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Biomedical subjects

J D Pickard

Publications and source records attributed to J D Pickard.

At least 127 records · Page 7Linked to original sources
PubMed2000

A new cranial access device for cerebral monitoring.

We report the design and clinical application of a new cranial access device (triple bolt) designed to transmit intracranial pressure monitors, multiparameter sensors, microdialysis catheters and laser doppler probes into the cerebral parenchyma. The objective was to achieve insertion on the Neuro-Critical Care Unit, imaging compatibility, angled trajectories and versatility of monitor application. The bolt has been successfully applied to 100 patients with severe head injury and subarachnoid haemorrhage.

Equipment Design↗
PubMed2000

Prediction of cerebral ischaemia during carotid endarterectomy with preoperative CO2-reactivity studies and angiography.

The objective of this study was to assess the value of combining the preoperative CO2 cerebrovascular reactivity index (CO2RI) with carotid and cerebral angiography in predicting the risk of severe cerebral ischaemia (SCI) during carotid endarterectomy (CEA). Seventy-four consecutive patients scheduled for CEA underwent preoperative digital subtraction angiography and CO2-reactivity tests. During CEA, cerebral function monitor (CFM) was used to document cortical electrical activity, whilst transcranial Doppler measured the middle cerebral artery flow velocity (FV). A persistent fall in CFM voltage and/or a fall in FV > or = 60% on internal carotid artery (ICA) clamping were used as criteria for defining SCI. Complete data from 59 patients were obtained for final analysis. Twelve cases showed a fall in FV > or = 60%; 11 of these also showed a sustained fall in CFM voltage. Using logistic regression, the risk of SCI was found to be negatively associated with (1) contralateral CO2RI, (2) the percentage stenosis of the contralateral ICA, and (3) the difference between ipsilateral and contralateral CO2RI. Using these factors, a logistic regression model for predicting the risk of SCI was established which provided a sensitivity of 75% and specificity of 100%. The risk of SCI during CEA was related to the contralateral ICA stenosis and the CO2RI of both cerebral hemispheres. This information may assist in presurgical planning and help to select asymptomatic carotid lesions for surgery.

Aged↗
PubMed2000

Maintaining and shifting attention within left or right hemifield.

Positron emission tomography (PET) was used to examine two questions: (i) which structures of the intact human brain change their activity with the direction of attention to left or right visual field; and (ii) how does activity in these structures, and in parietal cortex in particular, depend on the frequency of attentional shifts? Subjects were required to discriminate the orientation of peripheral gratings. The two main experimental variables were the attended hemifield (left or right) and the proportion of trials requiring a shift within that hemifield (20% or 80%). A detection control condition was also included. Behaviourally, subjects were less accurate and significantly slower when a trial required a shift than when it did not. Ventral and lateral occipital areas showed significantly higher blood flow levels contralateral to the direction of attention. Replicating previous work, there was also a significant main effect of the direction of attention in left lateral prefrontal cortex: blood flow levels were higher during leftward attention in comparison both to baseline and to rightward attention. This left frontal effect reached significance in single subjects in whom several activation sites could be distinguished within left middle and inferior frontal gyrus. Right and left parietal cortex were activated during both left- and right-field attention conditions, with a tendency for higher activity levels when attention was directed contralaterally. Contrary to the experimental hypothesis, however, parietal regions were not activated differentially by high versus low numbers of attentional shifts. The current experiment confirms that left frontal convexity is sensitive to manipulations of the direction of visuospatial attention. The results do not indicate a specific role of parietal cortex in attentional shifting.

Adult↗
PubMed2000

Potential role of NovoSeven in the prevention of rebleeding following aneurysmal subarachnoid haemorrhage.

