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Biomedical subjects

Michael Rigby

Publications and source records attributed to Michael Rigby.

At least 19 recordsLinked to original sources
PubMed2006

A data-gathering broker as a future-orientated approach to supporting EPR users.

With the continued expansion of electronic patient record systems ahead of comprehensive evidence, metrics, or future-proofing, health informatics in Europe and beyond is embarking on a faith-driven adventure that also risks data swamping of end-users. An alternative approach is an information broker system, drawing from departmental data sources. A 3-year study in health and social care has produced a first demonstrator which can search for specified information in heterogeneous distributed data stores, with source-specific permission can copy it, and then merge the search results into one integrated picture in a real-time process which is also captured in an audit system. The research project has addressed a number of issues during the study, including updating the concepts of role-based access, semantic interoperability, and harnessing web-based services bound at the time of need. A demonstrator now exists, and provides a platform for further application and development research. This paper summarises how this opens up a viable alternative approach for the next generation of health record systems, enabling record searching and integration as and when it is needed for specific patient-related purposes, whilst being independent of organisations, diagnostic approaches, or service delivery structures, and reducing the risks of data swamping.

Access to Information↗
PubMed2006

N',2-diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists II.

Introduction of selected amine containing side chains into the 3-position of N',2-diphenylquinoline-4-carbohydrazide based NK3 antagonists abolishes unwanted hPXR activation. Introduction of a fluorine at the 8-position is necessary to minimize unwanted hI(Kr) affinity and a piperazine N-tert-butyl group is necessary for metabolic stability. The lead compound (8m) occupies receptors within the CNS following oral dosing (Occ(90) 7 mg/kg po; plasma Occ(90) 0.4 microM) and has good selectivity and excellent PK properties.

Administration, Oral↗
PubMed2006

N',2-diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists.

A new class of potent NK3R antagonists based on the N',2-diphenylquinoline-4-carbohydrazide core is described. In an ex vivo assay in gerbil, the lead compound 2g occupies receptors within the CNS following oral dosing (Occ(90) 30 mg/kg po; plasma Occ(90) 0.95 microM) and has good selectivity and promising PK properties.

Administration, Oral↗
PubMed2006

Pre-treatment with 3,4-methylenedioxymethamphetamine (MDMA) causes long-lasting changes in 5-HT2A receptor-mediated glucose utilization in the rat brain.

The current study examined the long-term effect of brief exposure to 3,4-methylenedioxymethamphetamine (MDMA) on local cerebral glucose utilization (LCGU) in specific brain regions immediately following administration of the 5-HT2A/2C receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Wistar rats (post-natal day (PND) 28, n = 24) were administered MDMA (5 mg/kg, i.p.) or saline (1 ml/kg, i.p.) four times daily for 2 consecutive days and core body temperature was recorded. Fifty-five days later and 10 min following injection of DOI (1 mg/kg, i.p.) or saline, LCGU was measured using the [14C]2-deoxyglucose (2-DG) technique. In the 4 hours following the initial injection (PND 28), MDMA-treated rats exhibited significant hyperthermia compared with saline-treated controls (p < 0.05-0.01). Eight weeks later, immediately following DOI challenge, LCGU was significantly elevated (an increase of 47%, p < 0.05) in the nucleus accumbens of MDMA/DOI pretreated rats, compared with that in MDMA/saline pre-treated controls. A similar trend was observed in other areas such as the lateral habenula, somatosensory cortex and hippocampal regions (percentage changes of 27-41%), but these did not reach significance. Blood glucose levels were significantly elevated in both groups of DOI-treated rats (p < 0.05-0.01). Thus, brief exposure of young rats to an MDMA regimen previously shown to cause anxiety-like behaviour and modest serotonergic neurotoxicity (Bull et al., 2004) increased DOI-induced energy metabolism in the nucleus accumbens and tended to increase metabolism in other brain regions, including the hippocampus, consistent with the induction of long-term brain region specific changes in synaptic plasticity.

