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Biomedical subjects

D K Menon

Publications and source records attributed to D K Menon.

At least 37 records · Page 2Linked to original sources
PubMed2005

Deficits in decision-making in head injury survivors.

Many survivors of head injury suffer chronic personality changes, such as increased impulsivity and a lack of insight and poor judgment. These changes are well recognized and likely to affect the ability to make decisions. However, systematic investigations into their nature have been limited. This study aims to explore the nature of decision making in head injury survivors using a computerized task. Forty-three head injury survivors and a group of 29 matched controls completed the computerized task. The task required participants to make a probability-based choice and to further qualify this choice with an associated "bet." This betting component allows an assessment of the participant's level of confidence in the decision, via the affective evaluation of its possible consequences in terms of points won or lost. The survivors were found to be slow at making the probability- based choice. Whilst at highly favorable odds, the survivors chose the most likely option in a similar manner to the controls, they chose the most likely option less often than the controls at less favorable odds. Examination of the survivors' betting behavior revealed that they responded impulsively compared to controls. This pattern of prolonged decision making and poor quality of decisions is similar to that found in patients with orbitofrontal cortex lesions, whilst impulsive betting has been associated with abnormalities of the dopamine system. These complex deficits in decision making may contribute to difficulties with poor judgment and inhibition in head injury survivors.

Adolescent↗
PubMed2005

Modelling the impact of an influenza pandemic on critical care services in England.

The UK Influenza Pandemic Contingency Plan does not consider the impact of a pandemic on critical care services. We modelled the demand for critical care beds in England with software developed by the Centers for Disease Control (Flusurge 1.0), using a range of attack rates and pandemic durations. Using inputs that have been employed in UK Department of Health scenarios (25% attack rate and 8-week pandemic duration) resulted in a demand for ventilatory support that exceeded 200% of present capacity. Demand remained unsustainably high even when more favourable scenarios were considered. Current critical care bed capacity in England would be unable to cope with the increased demand provided by an influenza pandemic. Appropriate contingency planning is essential.

Bed Occupancy↗
PubMed2005

Neurometabolic coupling in the vegetative and minimally conscious states: preliminary findings.

The objective of this study was to determine the integrity of the homoeostatic coupling relationship between neuronal electrical function and cerebral metabolism in the vegetative and minimally conscious states. Ten patients who met recognised diagnostic criteria (six in the vegetative state and four minimally conscious) were investigated using simultaneous electroencephalography and positron emission tomography. It was found that the coupling between neuronal electrical activity and regional glucose metabolism was preserved in all the minimally conscious patients but was absent in all the vegetative state patients. Our preliminary results suggest patients in the vegetative state may endure an impaired coupling relation between neuronal electrical function and cerebral energy metabolism.

Adult↗
PubMed2004

Cognitive sequelae of head injury: involvement of basal forebrain and associated structures.

Traumatic brain injury is the most common cause of death and disability in young people and survivors often suffer from chronic cognitive deficits. From animal, post-mortem and cognitive studies, there is now increased evidence that abnormalities in the cholinergic system may be underlying some of these deficits. This study investigated this hypothesis in a group of survivors of moderate-severe head injury (n = 31). Patients completed a comprehensive neuropsychological assessment and an MRI scan. Compared with a group of controls (matched on age, sex and premorbid intelligence quotient), the patients showed deficits in sustained attention, paired associate learning and reaction time, but comparative preservation of spatial working memory. Voxel-based morphometry revealed reduced grey matter density in the head injured group in the basal forebrain, the hippocampal formation and regions of the neocortex. These cognitive and structural results are consistent with cholinergic dysfunction. These preliminary findings suggest that cholinergic enhancers may be an effective treatment of cognitive deficits post head injury.

Adult↗
PubMed2004

Ketamine disrupts frontal and hippocampal contribution to encoding and retrieval of episodic memory: an fMRI study.

The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine produces episodic memory deficits. We used functional magnetic resonance imaging to characterize the effects of ketamine on frontal and hippocampal responses to memory encoding and retrieval in healthy volunteers using a double-blind, placebo-controlled, randomized, within-subjects comparison of two doses of intravenous ketamine. Dissociation of the effects of ketamine on encoding and retrieval processes was achieved using two study-test cycles: in the first, items were encoded prior to drug infusion and retrieval tested, during scanning, on drug; in the second, encoding was scanned on drug, and retrieval tested once ketamine plasma levels had declined. We additionally determined the interaction of ketamine with the depth of processing that occurred at encoding. A number of effects upon task-dependent activations were seen. Overall, our results suggest that left frontal activation is augmented by ketamine when elaborative semantic processing is required at encoding. In addition, successful encoding on ketamine is supplemented by additional non-verbal processing that is incidental to task demands. The effects of ketamine at retrieval are consistent with impaired access to accompanying contextual features of studied items. Our findings show that, even when overt behaviour is unimpaired, ketamine has an impact upon the recruitment of key regions in episodic memory task performance.