Rebleeding following aneurysmal subarachnoid haemorrhage is a major factor contributing to unfavourable outcome. Antifibrinolytic agents reduce the rate of rebleeding but increase the risk of cerebral ischaemia and infarction and hence provide no overall benefit. To address the theoretical concern that recombinant activated factor VII (NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark) might increase the risk of cerebral ischaemia while stabilizing the clot at the site of aneurysmal rupture, an open-label, dose-escalation safety study has been developed in collaboration with the UK Spontaneous Intracranial Haemorrhage Group. The trial design includes the recruitment of 15 patients (aged 18 years or over) in good grade with subarachnoid haemorrhage verified by computerized tomography scan or lumbar puncture. Safety evaluation includes clinical observation, monitoring of laboratory variables, positron emission tomography (PET) scanning (rCBF, rOEF, rCMRO2) and transcranial Doppler ultrasound. To date, ten patients have been recruited [NovoSeven 80 microg/kg single bolus (n = 2), NovoSeven 80 microg/kg single bolus followed by continuous infusion at 3.5 microg/kg per h (n = 2) or 7 microg/kg per h (n = 1), or control (n = 5)]. Clinical observation, transcranial Doppler ultrasound and PET studies revealed no evidence of cerebral ischaemia in the first nine patients treated with NovoSeven. The last patient developed middle cerebral artery branch thrombosis contralateral to the aneurysm. The study is currently suspended pending further investigation.

Adult↗
PubMed2000

Syntheses of the first endothelin-A- and -B-selective radioligands for positron emission tomography.

We have synthesized two potential positron emission tomography (PET) radioligands for the endothelin (ET) receptor. [11C]-PD156707 was produced by O-methylation of PD169390 using [11C]iodomethane. Radiochemical conversions of the order of 74 +/- 3.2% (n = 8) were obtained. The radiochemical purity of the isolated [11C]-PD156707 was 99% and the specific activity was 538 mCi/micromol. [18F]-BQ3020 was produced from [18F]fluoride in a total radiochemical yield of 2.7 +/- 0.4% (n = 10) in 238 +/- 5 min. The radiochemical purity was 95% and specific activities of the order of 670-930 mCi/micromol were obtained.

Amino Acid Sequence↗
PubMed2000

Predicting delayed ischemic deficits after aneurysmal subarachnoid hemorrhage using a transient hyperemic response test of cerebral autoregulation.

OBJECTIVE: To assess whether the development of delayed ischemic deficits (DIDs) after aneurysmal subarachnoid hemorrhage can be predicted using transcranial Doppler ultrasonography and the transient hyperemic response test (THRT). METHODS: An increase in the middle cerebral artery peak flow velocity (FV) of more than 9% of baseline values after 5 to 9 seconds of carotid artery compression was defined as a normal THRT result, indicating good autoregulatory reserve. The transcranial Doppler criteria for vasospasm were a FV of more than 120 cm/s and a Lindegaard ratio of more than 3. Twenty patients with no immediate postoperative neurological deficits were studied. The FVs at all of the major cerebral arteries were measured daily after surgery, and the THRT results were assessed bilaterally. RESULTS: Five of six patients with abnormal THRT results in the first examination after surgery (primary THRT impairment) developed DIDs; none of the remaining patients developed DIDs (Fisher exact test, P = 0.0004). All five patients with DIDs initially exhibited low FVs but all subsequently developed increases in FVs to values of more than 150 cm/s and four exhibited FVs of more than 200 cm/s. The time of onset of DIDs corresponded to the time of onset of moderate vasospasm (FV > 150 cm/s). None of the patients with initially normal THRT results developed DIDs, although four patients did exhibit late (secondary) THRT impairment, which was associated with FVs of more than 120 cm/s. CONCLUSION: When the effects of primarily impaired (after surgery) autoregulation are magnified by vasospasm, the risk of DIDs seems to be very high. Vasospasm alone does not seem to cause DIDs. The development of DIDs could therefore be predicted using the THRT for patients after aneurysm clipping.

Adult↗
PubMed2000

Clinical cerebral microdialysis: a methodological study.

