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Biomedical subjects

J D Pickard

Publications and source records attributed to J D Pickard.

At least 91 records · Page 5Linked to original sources
PubMed2002

Clinical cerebral microdialysis--determining the true extracellular concentration.

Current monitoring of the cerebral extracellular chemistry of neurosurgical patients using microdialysis does not provide the true extracellular concentration because full equilibration across the membrane is not achieved. By varying the flow rate and extrapolating to zero flow, the relative recovery i.e. the concentration of the substance in the microdialysate as a proportion of the true concentration in the extracellular space may be calculated. The disadvantage of this method is that it depends on the underlying baseline chemistry being constant during measurements for the calculations, which is not the case in the changing environment of a neuro-intensive unit. We have therefore designed a modification of the extrapolation to zero flow method using an adjacent constant flow rate catheter to monitor the baseline. The results demonstrate that the relative recovery varies considerably with flow rate, and for the CMA70 10 mm membrane catheter, is approximately 70% at a rate of 0.3 microliter/min and 30% at a rate of 1.0 microliter/min for glucose, lactate, pyruvate and glutamate.

Biomarkers↗
PubMed2002

Extracellular lactate/pyruvate and glutamate changes in patients during per-operative episodes of cerebral ischaemia.

OBJECTIVE: Temporary Internal Carotid Artery (ICA) clipping necessary during aneurysm surgery was used as a model to investigate metabolic changes in the human brain during defined episodes of ischaemia. DESIGN: An observational study using intracerebral monitors: PBO2 (Neurotrend) and microdialysis (CMA, Sweden). SUBJECTS: 16 patients monitored during complex aneurysm surgery. OUTCOME MEASURES: Changes in extracellular concentrations of glucose, lactate, and glutamate and lactate/pyruvate ratio (L/P). RESULTS: Mean age was 55. 10 patients presented with subarachnoid haemorrhage and 6 with mass effect (4 giant). Temporary ICA occlusion was required for dissection (n = 9), intraoperative rupture (n = 5) or aneurysmal thrombectomy (n = 2). The mean total duration was 15 minutes (range 4-52 minutes). No infarcts developed in the monitored regions. Microdialysis was unsuccessful in 3 patients and Neurotrend in 1. Patients were grouped according to the degree and duration of fall in PBO2: minimal brief falls were not associated with microdialysis changes (n = 5). More pronounced falls were associated with increases in L/P (n = 4). Only prolonged occlusions averaging 42 minutes (n = 3) with PBO2 sustained below 1 kPa were associated with rises in glutamate. CONCLUSIONS: Brief temporary ICA occlusion caused an initial increased L/P. Glutamate increases were only seen after occlusion that was prolonged with PBO2 below 1.0 kPa.

Adult↗
PubMed2002

Laboratory testing of hydrocephalus shunts -- conclusion of the U.K. Shunt evaluation programme.

16 models of valves, currently in use in the U.K., have been tested long-term in the U.K. Shunt Evaluation Laboratory according to the protocol based on the new ISO 7197 standard. Valves tested were: Medtronic PS Medical: Delta Valve, Flow Control and Lumbo-Peritoneal Shunt, Heyer-Schulte Nero-Care: In-line, Low Profile and Pudenz Flushing Valve, Codman: Codman-Hakim Programmable, Hakim Precision, Accu-Flo, Holter, Uni-Shunt, and siphon-preventing device -- SiphonGuard, NMT: Orbis-Sigma Valve, Omni-Shunt and Hakim Valve, Sophysa: Sophy Programmable Valve, Radionics: Contour-Flex Valve. The majority of the valves had a non-physiologically low hydrodynamic resistance (with the exception of Orbis-Sigma, PS Lumbo-Peritoneal and Heyer-Schulte In-Line). This may result in overdrainage both related to posture and during nocturnal cerebral vasogenic waves. A long distal catheter increases the resistance of these valves by 100-200%. Drainage through valves without siphon-preventing mechanism is very sensitive to body posture. This may produce grossly negative intracranial pressure after implantation. A few shunts (Delta, Low Profile and Pudenz-Flushing with Anti-Siphon Devices) offer a reasonable resistance to negative outlet pressure, and hence potentially might prevent complications related to overdrainage. On the other hand, valves with siphon-preventing devices may be blocked by raised subcutaneous pressure (exception: SiphonGuard, but this device may block the drainage because of its faulty design). In most of the silicone-diaphragm valves, closing pressure varied and reached values lower than that specified by the manufacturer (exception: Heyer-Schulte Pudenz Flushing Valve). All programmable valves are susceptible to overdrainage in the upright body position. Programmed settings may be changed by external magnetic fields. Most shunts are very sensitive to the presence of small particles in the drained fluid. The behavior of a valve revealed during such testing is of immediate relevance to the surgeon and may not be adequately described in the manufacturer's product information. These results are also relevant to the assessment of shunt function in-vivo using an infusion test.