Animals↗
PubMed2006

Ubiquitous technologies in health: new challenges of opportunity, expectation, and responsibility.

In spite of their name, 'ubiquitous' technologies are not yet ubiquitous in the true sense of the word, but rather are 'novel', being at the research, pilot, and selective use stages. In future, the proliferation in types of application, the major increase in cases and data volumes, and above all the dependence on ubiquitous technologies will raise practical, ethical, and liability issues. Equally significantly, it will require health service redesign, including new response services. Health informaticians need to be active in stimulating consideration of all these issues, as part of both social and professional responsibility.

Biomedical Technology↗
PubMed2005

Species differences in tachykinin receptor distribution: further evidence that the substance P (NK1) receptor predominates in human brain.

Marked species differences in the distribution of central tachykinin receptors are reported but uncertainty remains about the ability of available ligands to detect NK2 and NK3 receptors in human brain. We compared the distribution of NK1, NK2, and NK3 receptors in sections from rodent, primate, and human brain using the 125I-labeled ligands substance P (SP) for the NK1 receptor, neurokinin A (NKA) for the NK2 receptor, and neurokinin B (NKB) and eledoisin for NK3 receptors. Duration of exposure to autoradiographic film was from 7 days for [125I]SP up to 90 days for the other ligands. High levels of specific [125I]SP binding were seen throughout the brains of all species studied. Specific [125I]NKA binding was detected in brains from neonatal rat, and to a lesser level in adult rat, gerbil, and guinea pig; it was not detected in monkey or human brain, but was present in circular muscle of human duodenum, confirming that this ligand binds to human NK2 receptors under our experimental conditions. Specific [125I]NKB and [125I]eledoisin binding was widespread in brain sections from rats, gerbils, and guinea pigs, and very low levels were also detected in marmoset, squirrel monkey, and rhesus monkey brain after prolonged (up to 90 days) exposure. We failed to identify specific eledoisin binding in human brain, even after prolonged exposures. These findings demonstrate that the NK1 receptor is the predominant tachykinin receptor expressed in primate and human brain, but that low levels of NK3 receptor are present in nonhuman, primate brain.

Animals↗
PubMed2005

Essential prerequisites to the safe and effective widespread roll-out of e-working in healthcare.

Health informatics applications are advocated in many setting in many countries, with convincing logic as to their likely benefits. But at present these visions are being projected to rapid enforced implementation without the necessary foundations of: empirical evidence, beta piloting or replication studies, appreciation of the magnitude of change for health professionals and systems in electronic working compared to paper-based systems. This is creating legal and ethical risks that are largely avoidable, all for lack of post-piloting study and adequate evidence-based preparation. Instead, roll-out should be facilitated by developing good implementation practice based on empirical evidence from beta sites, to cover the following aspects: evidence, evaluation, equipment, education, empowerment. e-Working is an essential technology to support modern healthcare delivery. It needs to be as evidence-based as any other health care technology, but at present policy and parsimony are forcing it to fall short of these standards, thus generating unethical risks.

Diffusion of Innovation↗
PubMed2005

Principles and challenges of child health and safety indicators.

Indicators are an important tool for monitoring population health and service responses to population need. However, not only do they need to be empirically based, but they should measure those areas of most significance to the population group concerned. Their objective is to highlight areas needing attention, rather than to show individual detailed causes. The present paper reports key work in child health indicators and the challenges faced by those seeking to apply them to child safety and injury prevention.

Child↗
PubMed2005

Managing healthcare information: the role of the broker.

We describe a prototype information broker that has been developed to address typical healthcare information needs, using web services to obtain data from autonomous, heterogeneous sources. Some key features are reviewed: how data sources are turned into data services; how we enforce a distributed access control policy; and how semantic interoperability is achieved between the broker and its data services. Finally, we discuss the role that such a broker might have in a Grid context, as well as the limitations this reveals in current Grid provision.

Computer Systems↗
PubMed2005

The Data-Gathering Broker--A User-Based Approach to Viable EPR Systems.