OBJECT: Clinical microdialysis enables monitoring of the cerebral extracellular chemistry of neurosurgical patients. Introduction of the technique into different hospitals' neurosurgical units has resulted in variations in the method of application. There are several variables to be considered, including length of the catheter membrane, type of perfusion fluid, flow rate of perfusion fluid, and on-line compared with delayed analysis of samples. The objects of this study were as follows: 1) to determine the effects of varying catheter characteristics on substance concentration; 2) to determine the relative recovery and true extracellular concentration by varying the flow rate and extrapolating to zero flow; and 3) to compare substance concentration obtained using a bedside enzyme analyzer with that of off-line high-performance liquid chromatography (HPLC). METHODS: A specially designed bolt was used to conduct two adjacent microdialysis catheters into the frontal cortex of patients with head injury or poor-grade subarachnoid hemorrhage who were receiving ventilation. One reference catheter (10-mm membrane, perfused with Ringer's solution at 0.3 microl/minute) was constant for all studies. The other catheter was varied in terms of membrane length (10 mm or 30 mm), perfusion fluid (Ringer's solution or normal saline), and flow rate (0.1-1.5 microl/minute). The effect of freezing the samples on substance concentration was established by on-line analysis and then repeated analysis after storage at -70 degrees C for 3 months. Samples assayed with the bedside enzyme analyzer were reassessed using HPLC for the determination of glutamate concentrations. CONCLUSIONS: Two adjacent microdialysis catheters that were identical in membrane length, perfusion fluid, and flow rate showed equivalent results. Variations in perfusion fluid and freezing and thawing of samples did not result in differences in substance concentration. Catheter length had a significant impact on substance recovery. Variations in flow rate enabled the relative recovery to be calculated using a modification of the extrapolation-to-zero-flow method. The recovery was approximately 70% at 0.3 microl/minute and 30% at 1 microl/minute (10-mm membrane) for all analytes. Glutamate results obtained with the enzyme analyzer showed good correlation with those from HPLC.

Adult↗
PubMed2000

Efficacy and safety of the endothelin, receptor antagonist TAK-044 in treating subarachnoid hemorrhage: a report by the Steering Committee on behalf of the UK/Netherlands/Eire TAK-044 Subarachnoid Haemorrhage Study Group.

OBJECT: Delayed cerebral ischemia remains an important cause of death and disability in patients who have suffered subarachnoid hemorrhage (SAH). Endothelin (ET) has a potent contractile effect on cerebral arteries and arterioles and has been implicated in vasospasm. The authors administered ET(A/B) receptor antagonist (TAK-044) to patients suffering from aneurysmal SAH. They then assessed whether this agent reduced the occurrence of delayed cerebral ischemic events and examined its safety profile in this group of patients. METHODS: Four hundred twenty patients who had suffered an SAH were recruited into a multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II trial. The primary end point was whether a delayed ischemic event occurred within 3 months after the first dose of the study drug and the secondary end points included determining whether a delayed ischemic event occurred by 10 days after the first dose of the study drug, whether a new cerebral infarct was demonstrated on a computerized tomography scan or at postmortem examination by 3 months after administration of the initial dose, the patient's Glasgow Outcome Scale scores at 3 months after the initial dose, and adverse events. There was a lower incidence of delayed ischemic events at 3 months in the TAK-044-treated group: 29.5% compared with 36.6% in a group of patients receiving placebo. The estimated relative risk was 0.8 with a 95% confidence interval of 0.61 to 1.06. There were no significant differences in the secondary end points, including clinical outcomes in the placebo-treated and TAK-044-treated groups. CONCLUSIONS: The TAK-044 was well tolerated by patients who had suffered an SAH, even though hypotension and headache--side effects compatible with the drug's vasodilatory properties--occurred. It would be valuable to proceed to a fully powered phase III trial of an ET receptor antagonist in treating aneurysmal SAH.

Adult↗
PubMed2000

Biochemical changes related to hypoxia during cerebral aneurysm surgery: combined microdialysis and tissue oxygen monitoring: case report.

OBJECTIVE AND IMPORTANCE: The objective of this study was to monitor brain metabolism on-line during aneurysm surgery, by combining the use of a multiparameter (brain tissue oxygen, brain carbon dioxide, pH, and temperature) sensor with microdialysis (extracellular glucose, lactate, pyruvate, and glutamate). The case illustrates the potential value of these techniques by demonstrating the effects of adverse physiological events on brain metabolism and the ability to assist in both intraoperative and postoperative decision-making. CLINICAL PRESENTATION: A 41-year-old woman presented with a World Federation of Neurological Surgeons Grade I subarachnoid hemorrhage. Angiography revealed a basilar artery aneurysm that was not amenable to coiling, so the aneurysm was clipped. Before the craniotomy was performed, a multiparameter sensor and a microdialysis catheter were inserted to monitor brain metabolism. INTERVENTION: During the operation, the brain oxygen level decreased, in relation to biochemical changes, including the reduction of extracellular glucose and pyruvate and the elevation of lactate and glutamate. These changes were reversible. However, when the craniotomy was closed, a second decrease in brain oxygen occurred in association with brain swelling, which immediately prompted a postoperative computed tomographic scan. The scan demonstrated acute hydrocephalus, requiring external ventricular drainage. The patient made a full recovery. CONCLUSION: The monitoring techniques influenced clinical decision-making in the treatment of this patient. On-line measurement of brain tissue gases and extracellular chemistry has the potential to assist in the perioperative and postoperative management of patients undergoing complex cerebrovascular surgery and to establish the effects of intervention on brain homeostasis.

