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R Baker

Publications and source records attributed to R Baker.

At least 37 records · Page 2Linked to original sources
PubMed1997

Characterization of Purkinje cells in the goldfish cerebellum during eye movement and adaptive modification of the vestibulo-ocular reflex.

The discharge characteristics of Purkinje cells were analyzed in the goldfish cerebellum during eye movement and adaptation of the vestibulo-ocular reflex (VOR). Purkinje cells, identified by the simultaneous recording of complex and simple spikes, were recorded in the cerebellar area where electrical microstimulation elicited ipsiversive horizontal eye movements. Simple spikes of Purkinje cells displayed signals related to head and/or eye velocity as determined independently during either VOR suppression or optokinetic stimulation, respectively. Head velocity-only Purkinje cells (12%) increased their firing rate in relationship to ipsilateral head movements. Two types of eye velocity-only Purkinje cells (28%) were found that responded either in phase with ipsi- (16%) or contralateral (12%) eye movement, respectively. Purkinje cells combining both eye and head velocity (60%) were classified into two groups according to their preferred direction for eye movement. Eye velocity signals either added to (18%) or subtracted from (42%) head velocity during all visuo-vestibular interactions. Short term adaptive changes of the VOR were induced by oscillating goldfish in a moving visual surround that modified the ratio of eye to head velocity (gain) from a level of 1.0 (16 degrees/s) towards gains ranging from 2.5 (40 degrees/s) to -1.0 (-16 degrees/s). Simple spike modulation of individual Purkinje cells was shown to correlate well with VOR performance throughout adaptation irrespective of training direction. Purkinje cell behavior always equaled the algebraic summation of eye and head velocity signal sensitivity. Causality of signal generation was addressed by measuring Purkinje cell responses to both eye and head velocity separately throughout the time course of VOR adaptation. The sensitivity of each type of Purkinje cell was found to be independent of the VOR gain state. We therefore conclude that the changes responsible for short term VOR plasticity do not occur in the cerebellum. These observations suggest that Purkinje cells integrate corollary head and eye velocity signals to continuously adjust the set point of brainstem VOR interneurons that embrace the substantive site for adaptive plasticity.

Acclimatization↗
PubMed1997

Neutrophil CD11B expression and neutrophil activation in pre-eclampsia.

1. Neutrophil activation was examined in 22 women with pre-eclampsia and 22 age- and gestation-matched control subjects using whole-blood flow cytometry to assess basal and platelet-activating factor stimulated CD11b and CD18. 2. Basal neutrophil CD11b expression was significantly increased in women with pre-eclampsia compared with normal pregnancy before delivery. A similar non-significant trend for CD18 was also observed. 3. Before delivery, neutrophil CD11b expression increased in a dose-dependent fashion after platelet-activating factor stimulation, with the differences between the groups maintained. A similar dose-dependent increase in CD18 expression was observed after platelet-activating factor. 4. There were no between-group differences in expression of either CD11b or CD18 at either 6 weeks or 6 months post partum, either before or after platelet-activating factor stimulation. 5. Neutrophil CD11b was positively correlated with plasma uric acid (r = 0.44, P = 0.04) in women with pre-eclampsia, suggesting that the extent of neutrophil activation correlates with disease severity. 6. An increase in basal neutrophil CD11b expression in women with pre-eclampsia is likely to be an index of neutrophil activation in vivo. Neutrophil release of free radicals and proteases may then help perpetuate a vicious cycle of endothelial and vascular dysfunction in the placental and systemic circulations. The cause of this activation is not known but could involve platelet activation, increased production of endothelin-1 or release of cytokines. Further studies will be required to elucidate the consequences of neutrophil activation in pre-eclampsia.

Adult↗
PubMed1997

Is ownership more important than the scientific credibility of audit protocols? A survey of medical audit advisory groups.

BACKGROUND: It is commonly accepted that ownership is an important factor in determining the acceptability and use of protocols or guidelines. OBJECTIVES: We aimed to determine whether Medical Audit Advisory Groups (MAAGs) are prepared to accept and use audit protocols developed systematically by an external agency. METHOD: A postal questionnaire was sent to all 105 MAAG chairmen in England and Wales to seek their views on the external development of protocols, the inclusion of evidence-based prioritized criteria, the general design of the protocols issued by the Lilly Audit Centre and the numbers of practices reported by MAAGs as making use of at least one of the first four protocols issued. RESULTS: Ninety-five MAAGs (90%) responded. Of these, 86% were in favour of the external development of protocols, and 98% and 94%, respectively, found evidence-based and prioritized criteria valuable; 98% felt the overall design and content of the Audit Centre protocols were excellent or good. A total of 1018 practices was known to have made use of one of these protocols, 261 taking part in multi-practice audits organized by their MAAGs. CONCLUSION: Ownership is not necessarily more important than scientific credibility and/or perceived utility. Externally developed audit protocols containing evidence-based, prioritized review criteria are acceptable to MAAGs, which are prepared to recommend their use in practice. Accordingly, such systematically developed protocols offer a promising and practical method for improving clinical effectiveness. Further research is needed, however, to determine the comparative impact on standards of care of protocols and other methods such as clinical guidelines.