Adolescent↗
PubMed2004

Cerebral neutrophil recruitment, histology, and outcome in acute ischemic stroke: an imaging-based study.

BACKGROUND AND PURPOSE: Evidence now exists for a pathogenic role for neutrophils in acute cerebral ischemia. We have studied the patterns and temporal profile of cerebral neutrophil recruitment to areas of acute ischemic stroke (IS) and have attempted to correlate this with neurological status and outcome. METHODS: Patients with cortical middle cerebral artery (MCA) IS were recruited within 24 hours of clinical onset. Neutrophil recruitment was studied using indium-111 (111In) troponolate-labeled neutrophils, planar imaging, and single-photon emission computed tomography (SPECT). Volume of brain infarction was calculated from concurrent computed tomography (CT). Hematoxylin and eosin sections were obtained postmortem (n=2). Outcome was measured using Barthel, Rankin, and National Institute of Health Stroke (NIHSS) scales. RESULTS: Fifteen patients were studied. Significant 111In-neutrophil recruitment to ipsilateral hemisphere, as measured by asymmetry index (AI), was demonstrated within 24 hours of onset in 9 patients; this response was heterogenous between patients and on repeated measurement attenuated over time. Histologically, recruitment was confirmed within intravascular, intramural, and intraparenchymal compartments. Interindividual heterogeneity in neutrophil response did not correlate with infarct volume or outcome. In an exploratory analysis, neutrophil accumulation appeared to correlate significantly with infarct expansion (Spearman rho=0.66; P=0.03, n=12). CONCLUSIONS: Neutrophils recruit to areas of ischemic brain within 24 hours of symptom onset. This recruitment attenuates over time and is confirmed histologically. While neutrophil accumulation may be associated with either the magnitude or the rate of infarct growth, these results require confirmation in future studies.

Brain Ischemia↗
PubMed2004

Evaluation of infusion pump performance in a magnetic resonance environment.

BACKGROUND AND OBJECTIVE: For use in a magnetic resonance (MR) scanning room infusion pumps must be MR safe and compatible. This study tested two commonly used infusion pumps (Alaris P6000 and Alaris Asena-GH) to determine if they met these criteria. METHODS: The pumps underwent testing within the scanning room of a 3 T MR scanner. Pump infusion rates were tested at up to 100 Gauss magnetic field strength, with and without radio frequency signals present. The effect of the pumps on image quality was assessed. The occlusion pressure alarm of the pumps was tested at up to 100 Gauss. The projectile risk was assessed by measuring the force exerted upon the pumps at the entrance to the scanner. RESULTS: The maximum mean flow rate errors at 100 Gauss were 2.18% for the Alaris P6000 and 1.42% for the Alaris Asena-GH, both within our accepted limits. Radio frequency signals had no effect on flow rate. The pumps produced no discernable artefacts on the acquired images. The maximum mean occlusion pressure error was 204 mmHg higher for the Alaris P6000 pump and 99 mmHg lower for the Alaris Asena-GH (P-values < 0.001) at 100 Gauss compared to testing outside the scanner. Both pumps were subject to significant attractive force at the entrance to the scanner. CONCLUSIONS: Whilst the pumps cannot strictly be termed MR safe or compatible at 100 Gauss we have demonstrated that flow rates are unchanged and that, for the Alaris Asena-GH, the effect on the occlusion pressure alarm is unlikely to have patient safety implications.

Equipment Design↗
PubMed2004

Acute ketamine administration alters the brain responses to executive demands in a verbal working memory task: an FMRI study.

We have used functional MRI to determine the effects of ketamine on brain systems activated in association with a working memory task. Healthy volunteers received intravenous infusions of placebo, ketamine at 50 ng/ml plasma concentration, and ketamine at 100 ng/ml. They were scanned while carrying out a verbal working memory task in which we varied the executive requirements (manipulation vs maintenance processes) and the mnemonic load (three vs five presented letters). We previously showed that ketamine produces a specific behavioral impairment in the manipulation task. In the current study, we modified tasks in order to match performance across drug and placebo conditions, and used an event-related fMRI design, allowing us to remove unsuccessful trials from the analysis. Our results suggest a task-specific effect of ketamine on working memory in a brain system comprising frontal cortex, parietal cortex, and putamen. When subjects are required to manipulate presented letters into alphabetical order, as opposed to maintaining them in the order in which they were presented, ketamine is associated with significantly greater activity in this system, even under these performance-matched conditions. No significant effect of ketamine was seen in association with increasing load. This suggests that our findings are not explicable in terms of a nonspecific effect of ketamine when task difficulty is increased. Rather, our findings provide evidence that the predominant effects of low, subdissociative doses of ketamine are upon the control processes engaged by the manipulation task. Furthermore, we have shown that ketamine's effects may be elucidated by fMRI even when overt behavioral measures show no evidence of impairment.