Adult↗
PubMed1999

Choosing between small, likely rewards and large, unlikely rewards activates inferior and orbital prefrontal cortex.

Patients sustaining lesions of the orbital prefrontal cortex (PFC) exhibit marked impairments in the performance of laboratory-based gambling, or risk-taking, tasks, suggesting that this part of the human PFC contributes to decision-making cognition. However, to date, little is known about the particular regions of the orbital cortex that participate in this function. In the present study, eight healthy volunteers were scanned, using H(2)(15)0 PET technology, while performing a novel computerized risk-taking task. The task involved predicting which of two mutually exclusive outcomes would occur, but critically, the larger reward (and penalty) was associated with choice of the least likely outcome, whereas the smallest reward (and penalty) was associated with choice of the most likely outcome. Resolving these "conflicting" decisions was associated with three distinct foci of regional cerebral blood flow increase within the right inferior and orbital PFC: laterally, in the anterior part of the middle frontal gyrus [Brodmann area 10 (BA 10)], medially, in the orbital gyrus (BA 11), and posteriorly, in the anterior portion of the inferior frontal gyrus (BA 47). By contrast, increases in the degree of conflict inherent in these decisions was associated with only limited changes in activity within orbital PFC and the anterior cingulate cortex. These results suggest that decision making recruits neural activity from multiple regions of the inferior PFC that receive information from a diverse set of cortical and limbic inputs, and that the contribution of the orbitofrontal regions may involve processing changes in reward-related information.

Adult↗
PubMed1999

Delayed induction of JunB precedes CA1 neuronal death after global ischemia in the gerbil.

The immediate early genes (IEGs), c-jun, junB and c-fos are expressed after global ischemia in the gerbil. The role of these genes remains unclear. Whilst moderate ischemia (7 min) causes delayed CA1 neuronal death, pre-conditioning with mild ischemia (2 min) neuroprotects the CA1 subfield. This differential response allows the specific expression patterns of IEGs to be associated with either delayed neuronal death, or cell survival, depending upon the insult severity. Using a graded insult strategy we have shown that (1) early IEG expression is prominent in the neuronal layers of the CA3, hilar and dentate regions, and (2) a delayed, secondary wave of JunB expression is localized to the selectively vulnerable CA1 neuronal layer after moderate ischemia. This expression precedes the histological and histochemical features of neuronal death. Delayed JunB expression was not observed in animals subject to 2 min ischemia. The glial fibrillary acidic protein (GFAP) promotor possesses an AP-1 binding site, the target for IEG dimers. To examine the possible link between IEG expression and astrocyte activation the transcriptional activation of GFAP was assessed. GFAP mRNA was evident within 8 h of ischemia after both insults. The extent of the astrocytic reaction was dependent upon the severity of the ischemia. The temporospatial distribution of IEG and GFAP expression differed, indicating that glial activation is unlikely to be regulated by the hippocampal expression of IEGs. We conclude that early IEG expression is involved in signalling mechanisms that invoke neuroprotective effects in the dentate and CA3 regions, and that delayed JunB expression in the CA1 subfield is associated with neuronal death, and may be involved in the commitment or execution phases of cell death. Early astrocytic responses may play a role in the mechanism of ischaemic tolerance.

Animals↗
PubMed1999

Monitoring by subcutaneous microdialysis in neurosurgical intensive care.

