arabidopsis↗
PubMed2005

Linkage of ambulance service and accident and emergency department data: a study of assault patients in the west midlands region of the UK.

OBJECTIVE: The objectives of this study are to determine whether it is possible to link ambulance service and Emergency Department (ED) data for assault patients, to look at the potential advantages of this linkage and to investigate the quality of coding in the two data sets. DATA AND METHODS: Data from West Midlands Ambulance Service and seven EDs in the urban West Midlands were linked using probabilistic linkage. The linked data were analysed to investigate demography, priority category, diagnosis, conscious level, disposal and assault coding. PRINCIPAL FINDINGS: 84.2% of the ambulance records were linked to an ED record. Only 40.7% of the linked records were coded as assault in the ED data and only 46.7% of ED assault cases brought by ambulance could be linked. 77.6% of all assault injuries were to the head, face and neck. Only 1.0% of patients presented with coma. 12.0% of all assault patients and 53.5% of the highest priority cases were admitted. CONCLUSIONS: Data linkage is possible and can increase the amount of information available. Data quality problems were identified in both datasets, which has implications for the monitoring and prevention of assaults. The use of a common identifier would aid the following of patient pathways.

Adolescent↗
PubMed2005

Misfolding of collagen X chains harboring Schmid metaphyseal chondrodysplasia mutations results in aberrant disulfide bond formation, intracellular retention, and activation of the unfolded protein response.

Collagen X is a short chain collagen expressed specifically by the hypertrophic chondrocytes of the cartilage growth plate during endochondral bone formation. Accordingly, COL10A1 mutations disrupt growth plate function and cause Schmid metaphyseal chondrodysplasia (SMCD). SMCD mutations are almost exclusively located in the NC1 domain, which is crucial for both trimer formation and extracellular assembly. Several mutations are expected to reduce the level of functional collagen X due to NC1 domain misfolding or exclusion from stable trimer formation. However, other mutations may be tolerated within the structure of the assembled NC1 trimer, allowing mutant chains to exert a dominant-negative impact within the extracellular matrix. To address this, we engineered SMCD mutations that are predicted either to prohibit subunit folding and assembly (NC1del10 and Y598D, respectively) or to allow trimerization (N617K and G618V) and transfected these constructs into 293-EBNA and SaOS-2 cells. Although expected to form stable trimers, G618V and N617K chains (like Y598D and NC1del10 chains) were secreted very poorly compared with wild-type collagen X. Interestingly, all mutations resulted in formation of an unusual SDS-stable dimer, which dissociated upon reduction. As the NC1 domain sulfhydryl group is not solvent-exposed in the correctly folded NC1 monomer, disulfide bond formation would result only from a dramatic conformational change. In cells expressing mutant collagen X, we detected significantly increased amounts of the spliced form of X-box DNA-binding protein mRNA and up-regulation of BiP, two key markers for the unfolded protein response. Our data provide the first clear evidence for misfolding of SMCD collagen X mutants, and we propose that solvent exposure of the NC1 thiol may trigger the recognition and degradation of mutant collagen X chains.

Amino Acid Sequence↗
PubMed2005

Mutations of COL10A1 in Schmid metaphyseal chondrodysplasia.

Schmid metaphyseal chondrodysplasia (SMCD) is a dominantly inherited cartilage disorder caused by mutations in the gene for the hypertrophic cartilage extracellular matrix structural protein, collagen X (COL10A1). Thirty heterozygous mutations have been described, about equally divided into two mutation types, missense mutations, and mutations that introduce premature termination signals. The COL10A1 mutations are clustered (33/36) in the 3' region of exon 3, which codes for the C-terminal NC1 trimerization domain. The effect of COL10A1 missense mutations have been examined by in vitro expression and assembly assays and cell transfection studies, which suggest that a common consequence is the disruption of collagen X trimerization and secretion, with consequent intracellular degradation. The effect of COL10A1 nonsense mutations in cartilage tissue has been examined in two patients, demonstrating that the mutant mRNA is completely removed by nonsense mediated mRNA decay. Thus for both classes of mutations, functional haploinsufficiency is the most probable cause of the clinical phenotype in SMCD.