Attitude of Health Personnel↗
PubMed1997

Clinical guidelines: where next?

In a growing number of countries, guidelines are playing an increasingly important role in assuring the quality of care. Their validity depends on a systematic development process and explicit links between recommendations and underlying evidence. Their role in aiding clinical decision making depends on their developers identifying the key decisions and their consequences; gathering the relevant evidence on the risks and costs of alternative decisions; and presenting the appropriate evidence to make each key decision in a simple and accessible format, possibly electronic. Decision analysis is a potentially powerful tool for clarifying clinical decisions and involving patients directly in the process but its routine use in guidelines is complex and has yet to be fully evaluated. Duplication of guidelines can be avoided by appraising and adapting existing guidelines in local contexts. There is very little evidence available about the impact of guidelines on the doctor-patient relationship. They might have a potentially deleterious effect, but the combination of explicit guidelines eliciting patient preferences and information technology might redress the balance by increasing the role of patients themselves.

Decision Support Techniques↗
PubMed1997

Ethanol endovascular management of brain arteriovenous malformations: initial results.

OBJECTIVE: The goal was to determine the safety and efficacy of absolute ethyl alcohol treatment in the management of intra-axial brain arteriovenous malformations (AVMs). METHODS: Seventeen patients (eight female and nine male patients; mean age, 41 yr) underwent ethanol endovascular therapy for treatment of their brain AVMs. Superselective amytal testing preceded all procedures. Neuroleptic intravenous anesthesia was used for 16 patients, and general anesthesia was used for 1 patient. Follow-up monitoring consisted of clinical evaluations, magnetic resonance imaging, and arteriography. RESULTS: In follow-up evaluations (mean follow-up period, 13 mo) after embolization of brain AVMs, neither vascular recanalization nor the neovascular recruitment phenomenon was observed in any patient. Progressive AVM thrombosis at arteriographic follow-up evaluation was a constant feature. Seven patients were cured of their AVMs with ethanol endovascular therapy alone. Three patients were cured of their lesions with ethanol embolization plus surgical resection. One patient was cured of his lesion with ethanol embolization and radiation therapy of the residual nidus. Three patients underwent only partial therapy, with significant improvement in symptoms. Three patients are currently undergoing ethanol endovascular therapy. Complications occurred with 8 of 17 patients, most of which were transient. Two patients died because of late subarachnoid hemorrhages, one patient 4 months and one patient 14 months after partial therapy. CONCLUSION: Progressive and permanent AVM occlusion is a common finding in arteriographic follow-up evaluations. In no patients did arterial recanalization or the neovascular recruitment phenomenon occur. Our initial results indicate that ethanol has a permanence that is seldom encountered with other embolic agents. With aggressive decadron therapy, the complications related to swelling in the brain are largely reversible.

Adult↗
PubMed1997

Normal and adapted visuooculomotor reflexes in goldfish.

Under normal physiological conditions, whole field visual motion generally occurs in response to either active or passive self-motion. In the laboratory, selective movement of the visual surround produces an optokinetic response (OKR) that acts primarily to support the vestibuloocular reflex (VOR). During visual world motion, however, the OKR can be viewed as operating independently over frequency and amplitude ranges insufficient for vestibular activation. The goal of the present study was to characterize this isolated behavior of the OKR in goldfish as an essential step for studying central neuronal correlates of visual-vestibular interactions and the mechanisms underlying oculomotor adaptation. After presentation of either binocular sinusoidal or step visual stimuli, conjugate eye movements were elicited with an amplitude and phase profile similar to that of other vertebrates. An early and a delayed component were measured with different dynamics that could be altered independently by visual training. The ensuing visuomotor plasticity was robust and exhibited five major characteristics. First, the gain of both early and delayed components of the OKR increased > 100%. Second, eye velocity decreased 0.5-2.0 s before the change in direction of stimulus velocity. Third, on lengthening the duration of a constant velocity visual stimulus (e.g., from 8 to 16 s), eye velocity decreased toward 0 degrees/s. This behavior was correlated with the direction and period as opposed to the frequency of the visual stimulus ("period tuning"). Fourth, visual stimulus training increased VOR eye velocity with a ratio of 0.6 to 1 to that measured for the OKR. Fifth, the OKR adaptation, eye velocity consistently oscillated in a conjugate, symmetrical fashion at 2.4 Hz in the light, whereas in the dark, a rhythmical low-amplitude eye velocity occurred at the visual training frequency. We conclude that the frequency and amplitude of visual stimuli for eliciting the goldfish OKR are well suited for complementing the VOR. Unlike most mammals, OKR adaptive modifications significantly alter VOR gain, whereas the effects of VOR training are much less on OKR gain. These observations suggest that both distributed circuits and discrete neuronal populations control visuo- and vestibulomotor performance. Finally, the existence of a rhythmic, "period tuned" visuomotor behavior provides a unique opportunity to examine the neuronal mechanisms of adaptive plasticity.

