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Biomedical subjects

S Keenan

Publications and source records attributed to S Keenan.

At least 19 recordsLinked to original sources
PubMed2005

The Vertebrate Genome Annotation (Vega) database.

The Vertebrate Genome Annotation (Vega) database (http://vega.sanger.ac.uk) has been designed to be a community resource for browsing manual annotation of finished sequences from a variety of vertebrate genomes. Its core database is based on an Ensembl-style schema, extended to incorporate curation-specific metadata. In collaboration with the genome sequencing centres, Vega attempts to present consistent high-quality annotation of the published human chromosome sequences. In addition, it is also possible to view various finished regions from other vertebrates, including mouse and zebrafish. Vega displays only manually annotated gene structures built using transcriptional evidence, which can be examined in the browser. Attempts have been made to standardize the annotation procedure across each vertebrate genome, which should aid comparative analysis of orthologues across the different finished regions.

Animals↗
PubMed2005

Ensembl 2005.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of large genome sequences. Over the last year the number of genomes available from the Ensembl site has increased by 7 to 16, with the addition of the six vertebrate genomes of chimpanzee, dog, cow, chicken, tetraodon and frog and the insect genome of honeybee. The majority have been annotated automatically using the Ensembl gene build system, showing its flexibility to reliably annotate a wide variety of genomes. With the increased number of vertebrate genomes, the comparative analysis provided to users has been greatly improved, with new website interfaces allowing annotation of different genomes to be directly compared. The Ensembl software system is being increasingly widely reused in different projects showing the benefits of a completely open approach to software development and distribution.

Animals↗
PubMed2005

Effects of methylphenidate on cognition and apathy in normal pressure hydrocephalus: a case study and review.

The psychostimulant methylphenidate has been previously shown to improve cognitive performance in both normal control volunteers and patient populations. In the present case study, the effects of methylphenidate on cognitive and behavioural function were examined in a single patient with idiopathic normal pressure hydrocephalus (NPH) who had undergone ventriculoperitoneal shunting. A double-blind placebo-controlled ABBA drug design was employed, with the administration of two different doses of methylphenidate followed by neuropsychological assessment on a number of psychometric tests and cognitive tasks drawn from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Methylphenidate produced a dose-dependent positive improvement in behavioural measures in the patient associated with a reduction in apathy. It also had a dose-independent enhancing effect on performance of a Spatial Recognition task. These findings require replication in a large sample of patients to determine whether methylphenidate may prove to be generally useful in enhancing cognition and reducing apathy in normal pressure hydrocephalus.

Aged↗
PubMed2004

DNA sequence and analysis of human chromosome 9.

Chromosome 9 is highly structurally polymorphic. It contains the largest autosomal block of heterochromatin, which is heteromorphic in 6-8% of humans, whereas pericentric inversions occur in more than 1% of the population. The finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs and represents >99.6% of the region. Analysis of the sequence reveals many intra- and interchromosomal duplications, including segmental duplications adjacent to both the centromere and the large heterochromatic block. We have annotated 1,149 genes, including genes implicated in male-to-female sex reversal, cancer and neurodegenerative disease, and 426 pseudogenes. The chromosome contains the largest interferon gene cluster in the human genome. There is also a region of exceptionally high gene and G + C content including genes paralogous to those in the major histocompatibility complex. We have also detected recently duplicated genes that exhibit different rates of sequence divergence, presumably reflecting natural selection.

Base Composition↗
PubMed2004

Ensembl 2004.

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organize biology around the sequences of large genomes. It is a comprehensive and integrated source of annotation of large genome sequences, available via interactive website, web services or flat files. As well as being one of the leading sources of genome annotation, Ensembl is an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements. The facilities of the system range from sequence analysis to data storage and visualization and installations exist around the world both in companies and at academic sites. With a total of nine genome sequences available from Ensembl and more genomes to follow, recent developments have focused mainly on closer integration between genomes and external data.

Animals↗
PubMed2001

Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress.