Child↗
PubMed2005

Level of disagreement between Proview phosphene tonometer and Goldmann applanation tonometer intraocular pressure readings.

PURPOSE: To evaluate the agreement of intraocular pressure (IOP) readings obtained with the Proview phosphene tonometer and those obtained by Goldmann applanation tonometry as well as the effect of regular use of the Proview on patients' anxiety about their glaucoma. METHODS: One hundred thirty-five consecutive patients with glaucoma, 35 designated as controls, were enrolled in a 10-month randomized prospective clinical trial. The study patients but not the controls used the Proview outside the office. At office visits IOP was measured by an ophthalmologist with the Goldmann applanation tonometer (GAT) as well as by examiners and patients using the Proview. Patients in the treatment group (n = 100) were asked to measure and record their IOP at home as well. Using ANOVA, we examined the relationship between demographic variables and the level of agreement between the Proview readings and those measured by GAT at the final office visit. All participants also were asked to complete a questionnaire regarding their anxiety about their IOP at the baseline and final office visits. The primary outcome measure was the level of agreement of the Proview measurements with those obtained by GAT. Secondary outcome measures included patients' anxiety about their glaucoma. RESULTS: The absolute mean difference between GAT and Proview readings at the final visit was 3.5 +/- 2.9 mm Hg (median, 2.8 mm Hg). The treatment group reported significantly less anxiety about their glaucoma after 4 to 6 weeks of using the Proview (P = .024). CONCLUSIONS: There was considerable discrepancy between Proview and GAT readings. However, regular use of the Proview tonometer significantly reduced patients' anxiety about their glaucoma.

Adolescent↗
PubMed2005

Risk assessment for asbestos-related cancer from the 9/11 attack on the World Trade Center.

OBJECTIVE: We sought to estimate the lifetime risk of asbestos-related cancer for residents of Lower Manhattan attributable to asbestos released into the air by the 9/11 attack on New York City's World Trade Center (WTC). METHODS: Exposure was estimated from available data and reasoned projections based on these data. Cancer risk was assessed using an asbestos risk model that differentiates asbestos fiber-types and the US Environmental Protection Agency's model that does not differentiate fiber-types and combines mesothelioma and lung cancer risks. RESULTS: The upper limit for the expected number of asbestos-related cancers is less than one case over the lifetime of the population for the risk model that is specific for fiber-types and 12 asbestos-related cancers with the US Environmental Protection Agency's model. CONCLUSIONS: The cancer risk associated with asbestos exposures for residents of Lower Manhattan resulting from the collapse of the WTC is negligible.

Adolescent↗
PubMed2004

Regional surveillance of accident and emergency department attendances: experiences from the West Midlands.

Information is collected on every patient that attends accident and emergency (A and E). However, there is currently no central collection of these data. In 1999 it was decided to collect data on all A and E attendances in the West Midlands region. All 21 hospitals with 24 h A and E departments were asked to submit data to the Surveillance Centre at the University of Birmingham. To date, 19 hospitals have submitted data but the formats vary leading to a substantial amount of data processing. There are several limitations to the data set, for example a lack of information on the reasons for attendance. Despite this, routinely collected A and E data have great potential for surveillance and the data have been used in original research and to guide local policy. The West Midlands system is the largest source of A and E data in the United Kingdom. This information is of use to a wide range of organizations.

Data Collection↗
PubMed2004

Older people's use of Accident and Emergency services.