With the continued expansion of Electronic Patient Record systems ahead of comprehensive evidence, metrics, or future-proofing, European health informatics is embarking on a faith-driven adventure that also risks data swamping of end-users. An alternative approach is an information broker system, drawing from departmental data sources. A three-year study in health and social care has produced a first demonstrator which can search for specified information in heterogeneous distributed data stores, with source-specific permission can copy it, and then merge the search results in a real-time process.

Electronic Health Records↗
PubMed2004

The ultrastructural localisation of the N-methyl-D-aspartate NR2B receptor subunit in rat lumbar spinal cord.

Glutamate together with its N-methyl-d-aspartate (NMDA) receptors has an important role in the transmission of stimuli in the spinal cord. Whilst the expression of the various NMDA receptor subunits within the spinal cord has been investigated the subcellular location of the NMDA NR2B subunit has yet to be definitively established. Both mRNA and light microscopical studies have failed to unequivocally demonstrate the proposed pre-synaptic location of this subunit. This has been proposed from pharmacological data and is thought to underlie the apparent analgesic properties of selective NR2B antagonists. Using pre-embedding immunohistochemistry combined with electron microscopy our findings provide the first definitive morphological evidence for both a pre- and post-synaptic localisation of NR2B/containing NMDA receptors, and suggest expression by astrocytes, in the rat lumbar spinal cord.

Animals↗
PubMed2004

Visions and strategies to improve evaluation of health information systems. Reflections and lessons based on the HIS-EVAL workshop in Innsbruck.

BACKGROUND: Health care is entering the Information Society. It is evident that the use of modern information and communication technology offers tremendous opportunities to improve health care. However, there are also hazards associated with information technology in health care. Evaluation is a means to assess the quality, value, effects and impacts of information technology and applications in the health care environment, to improve health information applications and to enable the emergence of an evidence-based health informatics profession and practice. OBJECTIVE: In order to identify and address the frequent problems of getting evaluation understood and recognised, to promote transdisciplinary exchange within evaluation research, and to promote European cooperation, the Exploratory Workshop on "New Approaches to the Systematic Evaluation of Health Information Systems" (HIS-EVAL) was organized by the University for Health Sciences, Medical Informatics and Technology (UMIT), Innsbruck, Austria, in April 2003 with sponsorship from the European Science Foundation (ESF). METHODS: The overall program was structured in three main parts: (a). discussion of problems and barriers to evaluation; (b). defining our visions and strategies with regard to evaluation of health information systems; and (c). organizing short-term and long-term activities to reach those visions and strategies. RESULTS: The workshop participants agreed on the Declaration of Innsbruck (see ), comprising four observations and 12 recommendations with regard to evaluation of health information systems. Future activities comprise European networking as well as the development of guidelines and standards for evaluation studies. CONCLUSION: The HIS-EVAL workshop was intended to be the starting point for setting up a network of European scientists working on evaluation of health information systems, to obtain synergy effects by combining the research traditions from different evaluation fields, leading to a new dimension and collaboration on further research on information systems' evaluation.

Education↗
PubMed2004

Protecting the patient by promoting end-user competence in health informatics systems-moves towards a generic health computer user "driving license".

The effectiveness and quality of health informatics systems' support to healthcare delivery are largely determined by two factors-the suitability of the system installed, and the competence of the users. However, the profile of users of large-scale clinical health systems is significantly different from the profile of end-users in other enterprises such as the finance sector, insurance, travel or retail sales. Work with a mental health provider in Ireland, who was introducing a customized electronic patient record (EPR) system, identified the strong legal and ethical importance of adequately skills for the health professionals and others, who would be the system users. The experience identified the need for a clear and comprehensive generic user qualification at a basic but robust level. The European computer driving license (ECDL) has gained wide recognition as a basic generic qualification for users of computer systems. However, health systems and data have a series of characteristics that differentiate them from other data systems. The logical conclusion was the recognition of a need for an additional domain-specific qualification-an "ECDL Health Supplement". Development of this is now being progressed.