Erythropoietin (EPO) promotes neuronal survival after hypoxia and other metabolic insults by largely unknown mechanisms. Apoptosis and necrosis have been proposed as mechanisms of cellular demise, and either could be the target of actions of EPO. This study evaluates whether antiapoptotic mechanisms can account for the neuroprotective actions of EPO. Systemic administration of EPO (5,000 units/kg of body weight, i.p.) after middle-cerebral artery occlusion in rats dramatically reduces the volume of infarction 24 h later, in concert with an almost complete reduction in the number of terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling of neurons within the ischemic penumbra. In both pure and mixed neuronal cultures, EPO (0.1--10 units/ml) also inhibits apoptosis induced by serum deprivation or kainic acid exposure. Protection requires pretreatment, consistent with the induction of a gene expression program, and is sustained for 3 days without the continued presence of EPO. EPO (0.3 units/ml) also protects hippocampal neurons against hypoxia-induced neuronal death through activation of extracellular signal-regulated kinases and protein kinase Akt-1/protein kinase B. The action of EPO is not limited to directly promoting cell survival, as EPO is trophic but not mitogenic in cultured neuronal cells. These data suggest that inhibition of neuronal apoptosis underlies short latency protective effects of EPO after cerebral ischemia and other brain injuries. The neurotrophic actions suggest there may be longer-latency effects as well. Evaluation of EPO, a compound established as clinically safe, as neuroprotective therapy in acute brain injury is further supported.

Animals↗
PubMed2000

Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury.

Erythropoietin (EPO), recognized for its central role in erythropoiesis, also mediates neuroprotection when the recombinant form (r-Hu-EPO) is directly injected into ischemic rodent brain. We observed abundant expression of the EPO receptor at brain capillaries, which could provide a route for circulating EPO to enter the brain. In confirmation of this hypothesis, systemic administration of r-Hu-EPO before or up to 6 h after focal brain ischemia reduced injury by approximately 50-75%. R-Hu-EPO also ameliorates the extent of concussive brain injury, the immune damage in experimental autoimmune encephalomyelitis, and the toxicity of kainate. Given r-Hu-EPO's excellent safety profile, clinical trials evaluating systemically administered r-Hu-EPO as a general neuroprotective treatment are warranted.

Animals↗
PubMed1999

How to use the results of an economic evaluation.

BACKGROUND: Given the high costs of delivering care to critically ill patients, practitioners and policymakers are beginning to scrutinize the costs and outcomes associated with intensive care. Health economics is a discipline concerned with determining the best way of using resources to maximize the health of the community. This involves addressing questions such as which procedure, test, therapy, or program should be provided, and to whom, given available resources. PURPOSE: The purpose of this article is to review general economic principles that will help intensivists to better interpret published economic evaluations. DATA SOURCES: Selected articles from the health economics and critical care literature. RESULTS: In this article, we use an economic evaluation that examines sedation strategies in critically ill patients. We discuss how learning to critically appraise an economic evaluation is only part of the task for end users. Determining whether and how to apply the results of economic evaluations to local settings presents bigger challenges and remains largely a matter of judgment. CONCLUSIONS: Economic evaluations use analytic techniques to systematically consider all possible costs and consequences of clinical actions. Although they should never form the sole basis for clinical decisions for individual patients, economic evaluations offer potentially useful information at different levels of decision-making.

Cost-Benefit Analysis↗
PubMed1997

Planning for the future: the experience of implementing a children's day assessment unit in a district general hospital.

A paediatric day assessment unit was opened in May 1995. An audit of the first year's activity showed that, despite an increase in emergency admissions of 8.4%, the number of children admitted as an emergency overnight was reduced by 3% in paediatrics and 7.2% in surgery. In the first year, 1731 children were assessed as an emergency of whom 658 did not require admission to the inpatient ward. Midnight occupancy fell 17.7% in paediatrics and 25.4% in surgery. The nurse staffing costs fell over Pounds 32,000 in the first year. No adverse events occurred during the first year of operation; this type of facility could lead to a more efficient use of resources in any children's unit.