Cerebrospinal Fluid Pressure↗
PubMed2002

5-HT1B-receptors and vascular reactivity in human isolated blood vessels: assessment of the potential craniovascular selectivity of sumatriptan.

AIMS: 5-HT1B-receptor mediated vasoconstriction of cranial arteries is a potential mechanism by which 5-HT1B/1D-receptor agonists such as sumatriptan produce their antimigraine effects. 5-HT1B-receptors exist in other blood vessels which may give rise to unwanted vascular effects. Therefore we examined the distribution of 5-HT1B-receptor immunoreactivity (i.r.) in human blood vessels (including target and nontarget vessels) and confirmed the functionality of this receptor protein, by comparing the vasoconstrictor effects of sumatriptan and 5-HT (the endogenous ligand) in isolated vessels. METHODS: Blood vessels (middle meningeal, pial, temporal and uterine arteries and saphenous veins) were obtained from surgical patients (with consent). Sections of the vessels were prepared for routine immunohistochemical studies using specific 5-HT1B- and 5-HT1D-receptor antibodies. For functional studies, ring segments of the vessels were mounted in organ baths for isometric tension recording. RESULTS: 5-HT1B-receptor i.r. was detected on the smooth muscle layer in middle meningeal, pial and uterine arteries and in saphenous vein and sumatriptan produced contractions in these vessels with potency values (mean pEC50) of 7.00, 7.08, 6.44 and 6.61, respectively, the magnitude of contraction was greatest in the cranial arteries with Emax values of 100.7, 60.3, 23.0 and 35.9%, respectively (expressed as a percentage of the reference agonist 45 mm KCl). 5-HT1B-receptor i.r. was not detected in temporal artery and sumatriptan had no effect in this artery. 5-HT1D-receptor i.r. was not detected in any of the vessels studied. CONCLUSIONS: Sumatriptan can evoke vasoconstriction in antimigraine target vessels and also in nontarget vessels through an action at 5-HT1B-rcceptors. Sumatriptan acts preferentially to cause contraction in human cranial arteries compared with the other blood vessels we examined and this effect is likely to be shared by other drugs of this class.

Cerebral Veins↗
PubMed2002

Investigation of the effect of chlormethiazole on cerebral chemistry in neurosurgical patients: a combined study of microdialysis and a neuroprotective agent.

