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J O'Keefe

Publications and source records attributed to J O'Keefe.

At least 37 records · Page 2Linked to original sources
PubMed1999

Long-term outcome after primary angioplasty: report from the primary angioplasty in myocardial infarction (PAMI-I) trial.

OBJECTIVES: This study sought to compare the two-year outcome after primary percutaneous coronary angioplasty or thrombolytic therapy for acute myocardial infarction. BACKGROUND: Primary angioplasty, that is, angioplasty without antecedent thrombolytic therapy, has been shown to be an effective reperfusion modality for patients suffering an acute myocardial infarction. This report reviews the two-year clinical outcome of patients randomized in the Primary Angioplasty in Myocardial Infarction trial. METHODS: At 12 clinical centers, 395 patients who presented within 12 h of the onset of myocardial infarction were randomized to undergo primary angioplasty (195 patients) or to receive tissue-type plasminogen activator (t-PA) (200 patients) followed by conservative care. Patients were followed by physician visits, phone call, letter and review of hospital records for any hospital admission at one month, six months, one year and two years. RESULTS: At two years, patients undergoing primary angioplasty had less recurrent ischemia (36.4% vs. 48% for t-PA, p = 0.026), lower reintervention rates (27.2% vs. 46.5% for t-PA, p < 0.0001) and reduced hospital readmission rates (58.5% vs. 69.0% for t-PA, p = 0.035). The combined end point of death or reinfarction was 14.9% for angioplasty versus 23% for t-PA, p = 0.034. Multivariate analysis found angioplasty to be independently predictive of a reduction in death, reinfarction or target vessel revascularization (p = 0.0001). CONCLUSIONS: The initial benefit of primary angioplasty performed by experienced operators is maintained over a two-year follow-up period with improved infarct-free survival and reduced rate of reintervention.

Angioplasty, Balloon, Coronary↗
PubMed1999

Human spatial navigation: cognitive maps, sexual dimorphism, and neural substrates.

Recent research on navigation has been particularly notable for the increased understanding of the factors affecting human navigation and the neural networks supporting it. The use of virtual reality environments has made it possible to explore the effect of environment layout and content on way-finding performance, and it has shown that these effects may interact with the sex and age of subjects. Functional brain imaging, combined with the use of virtual environments, has revealed strong parallels between humans and other animals in the neural basis of navigation.

Aging↗
PubMed1999

I know where I stand!

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Place cells, navigational accuracy, and the human hippocampus.

The hippocampal formation in both rats and humans is involved in spatial navigation. In the rat, cells coding for places, directions, and speed of movement have been recorded from the hippocampus proper and/or the neighbouring subicular complex. Place fields of a group of the hippocampal pyramidal cells cover the surface of an environment but do not appear to do so in any systematic fashion. That is, there is no topographical relation between the anatomical location of the cells within the hippocampus and the place fields of these cells in an environment. Recent work shows that place cells are responding to the summation of two or more Gaussian curves, each of which is fixed at a given distance to two or more walls in the environment. The walls themselves are probably identified by their allocentric direction relative to the rat and this information may be provided by the head direction cells. The right human hippocampus retains its role in spatial mapping as demonstrated by its activation during accurate navigation in imagined and virtual reality environments. In addition, it may have taken on wider memory functions, perhaps by the incorporation of a linear time tag which allows for the storage of the times of visits to particular locations. This extended system would serve as the basis for a spatio-temporal event or episodic memory system.

Animals↗
PubMed1998

Knowing where and getting there: a human navigation network.

The neural basis of navigation by humans was investigated with functional neuroimaging of brain activity during navigation in a familiar, yet complex virtual reality town. Activation of the right hippocampus was strongly associated with knowing accurately where places were located and navigating accurately between them. Getting to those places quickly was strongly associated with activation of the right caudate nucleus. These two right-side brain structures function in the context of associated activity in right inferior parietal and bilateral medial parietal regions that support egocentric movement through the virtual town, and activity in other left-side regions (hippocampus, frontal cortex) probably involved in nonspatial aspects of navigation. These findings outline a network of brain areas that support navigation in humans and link the functions of these regions to physiological observations in other mammals.

Brain Mapping↗
PubMed1998

Place field dynamics and directionality in a spatial memory task.