Adult↗
PubMed2004

Integrated approaches to academic anaesthesia - the Cambridge experience.

There is mounting concern about the pressures experienced by University Departments of Anaesthesia, which, if lost, could threaten undergraduate peri-operative medicine teaching, development of critical appraisal skills among anaesthetists, and the future of coherent research programs. We have addressed these problems by establishing a foundation course in scientific methods and research techniques (the Cambridge SMART Course), complemented by competitive, fully funded, 12-month academic trainee attachments. Research conducted during academic attachments has been published and used to underpin substantive grant applications allowing work towards higher degrees. Following the attachment, a flexible scheme ensures safe reintroduction to clinical training. Research at consultant level is facilitated by encouraging applications for Clinician Scientist Fellowships, and by ensuring that the University Department champions, legitimises and validates the allocation of research time within the new consultant contract. We believe that these are important steps in safeguarding research and teaching in anaesthesia, critical care and peri-operative medicine.

Anesthesiology↗
PubMed2003

Hyperoxia and the cerebral hemodynamic responses to moderate hyperventilation.

BACKGROUND: A reduction in the arterial partial pressure of CO2 (PaCO2) leads to a rapid reduction in cerebral blood flow (CBF). However, despite continuing hypocapnia there is secondary recovery of CBF over time as a result of increases in lactic acid production. Hyperoxia is thought to modulate the production of lactic acid. This study examined the kinetics of middle cerebral artery flow velocity (MCA FV) reduction during hyperventilation, and its modulation by hyperoxia. METHODS: Cerebral blood flow was assessed using transcranial Doppler ultrasound in nine healthy, awake human volunteers. Subjects were ventilated, via a mouthpiece, to achieve a stable end-tidal CO2 (PETCO2). After a 20-min baseline period the minute volume on the ventilator was passively increased by approximately 20% to reduce PETCO2 by 0.75-1 kPa. After a 10-min stabilization period the new PETCO2 level was maintained at a constant level for 20 min, and MCA FV recovery was measured during this 20-min period. Subjects undertook the protocol breathing air and breathing 100% oxygen. RESULTS: The PETCO2 level was (mean +/- SD) 4.9 +/- 0.4 kPa (normoxia baseline), 4.0 +/- 0.3 kPa (normoxia hyperventilation), 4.6 +/- 0.4 kPa (hyperoxia baseline) and 3.9 +/- 0.4 kPa (hyperoxia hyperventilation). CO2 reactivity was significantly lower with normoxia than hyperoxia (16.5 +/- 3.8 vs. 21.2 +/- 4.6 % kPa-1; P< 0.05). Middle cerebral artery FV recovery was significantly more rapid with normoxia than hyperoxia (0.23 +/- 0.17 vs. 0.08 +/- 0.1 % baseline min-1; P< 0.01). CONCLUSIONS: Our results suggest that cerebral hemodynamic responses to moderate hyperventilation are different in normoxic and hyperoxic conditions. Clinical assessment of CO2 reactivity and CBF recovery during hyperventilation should take the degree of arterial oxygenation into account.

Adult↗
PubMed2003

Assessment of the Ventrix parenchymal intracranial pressure monitoring probe (NL950-P) and Monitor (NL950-100) in a 3 Tesla magnetic resonance scanner.

Magnetic resonance (MR) imaging and spectroscopy provide important information in patients with acute head injury. However, optimal patient management requires intracranial pressure (ICP) monitoring. There are few reports on the use of ICP sensors in an MR environment. We tested the Ventrix parenchymal intracranial pressure monitoring probe and monitor (Integra Neurosciences, USA), modified by the use of a fibre-optic extension cable, within a 3 Tesla MR system. The device performed well in the MR environment, but one element within the fibre-optic extension was significantly ferromagnetic. The ICP probe produced a small susceptibility artefact on spin echo images, and a larger artefact on gradient echo images. The MR safety of the integrated system is probably acceptable, but could be easily improved with minor modifications. Although the system is MR compatible and produces generally acceptable imaging even at 3 Tesla, there is significant degradation of image quality during gradient echo sequences.