AIMS: Promising pre-clinical results from laboratory studies of neuro-protective drugs for the treatment of patients with stroke and head injury have not been translated into benefit during clinical trials. The objective of the study was to assess the feasibility of administrating a potential neuro-protective drug (chlormethiazole) in conjunction with multimodality monitoring (including microdialysis) to patients with severe head injury in order to determine the effect of the agent on surrogate endpoints and penetration into the brain. METHODS: Multimodality monitoring including cerebral and peripheral microdialysis was applied to five head-injured patients on the neuro-intensive care unit. Chlormethiazole (0.8%) was administered as a rapid (10 ml min(-1)) intravenous loading infusion for 5 min followed by a slow (1 ml min(-1)) continuous infusion for 60 min. The following parameters were monitored: heart rate, mean arterial blood pressure, intracranial pressure, cerebral perfusion pressure, peripheral oxygen saturation, continuous arterial oxygen partial pressure, arterial carbon dioxide partial pressure, arterial pH, arterial temperature, cerebral tissue oxygen pressure, cerebral tissue carbon dioxide pressure, cerebral pH, cerebral temperature, electroencephalograph (EEG), bi-spectral index, plasma glucose, plasma chlormethiazole, and cerebral and peripheral microdialysis assay for chlormethiazole, glucose, lactate, pyruvate and amino acids. RESULTS: Despite achieving adequate plasma concentrations, chlormethiazole was not detected in the peripheral or cerebral microdialysis samples. The drug was well tolerated and did not induce hypotension, hyperglycaemia or withdrawal seizures. The drug did not change the values of the physiological or chemical parameters including levels of GABA, lactate/pyruvate ratio and glutamate. The drug did, however, induce EEG changes, including burst suppression in two patients. CONCLUSIONS: Chlormethiazole can be safely given to ventilated patients with severe head injury. There was no evidence of hypotension or withdrawal seizures. Combining a pilot clinical study of a neuro-protective agent with multimodality monitoring is feasible and, despite the lack of effect on physiological and chemical parameters in this study, may be a useful adjunct to the development of neuro-protective drugs in the future. Further investigation of the capability of microdialysis in this setting is required. By investigating the effect of a drug on surrogate end-points, it may be possible to identify promising agents from small pilot clinical studies before embarking on large phase III clinical trials.

Adult↗
PubMed2002

A laboratory model of testing shunt performance after implantation.

Constant rate infusion tests are used clinically to test shunt function in vivo in hydrocephalic patients. The criteria for appropriate shunt function have never been validated in the laboratory. Nine of the most commonly used types of hydrocephalus valves construction were selected and tested in a model of the CSF circulation incorporating increased resistance to CSF outflow [24 mmHg/(ml/min)] and decreased hydrodynamic compliance (<2 ml/mmHg), that are typical conditions in hydrocephalus. The aim was to document the pressure response to constant rate infusion of a model of CSF circulation with different valves and to define which measures are useful in shunt testing in vivo. The pressure-course of simulated CSF pressure was established and proved to be equivalent to clinical results. The baseline CSF pressure failed to correlate with shunt operating pressure for medium pressure valves (R = 0.14, p > 0.05). End-equilibrium pressure recorded during infusion correlated strongly with the opening pressure (R = 0.94, p = 0.0001) and the shunt's resistance (R = 0.86, p = 0.0026). The infusion test is able to assess shunt function. End-equilibrium pressure recorded during the test has been confirmed to correlate with the shunt's performance.

Cerebrospinal Fluid Pressure↗
PubMed2002

How can we measure substrate, metabolite and neurotransmitter concentrations in the human brain?

Cerebral injury and disease is associated with fundamental derangements in metabolism, with changes in the concentration of important substrates (e.g. glucose), metabolites (e.g. lactate) and neurotransmitters (e.g. glutamate and y-aminobutyric acid) in addition to changes in oxygen utilization. The ability to measure these substances in the human brain is increasing our understanding of the pathophysiology of trauma, stroke, epilepsy and tumours. There are several techniques in clinical practice already in use and new methods are under evaluation. Such techniques include the use of cerebral probes (e.g. microdialysis. voltammetry and spectrophotometry) and functional imaging (e.g. positron emission tomography and magnetic resonance spectroscopy). This review describes these techniques in terms of their principles and clinical applications.

Brain↗
PubMed2002

Increases in GABA concentrations during cerebral ischaemia: a microdialysis study of extracellular amino acids.

OBJECTIVES: Increases in the extracellular concentration of the excitatory amino acids glutamate and aspartate during cerebral ischaemia in patients are well recognised. Less emphasis has been placed on the concentrations of the inhibitory amino acid neurotransmitters, notably gamma-amino-butyric acid (GABA), despite evidence from animal studies that GABA may act as a neuroprotectant in models of ischaemia. The objective of this study was to investigate the concentrations of various excitatory, inhibitory and non-transmitter amino acids under basal conditions and during periods of cerebral ischaemia in patients with head injury or a subarachnoid haemorrhage. METHODS: Cerebral microdialysis was established in 12 patients with head injury (n=7) or subarachnoid haemorrhage (n=5). Analysis was performed using high performance liquid chromatography for a total of 19 (excitatory, inhibitory and non-transmitter) amino acids. Patients were monitored in neurointensive care or during aneurysm clipping. RESULTS: During stable periods of monitoring the concentrations of amino acids were relatively constant enabling basal values to be established. In six patients, cerebral ischaemia was associated with increases (up to 1350 fold) in the concentration of GABA, in addition to the glutamate and aspartate. Parallel increases in the concentration of glutamate and GABA were found (r=0.71, p<0.005). CONCLUSIONS: The results suggest that, in the human brain, acute cerebral ischaemia is not accompanied by an imbalance between excitatory and inhibitory amino acids, but by an increase in all neurotransmitter amino acids. These findings concur with the animal models of ischaemia and raise the possibility of an endogenous GABA mediated neuroprotective mechanism in humans.