Bed Occupancy↗
PubMed1997

Quantitative structure-activity relationships (QSARs) for estrogen binding to the estrogen receptor: predictions across species.

The recognition of adverse effects due to environmental endocrine disruptors in humans and wildlife has focused attention on the need for predictive tools to select the most likely estrogenic chemicals from a very large number of chemicals for subsequent screening and/or testing for potential environmental toxicity. A three-dimensional quantitative structure-activity relationship (QSAR) model using comparative molecular field analysis (CoMFA) was constructed based on relative binding affinity (RBA) data from an estrogen receptor (ER) binding assay using calf uterine cytosol. The model demonstrated significant correlation of the calculated steric and electrostatic fields with RBA and yielded predictions that agreed well with experimental values over the entire range of RBA values. Analysis of the CoMFA three-dimensional contour plots revealed a consistent picture of the structural features that are largely responsible for the observed variations in RBA. Importantly, we established a correlation between the predicted RBA values for calf ER and their actual RBA values for human ER. These findings suggest a means to begin to construct a more comprehensive estrogen knowledge base by combining RBA assay data from multiple species in 3D-QSAR based predictive models, which could then be used to screen untested chemicals for their potential to bind to the ER. Another QSAR model was developed based on classical physicochemical descriptors generated using the CODESSA (Comprehensive Descriptors for Structural and Statistical Analysis) program. The predictive ability of the CoMFA model was superior to the corresponding CODESSA model.

Environmental Exposure↗
PubMed1994

The Sleep Disorders Questionnaire. I: Creation and multivariate structure of SDQ.

The development of the Sleep Disorders Questionnaire (SDQ) from the Sleep Questionnaire and Assessment of Wakefulness (SQAW) of Stanford University is described in detail. The extraction of the best question items from the SQAW and their subsequent rewording in the SDQ to insure greater completion rates are described. Two item test-retest reliability studies are reported on 71 controls and on 130 sleep-disorder patients, which confirmed adequate reliability. To create multivariate scoring scales, SDQ was then given in a multicenter study to 519 persons, 435 of whom were sleep-disorder patients with full polysomnography. Canonical Discriminant Function Analysis was employed, which resulted in four clinical-diagnostic scales: SA for sleep apnea, NAR for narcolepsy, PSY for psychiatric sleep disorder and PLM for periodic limb movement disorder. Each was adjusted for male and female responses and transformed to a percentile using the observed distribution of raw scores. Using Receiver Operating Characteristics analysis, cutoff points were determined for each scale to maximize its sensitivity and specificity. Positive and negative predictive values were also calculated. The SA and NAR scales proved to be the most discriminating.

Adult↗
PubMed1991

Inter-rater reliability for scoring periodic leg movements in sleep.

This study investigated inter-rater reliability for scoring periodic leg movements in sleep (PLMS) and related phenomena. Five highly experienced polysomnographic technologists each scored 24 nocturnal polysomnograms, the majority of which contained an appreciable number of PLMS. Results indicated high inter-rater reliability for some variables but more modest reliability for others. We discuss these findings in terms of efforts of standardization in polysomnographic scoring of sleep disorders.

Aged↗
PubMed1987

The assessment of a new technology for evaluating respiratory abnormalities in sleep.

This study assessed the diagnostic utility of two technologies for evaluating respiratory abnormalities in sleep. We compared conventional polysomnography with a new, ambulatory microprocessor technology. Two key features of the comparison involved: (a) the use of multiple, skilled interpreters of each system; and (b) inter-rater agreement within the systems as a crucial test for the diagnostic utility of each. Results indicated that general categories of respiratory abnormalities could be judged more reliably than more specific categories, regardless of technology. For certain categories of respiratory abnormalities, however, inter-rater agreement with the newer technology was extremely low (e.g., reliability coefficients of .12, .09, and -0.6). Factors contributing to these low diagnostic reliabilities are discussed. Our data indicate that any assessment of new technology cannot be made apart from the clinical judgments to be rendered with that new technology. This approach may be generalizable to the assessment of other diagnostic technologies.

Diagnosis, Computer-Assisted↗