Artifacts↗
PubMed2003

Validation of a tonometric noninvasive arterial blood pressure monitor in the intensive care setting.

Intra-arterial measurement is considered the gold standard for continuous, beat-to-beat arterial blood pressure monitoring. However, arterial cannulation can be difficult and may cause complications such as thrombosis and ischaemia. Recently, a tonometric system, the Colin CBM-7000 has been developed for noninvasive beat-to-beat measurement of arterial blood pressure from the radial artery. We assessed the level of agreement between the CBM-7000 and invasive radial artery measurements in 15 patients on a neuro-intensive care unit. Agreement of systolic, diastolic and mean arterial pressure values was limited, with approximately 34% of mean arterial pressures differing by over 10 mmHg. In many cases, this was due to a downward drift of the noninvasive measurements over time. Furthermore, there was a tendency to underestimate low pressures and overestimate high pressures. In our opinion, the Colin CBM-7000 cannot be recommended for continuous blood pressure monitoring in the intensive care setting.

Adult↗
PubMed2003

A web-based system for teaching, assessment and examination of the undergraduate peri-operative medicine curriculum.

Today's students are generally computer literate and have high expectations of university information technology resources. Most United Kingdom medical schools now provide networked computers for learning, research, communication and accessing the worldwide web. We have exploited these advances to augment and improve the teaching of peri-operative medicine and anaesthesia to medical students in our university, who are taught in several hospitals over a wide geographical area. Course material such as departmental induction information, lecture notes and assessment sheets can be accessed online, contributing to the smooth running of the course. Streamed videos and simulations allow students to familiarise themselves with common practical procedures in advance. Development of a web-based end of course assessment has resulted in substantially less administration and bureaucracy for course organisers and proved to be a valuable research tool. Students' and teachers' opinions of the new course structure have been overwhelmingly positive.

Anesthesiology↗
PubMed2003

Cerebral oxygen vasoreactivity and cerebral tissue oxygen reactivity.

There has long been an appreciation that cerebral blood flow is modulated to ensure adequate cerebral oxygen delivery in the face of systemic hypoxaemia. There is increasing appreciation of the modulatory role of hyperoxia in the cerebral circulation and a consideration of the effects of such modulation on the maintenance of cerebral tissue oxygen concentration. These newer findings are particularly important in view of the fact that cerebrovascular and tissue oxygen responses to hyperoxia may change in disease. Such alterations provide important insights into pathophysiological mechanisms and may provide novel targets for therapy. However, before the modulatory effects of hyperoxia can be used for diagnosis, to predict prognosis or to direct therapy, a more detailed analysis and understanding of the physiological concepts behind this modulation are required, as are the limitations of the measurement tools used to define the modulation. This overview summarizes the available information in this area and suggests some avenues for further research.

Animals↗
PubMed2003

Effects of propofol on cerebral oxygenation and metabolism after head injury.

BACKGROUND: Flow-metabolism coupling is thought to be deranged after traumatic brain injury, while the effects of propofol on flow-metabolism coupling are controversial. We have used a step increase in target plasma propofol concentration in head injured patients to explore flow-metabolism coupling in these patients. METHODS: Ten patients with a moderate to severe head injury received a step increase in propofol target controlled infusion of 2 microg x ml(-1). Cerebral tissue gas measurements were recorded using a multimodal sensor, and regional chemistry was assessed using microdialysis. Arterial-jugular venous oxygen differences (AVDO(2)) were measured and all patients had cortical function monitoring (EEG). RESULTS: The step increase in propofol led to a large increase in EEG burst-suppression ratio (0% (range 0-1.1) to 46.1% (range 0-61.7), P<0.05); however, this did not significantly change tissue gas levels, tissue chemistry, or AVDO(2). CONCLUSIONS: Flow-metabolism coupling remains intact during a step increase in propofol after traumatic brain injury. The EEG burst-suppression induced by propofol after traumatic brain injury does not appear to be a useful therapeutic tool in reducing the level of regional ischaemic burden.

Adult↗
PubMed2003

Human cellular inflammation in the pathology of acute cerebral ischaemia.

Leucocytes form important effector pathways for inflammation. This article reviews the clinical evidence for the presence of a cellular inflammatory response in cerebral ischaemia, and attempts to define its temporal profile and spatial distribution. The processes involved in recruitment and activation of leucocytes in this context are addressed, and the successes and failures of interventions aimed at these processes discussed.

Acute Disease↗