Adolescent↗
PubMed2001

Principles of quality management in medicine: the British concept.

The National Health Service in Great Britain is undergoing radical change particularly with regard to clinical governance, self-regulation, revalidation, career structures and training and patterns of healthcare delivery. All these changes are relevant to risk-control and quality management. This review surveys these generic changes and illustrates the implications for neurosurgery. Neurosurgery in the UK has the opportunity to enhance their patients care by expanding the number of consultants, developing further sub-specialisation and enhancing its training and review and dissemination programmes but only if extra resources are provided.

Diffusion of Innovation↗
PubMed2001

Normal pressure hydrocephalus and cerebral blood flow: a review.

Normal pressure hydrocephalus is a neurological disease which poses both diagnostic and therapeutic problems for the clinician. The measurement and characterisation of cerebral blood flow has been proposed as a tool for resolving such problems as well as elucidating its pathophysiology. We review the results of studies in which this tool has been applied to normal pressure hydrocephalus patients and consider the merits of the techniques that have been utilised. Finally, consideration is given to feasible future studies and the methods that could be employed in the study of cerebral blood flow and metabolism in patients with normal pressure hydrocephalus.

Brain↗
PubMed2001

Bifrontal decompressive craniectomy in the management of posttraumatic intracranial hypertension.

Bifrontal decompressive craniectomy has been used on an ad hoc basis for the treatment of post-traumatic intracranial hypertension for more than thirty years. In this observational study we report the clinical outcome and physiological effects of the procedure in a series of 26 patients with refractory intracranial hypertension treated on a protocol driven basis. Bifrontal decompressive craniectomy was associated with significant reductions in mean ICP from 37.5 to 18.1 mmHg (p = 0.003). In addition, craniectomy reduced the amplitude of ICP waves (p < 0.02) and increased compensatory reserve (p < 0.05). A favourable outcome was achieved in 69% of patients; 8% were severely disabled and 23% died. We conclude that this study provides pathophysiological evidence that bifrontal decompressive craniectomy significantly reduces posttraumatic intracranial hypertension and improves pressure dynamics. Our results support the continued use of bifrontal decompressive craniectomy in selected patients after head injury.

Adolescent↗
PubMed2001

A model of the cerebral and cerebrospinal fluid circulations to examine asymmetry in cerebrovascular reactivity.

The authors examined the steal phenomenon using a new mathematical model of cerebral blood flow and the cerebrospinal fluid circulation. In this model, the two hemispheres are connected through the circle of Willis by an anterior communicating artery (ACoA) of varying size. The right hemisphere has no cerebrovascular reactivity and the left is normally reactive. The authors studied the asymmetry of hemispheric blood flow in response to simulated changes in arterial blood pressure and carbon dioxide concentration. The hemispheric blood flow was dependent on the local regulatory capacity but not on the size of the ACoA. Flow through the ACoA and carotid artery was strongly dependent on the size of the communicating artery. A global interhemispheric "steal effect" was demonstrated to be unlikely to occur in subjects with nonstenosed carotid arteries. Vasoreactive effects on intracranial pressure had a major influence on the circulation in both hemispheres, provoking additional changes in blood flow on the nonregulating side. A method for the quantification of the crosscirculatory capacity has been proposed.

Blood Pressure↗
PubMed2001

Uncoupling of cerebral blood flow and metabolism after cerebral contusion in the rat.