In previous studies place fields have been shown to be governed by one or more polarizing stimuli such that rotation of the stimuli caused concomitant rotation of the fields. Place fields have also been observed to persist after removal of stimulus cues. In the present study we confirm the previous findings and report two new responses. Hippocampal place fields were observed to decrease or cease place specific firing after the removal of the polarizing cues. Others increased or initiated place specific firing after cue removal. Thus in these instances place field location was dependent on the orientation of the polarizing cues but place field magnitude was governed by their presence or absence. A subset of the place fields recorded in the present study were found to display directionality. Place field directionality was found to be governed by the polarizing cues such that cue rotation produced concomitant rotation in the direction of maximal firing. However directionally specific firing was unaffected by cue removal. These results suggest that place field directionality is initially set up by the polarizing cues but is subsequently independent of them.

Action Potentials↗
PubMed1998

The rhythmicity of cells of the medial septum/diagonal band of Broca in the awake freely moving rat: relationships with behaviour and hippocampal theta.

Chronic extracellular recordings were obtained from cells of the medial septum and diagonal band of Broca in rats performing a simple behavioural task. The cells were found to display a variety of bursting patterns phase-locked to hippocampal theta rhythm to a greater or lesser degree. Among phase-locked cells, no systematic distribution in preferential phase could be found, and these cells were shown to maintain their preferential phase for extended periods. Cells were classified into those which showed signs of a broadening of the repolarization phase of their action potential ('inflected': putative cholinergic) and those without ('non-inflected': putative GABAergic). Non-inflected cells tended to fire rhythmic bursts while inflected cells mostly fired in an irregular fashion, although still significantly phase-locked to hippocampal theta. In neither population did the phase-locked cells show any coherent distribution of their preferential phase. Sixty-five per cent of the rhythmically bursting cells showed a significant correlation between the interburst frequency and the animal's running speed. Five cells displayed rhythmic activity only when the rat ran in a specific direction. These results have implications for models of septohippocampal function and the effects of variable septal rhythmicity on the production of hippocampal theta rhythm.

Animals↗
PubMed1998

Knowing where things are parahippocampal involvement in encoding object locations in virtual large-scale space.

The involvement of the medial temporal-lobe region in allocentric mapping of the environment has been observed in human lesion and functional imaging work. Cognitive models of environmental learning ascribe a key role to salient landmarks in representing large-scale space. In the present experiments we examined the neural substrates of the topographical memory acquisition process when environmental landmarks were more specifically identifiable. Using positron emission tomography (PET), we measured regional cerebral blood flow changes while normal subjects explored and learned in a virtual reality environment. One experiment involved an environment containing salient objects and textures that could be used to discriminate different rooms. Another experiment involved a plain empty environment in which rooms were distinguishable only by their shape. Learning in both cases activated a network of bilateral occipital, medial parietal, and occipitotemporal regions. The presence of salient objects and textures in an environment additionally resulted in increased activity in the right parahippocampal gyrus. This region was not activated during exploration of the empty environment. These findings suggest that encoding of salient objects into a representation of large-scale space is a critical factor in instigating parahippocampal involvement in topographical memory formation in humans and accords with previous studies implicating parahippocampal areas in the encoding of object location.

Adult↗
PubMed1997

Robotic and neuronal simulation of the hippocampus and rat navigation.

The properties of hippocampal place cells are reviewed, with particular attention to the nature of the internal and external signals that support their firing. A neuronal simulation of the firing of place cells in open-field environments of varying shape is presented. This simulation is coupled with an existing model of how place-cell firing can be used to drive navigation, and is tested by implementation as a miniature mobile robot. The sensors on the robot provide visual, odometric and short-range proximity data, which are combined to estimate the distance of the walls of the enclosure from the robot and the robot's current heading direction. These inputs drive the hippocampal simulation, in which the robot's location is represented as the firing of place cells. If a goal location is encountered, learning occurs in connections from the concurrently active place cells to a set of 'goal cells', which guide subsequent navigation, allowing the robot to return to an unmarked location. The system shows good agreement with actual place-cell firing, and makes predictions regarding the firing of cells in the subiculum, the effect of blocking long-term synaptic changes, and the locus of search of rats after deformation of their environment.

Animals↗
PubMed1997

Analysis of the relative costs and effectiveness of primary angioplasty versus tissue-type plasminogen activator: the Primary Angioplasty in Myocardial Infarction (PAMI) trial. The PAMI Trial Investigators.