INTRODUCTION: It has previously been reported that patients aged over 65 years account for 15% of Accident and Emergency (A&E) attendances. Despite this, there have been few studies looking at older people's use of A&E. This study describes the A&E attendance patterns of older people, defined as those aged 65 years and over, using data from an NHS region over a number of years. Their attendances are also compared with those of the rest of the population. DATA AND METHODS: A&E attendance data were collected for 14 Acute Trusts in the West Midlands for the period from 1 April 1999 to 31 March 2002 via the West Midlands Accident and Emergency Surveillance Centre. RESULTS: Patients aged 65 years and over accounted for 18% of all attendances. Attendance rates were highest in those aged over 80 years. Older patients were significantly more likely to attend during the morning and early afternoon, during the winter months, arrive by ambulance and require admission to hospital. Older patients were significantly more likely to attend with non-injury, particularly cardiac-related conditions. Injuries accounted for 33.1% of attendances in the over-65s compared with 59.9% in the 0-64s. CONCLUSIONS: This study is the first in England to look at the A&E attendance patterns of all older people in an NHS region. It has demonstrated the continued high level use of A&E by those aged over 65 years. This highlights the need for continued systemic monitoring of A&E attendance patterns to enable planners to accommodate the impact of the increasingly ageing population.

Adolescent↗
PubMed2004

EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib.

Somatic mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene are reportedly associated with sensitivity of lung cancers to gefitinib (Iressa), kinase inhibitor. In-frame deletions occur in exon 19, whereas point mutations occur frequently in codon 858 (exon 21). We found from sequencing the EGFR TK domain that 7 of 10 gefitinib-sensitive tumors had similar types of alterations; no mutations were found in eight gefitinib-refractory tumors (P = 0.004). Five of seven tumors sensitive to erlotinib (Tarceva), a related kinase inhibitor for which the clinically relevant target is undocumented, had analogous somatic mutations, as opposed to none of 10 erlotinib-refractory tumors (P = 0.003). Because most mutation-positive tumors were adenocarcinomas from patients who smoked <100 cigarettes in a lifetime ("never smokers"), we screened EGFR exons 2-28 in 15 adenocarcinomas resected from untreated never smokers. Seven tumors had TK domain mutations, in contrast to 4 of 81 non-small cell lung cancers resected from untreated former or current smokers (P = 0.0001). Immunoblotting of lysates from cells transiently transfected with various EGFR constructs demonstrated that, compared to wild-type protein, an exon 19 deletion mutant induced diminished levels of phosphotyrosine, whereas the phosphorylation at tyrosine 1092 of an exon 21 point mutant was inhibited at 10-fold lower concentrations of drug. Collectively, these data show that adenocarcinomas from never smokers comprise a distinct subset of lung cancers, frequently containing mutations within the TK domain of EGFR that are associated with gefitinib and erlotinib sensitivity.

Adenocarcinoma↗
PubMed2004

Risk assessment in the management of patients with ocular hypertension.

PURPOSE: To develop a model for estimating the global risk of disease progression in patients with ocular hypertension and to calculate the "number-needed-to-treat" (NNT) to prevent progression to blindness as an aid to practitioners in clinical decision making. DESIGN: Development of a mathematical model for estimating risk of glaucoma progression. METHODS: Population-based studies of patients with ocular hypertension and glaucoma were reviewed by a panel of glaucoma specialists. Measures of disease progression risks derived from three long-term studies and assumptions based on the available data were used to estimate the risk of progression from ocular hypertension to glaucoma and glaucoma to unilateral blindness for untreated and treated patients over a 15-year period. Using these estimates, the NNT (1/absolute risk reduction on treatment) to prevent unilateral blindness in one patient with ocular hypertension was calculated. RESULTS: In untreated patients, the estimated risk of progression from ocular hypertension to unilateral blindness was 1.5% to 10.5% and in treated patients, the estimated risk of progression was 0.3% to 2.4% over 15 years. From these estimates, between 12 and 83 patients with ocular hypertension will require treatment to prevent one patient from progressing to unilateral blindness over a 15-year period. CONCLUSION: Global risk assessment that incorporates all available data plays a vital role in managing patients with ocular hypertension. A more precise understanding of long-term vision loss should be factored into decisions pertaining to the initiation of glaucoma therapy. Undoubtedly, these estimates will evolve and change with the availability of new population-based epidemiologic information and improvements in multivariable model testing.

Blindness↗
PubMed2004

Applying an evidence-based approach to the management of patients with ocular hypertension: evaluating and synthesizing published evidence.