Animals↗
PubMed1997

Excitatory and inhibitory vestibular pathways to the extraocular motor nuclei in goldfish.

Electrophysiological, ultrastructural, and immunohistochemical techniques were utilized to describe the excitatory and inhibitory vestibular innervation of extraocular motor nuclei in the goldfish. In antidromically activated oculomotor motoneurons, electrical stimulation of the intact contralateral vestibular nerve produced short-latency, variable amplitude electrotonic excitatory postsynaptic potentials (EPSPs) at 0.5-0.7 ms followed by chemical EPSPs at 1.0-1.3 ms. Stimulation of the ipsilateral vestibular nerve produced small amplitude membrane hyperpolarizations at a latency of 1.3-1.7 ms in which equilibrium potentials were slightly more negative than resting potentials. The inhibitory postsynaptic potentials (IPSPs) reversed with large amplitudes after the injection of chloride ions suggesting a proximal soma-dendritic location of terminals exhibiting high efficacy inhibitory synaptic conductances. In antidromically identified abducens motoneurons and putative internuclear neurons, electrical stimulation of the contralateral vestibular nerve produced large-amplitude, short-latency electrotonic EPSPs at 0.5 ms followed by chemical depolarizations at 1.2-1.3 ms. Stimulation of the ipsilateral vestibular nerve evoked IPSPs at 1.4 ms that were reversed after injection of current and/or chloride ions. gamma-Aminobutyric acid (GABA) antibodies labeled inhibitory neurons in vestibular subdivisions with axons projecting into the ipsilateral medial longitudinal fasciculus (MLF). Putative GABAergic terminals surrounded oculomotor, but not abducens, motoneurons retrogradely labeled with horseradish peroxidase. Hence the spatial distribution of GABAergic neurons and terminals appears highly similar in the vestibuloocular system of goldfish and mammals. Electron microscopy of motoneurons in the oculomotor and abducens nucleus showed axosomatic and axodendritic synaptic endings containing spheroidal synaptic vesicles establishing chemical, presumed excitatory, synaptic contacts with asymmetric pre- and/or postsynaptic membrane specializations. The majority of contacts with spheroidal vesicles displayed gap junctions in which the chemical and electrotonic synapses were either en face to dissimilar or adjacent to one another on the same soma/dendritic profiles. Another separate set of axosomatic synaptic endings, presumed to be inhibitory, contained pleiomorphic synaptic vesicles with symmetric pre- and/or postsynaptic membrane specializations that never included gap junctions. Excitatory and inhibitory synaptic contacts appeared equal in number but were more sparsely distributed along the soma-dendritic profiles of oculomotor as compared with abducens motoneurons. Collectively these data provide evidence for both disynaptic vestibular inhibition and excitation in all subdivisions of the extraocular motor nuclei suggesting the basic vestibulooculomotor blueprint to be conserved among vertebrates. We propose that unique vestibular neurons, transmitters, pathways, and synaptic arborizations are homologous structural traits that have been essentially preserved throughout vertebrate phylogeny by a shared developmental plan.

Abducens Nerve↗
PubMed1997

Phenotypic specification of hindbrain rhombomeres and the origins of rhythmic circuits in vertebrates.