Microdialysis is an in vivo sampling technique which provides a powerful approach to monitoring metabolic events. We have performed a study to determine the feasibility and effectiveness of subcutaneous microdialysis in monitoring patients on the Neurosurgical Intensive Care Unit (NICU). A microdialysis probe was placed in the subcutaneous fat of the anterior abdominal wall and perfused with Ringer's solution. Collecting vials were changed every 30 minutes and monitoring continued for 2-6 days. Biochemical analysis of glucose, lactate, and glutamate was correlated with clinical events. The normal ranges of glucose, lactate and glutamate were 3-6 mM. 1-2.5 mM and 5-20 microM, respectively. Periods of low tissue glucose were detected by microdialysis which were not detected by routine plasma sampling. In one patient, following an apparently brief period of hypoxia, there was a prolonged disturbance of tissue chemistry. Another patient with obesity had significantly higher concentrations of dialysate glucose, lactate and glutamate. Monitoring by subcutaneous microdialysis on intensive care units is feasible, reveals unexpected changes in tissue metabolism and might be an important adjunct for the interpretation of intracerebral data.

Adolescent↗
PubMed1999

Assessment of critical closing pressure in the cerebral circulation as a measure of cerebrovascular tone.

Critical closing pressure (CCP) calculated from the blood flow velocity (FV) and arterial blood pressure (ABP) waveforms has been previously reported to be useful in the assessment of the dynamics of cerebral circulation. We investigated the relationship between CCP and intracranial pressure (ICP) and cerebrovascular tone in a model of intracranial hypertension in 22 anaesthetised New Zealand White rabbits during manipulations of arterial CO2, ABP and vasodilatation caused by hypoxia. Recordings were made of FV in the basilar artery, ABP and ICP during subarachnoid infusion of saline. During infusion ICP and CCP were significantly correlated (R=0.68; p<0.001), but the magnitude of increase in ICP and CCP during infusion were not correlated to each other. Linear regression between the difference: CCP-ICP (representing a factor due to vasogenic tone) and cerebral perfusion pressure (CPP=ABP-ICP) was highly significant (R=-0.87; p<0.01). Generally, CCP decreased significantly (p<0.05) with hypercarbia, arterial hypotension and after and post-hypoxia and the difference: CCP-ICP decreased consistently after each vasodilatatory manoeuvre studied. Our data confirmed the linear relationship between CCP and ICP, and between the difference: CCP-ICP and cerebrovascular tone. However, because the magnitude of increase in ICP was not correlated to magnitude of change in CCP, CCP cannot be use for detection of increasing ICP quantitatively.

Animals↗
PubMed1999

Vasoconstriction in human isolated middle meningeal arteries: determining the contribution of 5-HT1B- and 5-HT1F-receptor activation.

AIMS: Sumatriptan is a 5-HT1B/1D-receptor agonist which also has affinity for 5-HT1F-receptors. The vasoconstrictor effects of sumatriptan are thought to be 5-HT1B-receptor mediated and these receptors have been shown to be expressed in human cranial blood vessels. However, in the same tissue mRNA coding for 5-HT1F-receptors has also been identified and this study addresses the possibility of whether 5-HT1F-receptor activation contributes to vasoconstriction. METHODS: The ability of two selective 5-HT1B/1D-receptor antagonists (GR125,743 and GR127,935) with no affinity for 5-HT1F-receptors, to inhibit sumatriptan evoked contractions in human isolated middle meningeal artery was investigated. Using a series of 5-HT1B/1D-receptor agonists (sumatriptan, zolmitriptan, CP122,288, L-741,519 and L-741,604), some with high affinity for 5-HTIF-receptors and the non-selective 5-HT-receptor agonists 5-HT and 5-CT, we compared the vasoconstrictor potency of these drugs in human isolated middle meningeal artery with their affinities at cloned human 5-HT1B-, 5-HT1D-and 5-HT1F-receptors expressed in CHO cell lines. RESULTS: GR125,743 antagonized sumatriptan evoked contractions in a competitive manner (apparent pA2 9.1) and GR127,935 antagonized sumatriptan-induced responses in a non-competitive manner (reducing the maximum contraction to 27%). There was a significant correlation between vasoconstrictor potency and 5-HT1B-receptor affinity (r=0.93, P=0.002) but not with 5-HT1D- or 5-HT1F-receptor affinity (r=0.74, P=0.06; r= 0.31, P= 0.49, respectively). CONCLUSIONS: These experiments show that in human middle meningeal artery vasoconstriction to sumatriptan-like agents is 5-HT1B-receptor mediated with little if any contribution from 5-HT1F-receptor activation.

Animals↗