PURPOSE: The use of evidence-based medicine in managing patients with ocular hypertension has been constrained by the limited availability of high-quality data from controlled clinical trials and by limited formal training of clinicians in evaluating published evidence. This article will provide strategies and techniques to evaluate critically the quality of published research, synthesize the findings, and integrate published evidence in the care of patients with ocular hypertension. DESIGN: Review of the published literature and consensus of a panel of experts. METHODS: The published literature on evidence-based medicine was reviewed. Strategies and techniques in evaluating the quality of evidence and how to integrate evidence into the practice setting using the following three major questions were discussed by a panel of experts: Are the results of the study valid? What are the results? Do the study outcomes apply to individual patient care? RESULTS: Approaches to assessing study validity and the importance of considering the size of the treatment effect and precision of the effect size were detailed. The importance of using the "number-needed-to-treat" as a tool for translating results of clinical trials to individual patient care and the "number-needed-to-harm" as a method of comparing the potential benefit and harm of a given therapy was acknowledged. CONCLUSION: As the volume of high-quality data increases, the information provided herein may help ophthalmologists apply evidence-based medicine techniques as they seek to optimize the care of individual patients with ocular hypertension.

Evidence-Based Medicine↗
PubMed2004

Public attitudes toward smoking bans in a tobacco-producing county.

OBJECTIVES: Allen County, KY, is a rural county with a population of approximately 18,000. The county has a tobacco crop and is in a state in which tobacco interests are influential. The tobacco control program at the public health department developed a goal to reduce environmental tobacco smoke by restricting smoking in public places. To progress toward that goal, a public opinion poll was conducted to determine citizens' views regarding smoking restrictions in the county courthouse. METHODS: A telephone survey was conducted using the Allen County telephone directory as a sampling frame. The survey instrument included questions on support for smoking restrictions in the courthouse, restaurants, and workplaces as well as support for increasing Kentucky's cigarette tax. Interviews with 374 individuals--53.6% of the initial sample--were completed. RESULTS: Banning all smoking in the Allen County Courthouse was supported by 163 (43.4%) of the respondents. Designated smoking areas were supported by 168 (44.7%) of the respondents. Twenty-four (6.4%) of the respondents opposed any smoking restrictions at the courthouse. Women were more likely to support a ban on all smoking at the courthouse (45.4% compared with 40%). Males were more likely to support designated smoking areas (46.2% of males versus 43.8% of females). There was a small association between opposition to smoking restrictions at the courthouse and smoking by the respondent. An increase in Kentucky's cigarette tax was supported by 132 (35.1%) of the respondents and opposed by 184 (48.9%). There was no association between ownership of a tobacco-farming allotment and opinion regarding any of the tobacco control measures. CONCLUSIONS: Most Allen County residents support some form of restriction on smoking in public places (including the county courthouse and restaurants) and in workplaces. Only approximately one-third, however, supported an increase in the cigarette tax, perhaps reflecting a general antitax feeling. Ownership of tobacco allotments does not appear to be an important factor in determining attitudes on smoking control issues.

Agriculture↗
PubMed2004

Arsenic in drinking water and bladder cancer mortality in the United States: an analysis based on 133 U.S. counties and 30 years of observation.

This study analyzes the relationship between arsenic exposure through drinking water and bladder cancer mortality. The county-specific white male bladder cancer mortality data (1950-1979) and county-specific groundwater arsenic concentration data were obtained for 133 U.S. counties known to be exclusively dependent on groundwater for their public drinking water supply. No arsenic-related increase in bladder cancer mortality was found over the exposure range of 3 to 60 microg/L using stratified analysis and regression analyses (both unweighted and weighted by county population and using both mean and median arsenic concentrations). These results, which provide a direct estimate of arsenic-related cancer risk for U.S. residents, exclude the National Research Council's 2001 risk estimate that was based on Southwest Taiwan data and required adjusting for differences between the body mass and water consumption rates of U.S. and Taiwanese residents.

Adult↗