OBJECTIVES: We sought to determine the relative cost and effectiveness of two different reperfusion modalities in patients with acute myocardial infarction (AMI). BACKGROUND: Recent studies have found superior clinical outcomes after reperfusion by primary percutaneous transluminal coronary angioplasty (PTCA) compared with thrombolytic therapy. The high up-front costs of cardiac catheterization may diminish the relative advantages of this invasive strategy. METHODS: Detailed in-hospital charge data were available from all 358 patients with AMI randomized to tissue-type plasminogen activator (t-PA) or primary PTCA in the United States from the Primary Angioplasty in Myocardial Infarction trial. Resource consumption during late follow-up was estimated by assessment of major clinical events and functional status. RESULTS: Compared with t-PA, primary PTCA resulted in reduced rates of in-hospital mortality (2.3% vs. 7.2%, p = 0.03), reinfarction (2.8% vs. 7.2%, p = 0.06), recurrent ischemia (11.3% vs. 28.7%, p < 0.0001) and stroke (0% vs. 3.9%, p = 0.02) and a shorter hospital stay (7.6 +/- 3.3 days vs. 8.4 +/- 4.7 days, p = 0.04). Despite the initial costs of cardiac catheterization in all patients with the invasive strategy, total mean (+/- SD) hospital charges were $3,436 lower per patient with PTCA than with t-PA ($23,468 +/- $13,410 vs. $26,904 +/- $18,246, p = 0.04), primarily due to the reduction in adverse in-hospital outcomes. However, professional fees were higher after primary PTCA ($4,185 +/- $3,183 vs. $3,322 +/- $2,728, p = 0.001), and thus total charges, although favoring PTCA, were not significantly different ($27,653 +/- $13,709 vs. $30,227 +/- 18,903, p = 0.21). At a mean follow-up time of 2.1 +/- 0.7 years, no major differences in postdischarge events or New York Heart Association functional class were present between PTCA- and t-PA-treated patients, suggesting similar late resource consumption. Including in-hospital events, 83% of PTCA-treated patients were alive and free of reinfarction at late follow-up, compared with 74% of t-PA-treated patients (p = 0.06). CONCLUSIONS: Compared with t-PA, reperfusion by primary PTCA improves clinical outcomes with similar or reduced costs. These findings have important clinical implications in an increasingly cost-conscious health care environment.

Aged↗
PubMed1996

Influence of acute myocardial infarction location on in-hospital and late outcome after primary percutaneous transluminal coronary angioplasty versus tissue plasminogen activator therapy.

In the Primary Angioplasty in Myocardial Infarction trial, 395 patients with acute myocardial infarction (AMI) were prospectively randomized to tissue plasminogen activator (tPA) or primary percutaneous transluminal coronary angioplasty (PTCA). In 138 patients with anterior wall AMI, in-hospital mortality was significantly reduced by treatment with PTCA compared with tPA (1.4% vs 11.9%, p = 0.01). PTCA also resulted in lower rates of death or reinfarction (1.4% vs 18.0%, p = 0.0009), recurrent myocardial ischemia (11.3% vs 28.4%, p = 0.01), and stroke (0.0% vs 6.0%, p = 0.037) in anterior wall AMI. The independent beneficial effect of treatment with primary PTCA rather than tPA in anterior wall AMI was confirmed by multivariate analysis and interaction testing. The in-hospital mortality of 257 patients with nonanterior wall AMI was similar after PTCA and tPA (3.2% vs 3.8%, p = 0.82). Compared with tPA, however, primary PTCA resulted in a markedly lower rate of recurrent myocardial ischemia (9.7% vs 27.8%, p = 0.0002), fewer unscheduled catheterization and revascularization procedures, and a shorter hospital stay (7.0 vs 8.6 days, p = 0.01) in nonanterior wall AMI. Thus, compared with tPA, primary PTCA in patients with anterior wall AMI results in significantly improved survival, with lower rates of stroke, reinfarction, and recurrent myocardial ischemia. In nonanterior wall AMI, treatment with PTCA and tPA results in similar early mortality, although PTCA-treated patients have a more stable hospital course characterized by reduced recurrent ischemia, fewer subsequent invasive procedures, and earlier discharge.

Angioplasty, Balloon, Coronary↗