This essay considers the ontogeny and phylogeny of the cranial neural circuitry producing rhythmic behaviors in vertebrates. These behaviors are characterized by predictable temporal patterns established by a neuronal network variously referred to as either a pacemaker, neural oscillator or central pattern generator. Comparative vertebrate studies have demonstrated that the embryonic hindbrain is divided into segmented compartments called rhombomeres, each of which gives rise to a distinct complement of cranial motoneurons and, as yet, unidentified populations of interneurons. We now propose that novel rhythmic circuits were innovations associated with the adoption of cardiac and respiratory pumps during the protochordate-vertebrate transition. We further suggest that the pattern-generating circuits of more recent innovations, such as the vocal, electromotor and extraocular systems, have originated from the same Hox gene-specified compartments of the embryonic hindbrain (rhombomeres 7-8) that gave rise to rhythmically active cardiac and respiratory circuits. Lastly, we propose that the capability for pattern generation by neurons originating from rhombomeres 7 and 8 is due to their electroresponsive properties producing pacemaker oscillations, as best typified by the inferior olive which also has origins from these same hindbrain compartments and has been suggested to establish rhythmic oscillations coupled to sensorimotor function throughout the neuraxis of vertebrates.

Animals↗
PubMed1997

Will the future GP remain a personal doctor?

During the past three decades, general practice has evolved into a form of primary health care that provides a wide range of reactive, anticipatory, and preventive services, and now also purchases secondary care. As a result, practices now have more staff and more complex patterns of organization. However, most patients prefer smaller practices and personal list systems. There is a danger that a core feature of general practice--personal care--is gradually being eroded. If this trend is to be halted, the organization of general practices and the support available to them must be revised so that they can continue to provide personal care, yet also offer a wide range of effective services in the community.

Continuity of Patient Care↗
PubMed1997

Effective audit in general practice: a method for systematically developing audit protocols containing evidence-based review criteria.

Though many general practitioners (GPs) now take part in audit, there is still concern about the extent to which participation in audit leads to improvements in practice. Improved methods are needed for the incorporation of research evidence into criteria for use in audit. In this paper, a six-stage systematic method is described for developing audit protocols containing prioritized evidence-based criteria. The stages are: selection of a topic, identification of key elements of care, focused literature reviews, prioritization of the criteria on the strength of the evidence and impact on outcome, preparation of full documentation, and peer review.

Clinical Protocols↗
PubMed1997

Synovial tissues collected from rheumatoid patients undergoing total joint arthroplasty express markers for acute inflammation.

Rheumatoid arthritis is an autoimmune disease that causes inflammation mainly in synovial tissues. RA manifests as a chronic polyarthritis with intermittent acute inflammatory episodes. The inflammatory sites are characterized by infiltration of activated lymphocytes and macrophages into the synovial membrane, and the proliferation of synovial cells. The local production of a number of cytokines by proliferative synovial cells as well as by infiltrating cells appears to account for many of the pathological and clinical manifestations in rheumatoid arthritis. Tissues were collected from twelve RA patients undergoing joint replacement surgery. The synovium was collected and the cell types were identified, and markers for chronic and acute inflammatory mediators were measured. The cells types found in the synovium are capable of secreting cytokines which are capable of both acute inflammation (IL-1, IL-6, IL-8, MCP-1 and TNF), as well as chronic inflammation (IL-2, IL-10, and IL-4). The results obtained showed that the macrophages-derived acute inflammatory cytokines (IL-1, IL-6 and IL-8) were easily detected at levels of 22.6 +/- 12 pg/mg protein; 48.5 +/- 42 pg/mg protein, and 76 +/- 31 pg/mg protein; respectively. T-cell derived chronic inflammation cytokines (IL-2, IL-4 and IL-10) were rarely detected. Retrieved tissues that immunostained positive for IL-6, IL-1 and IL-8 also is suggestive of an acute inflammatory response. The results clearly demonstrate that the acute response may be responsible for the subsequent need for joint arthroplasties.

Acute Disease↗
PubMed1997

Scholarly error.

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Alcohol Drinking↗
PubMed1996

N-heteroaryl-2-phenyl-3-(benzyloxy)piperidines: a novel class of potent orally active human NK1 antagonists.

The preparation of a series of N-heteroarylpiperidine ether-based human NK1 antagonists is described. Two of the compounds 3-[-(2S,3S)-3-(((3,5-bis(trifluoromethyl)phenyl)methyl)oxy)- 2-phenylpiperidino}methyl]-1,2,4-triazole (11) and 5-[¿(2S,3S)-3-(((3,5-bis(trifluoromethyl)-phenyl)methyl)oxy)-2- phenylpiperidino}methyl]-3-oxo-1,2,4-triazolone (12)), in particular, are orally bioavailable and exhibited significant improvements in potency, both in vitro and in vivo, over the lead (carboxamidomethyl)piperidine ether 1. Rat liver microsome studies on a selected number of compounds from this series show the triazolone heterocycle to be considerably more stable than the others. Furthermore, both 11 and 12 have been profiled in a number of assays that may be predictive of the clinical utility of substance P antagonists.

Animals↗