Computer Literacy↗
PubMed2004

Neuroprotective effects of M826, a reversible caspase-3 inhibitor, in the rat malonate model of Huntington's disease.

1. Caspases, key enzymes in the apoptosis pathway, have been detected in the brain of HD patients and in animal models of the disease. In the present study, we investigated the neuroprotective properties of a new, reversible, caspase-3-specific inhibitor, M826 (3-([(2S)-2-[5-tert-butyl-3-[[(4-methyl-1,2,5-oxadiazol-3-yl)methyl]amino]-2-oxopyrazin-1(2H)-yl]butanoyl]amino)-5-[hexyl(methyl)amino]-4-oxopentanoic acid), in a rat malonate model of HD. 2. Pharmacokinetic and autoradiography studies after intrastriatal (i.str.) injection of 1.5 nmol of M826 or its tritiated analogue [(3)H]M826 indicated that the compound diffused within the entire striatum. The elimination half-life (T(1/2)) of M826 in the rat striatum was 3 h. 3. I.str. injection of 1.5 nmol of M826 10 min after malonate infusion induced a significant reduction (66%) in the number of neurones expressing active caspase-3 in the ipsilateral striatum. 4. Inhibition of active caspase-3 translated into a significant but moderate reduction (39%) of the lesion volume, and of cell death (24%), 24 h after injury. The efficacy of M826 at inhibiting cell death was comparable to that of the noncompetitive NMDA receptor antagonist MK801. 5. These data provide in vivo proof-of-concept of the neuroprotective effects of reversible caspase-3 inhibitors in a model of malonate-induced striatal injury in the adult rat.

Animals↗
PubMed2004

Improving governance and reducing risk in electronic patient record systems: ensuring appropriate competencies for support and end-user staff.

As clinical health information systems, particularly Electronic Patient Records, become widely used, so it is important to address the Governance and Risk Reduction policies needed to ensure their safe and effective use. Greater emphasis needs to be placed on ensuring that all staff involved have relevant, recognized competencies. This paper describes two initiatives--one for health informatics staff, and one for end-user health professionals--ensure and assess such competencies

Computer Literacy↗
PubMed2002

Substance P (neurokinin 1) receptor antagonists enhance dorsal raphe neuronal activity.

Substance P receptor [neurokinin 1 (NK1] antagonists (SPAs) represent a novel mechanistic approach to antidepressant therapy with comparable clinical efficacy to selective serotonin reuptake inhibitors (SSRIs). Because SSRIs are thought to exert their therapeutic effects by enhancing central serotonergic function, we have examined whether SPAs regulate neuronal activity in the dorsal raphe nucleus (DRN), the main source of serotonergic projections to the forebrain. Using in vivo electrophysiological techniques in the guinea pig, we found that administration of the highly selective NK1 receptor antagonist 1-(5-[[(2R,3S)-2-([(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]oxy)-3-(4-phenyl)morpholin-4-yl]methyl]-2H-1,2,3-triazol-4-yl)-N,N-dimethylmethanamine (L-760735) caused an increase in DRN neuronal firing rate. However, unlike chronic treatment with fluoxetine, there was no detectable 5-HT1A autoreceptor desensitization. In vitro electrophysiological investigation showed that these effects were not mediated by a direct action in the DRN, an observation supported by immunocytochemical analysis that identified the lateral habenula (LHb) as a more likely site of action. Subsequently, we found that local application of L-760735 into the LHb increased firing in the DRN, which, together with our data showing that L-760735 increased metabolic activity in the cingulate cortex, amygdala, LHb, and DRN, indicates that the effects of L-760735 may be mediated by disinhibition of forebrain structures acting via a habenulo raphe projection. These findings support other evidence for an antidepressant profile of SPAs and suggest that regulation of DRN neuronal activity may contribute to their antidepressant mechanism of action but in a manner that is distinct from monoamine reuptake inhibitors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