Positron emission tomography scans of patients with head injuries often show discrete areas of increased 18F-fluorodeoxyglucose uptake ("hot spots") when performed hours to days after the initial ictus. Using quantitative autoradiographic methods, the authors have investigated whether cerebral blood flow and glucose metabolism are uncoupled 2 hours after controlled head injury in an animal model, and whether any "hot spots" are accompanied by changes in cerebral glucose concentration. Experiments were performed on 18 anesthetized, ventilated (1.5% halothane in 2:1 nitrous oxide:oxygen) Sprague-Dawley rats weighing 300 to 330 g. A burr hole was made over the left parietal cortex, and all animals received a piston impact on the intact dura (2 mm in diameter, 2.0 m/sec, 2 mm in depth). All animals remained anesthetized and ventilated for a further 2 hours, after which quantitative autoradiography was used to determine either (1) local cerebral blood flow (LCBF) using 14C-iodoantipyrine, (2) local cerebral glucose utilization (LCGU) using 14C-deoxyglucose, or (3) local cerebral glucose content (LCGC) using 14C-methylglucose. Local CBF, LCGU, and LCGC were measured in five regions adjacent to the contusion, and values then were normalized on the contralateral cortex. Normalized LCBF, LCGU, or LCGC varied in parallel in ipsilateral cortex (no change) and in the ischemic core of the contusion (reduced). However, there were marked changes in the patterns observed in the boundary zone (within 1 mm of the contusion). In all six rats used for LCGU measurement, there were discrete areas of high metabolism, whereas in all six rats used for LCBF measurement, flow was universally depressed in the boundary zone. Of the six rats used for LCGC determination, there was a discrete area of high signal in only one. The authors conclude that there are discrete areas of uncoupling of cerebral blood flow and metabolism after head injury within 2 hours of cerebral contusion in the rat that cannot be explained by changes in cerebral glucose content in the majority of animals.

Animals↗
PubMed2001

Laboratory evaluation of the phoenix CRx diamond valve.

OBJECTIVE: To assess the long-term hydrodynamic properties of a new cerebrospinal fluid flow-regulating hydrocephalus shunt called the CRx Diamond valve (Phoenix Biomedical Corp., Valley Forge, PA). METHODS: Three samples of a Diamond valve were tested in the United Kingdom Shunt Evaluation Laboratory during a 40-day period. Tests were performed for long-term pressure-flow performance, overdrainage, susceptibility to ambient temperature changes, external pressure, reflux, presence of small particles in the reagent, mechanical durability, and magnetic resonance imaging compatibility. RESULTS: Tests demonstrated that the Diamond valve stabilized flow within the range of 0.36 to 0.62 ml/min when pressure varied from 14 to 23 mm Hg. Hydrodynamic resistance demonstrated pressure-dependent variability from 20 to 78 mm Hg/(ml/min). The time drift of hydrodynamic parameters was significant (P < 0.001). The valve was insensitive to changes in temperature, external pressure, rapid fluctuations of differential pressure, small particles in fluid, and reflux. CONCLUSION: The Diamond valve demonstrated the intended variable resistance, which increased as the pressure increased. This property may help it limit overdrainage related to body posture as well as nocturnal vasogenic waves. Flow through the valve stabilizes within a wide range, which may contribute to the prevention of excessive pressure buildup after implantation. However, shunt placement should be avoided in patients who present with normal baseline intracranial pressure but an increased incidence of high vasogenic intracranial pressure waves.

Cerebrospinal Fluid Shunts↗
PubMed2001

Cerebral venous blood outflow: a theoretical model based on laboratory simulation.

OBJECTIVE: The cerebrovascular bed and cerebrospinal fluid circulation have been modeled extensively except for the cerebral venous outflow, which is the object of this study. METHODS: A hydraulic experiment was designed for perfusion of a collapsible tube in a pressurized chamber to simulate the venous outflow from the cranial cavity. CONCEPT: The laboratory measurements demonstrate that the majority of change in venous flow can be attributed to either inflow pressure when the outflow is open, or the upstream transmural pressure when outflow is collapsed. On this basis, we propose a mathematical model for pressure distribution along the venous outflow pathway depending on cerebral blood flow and intracranial pressure. The model explains the physiological strong coupling between intracranial pressure and venous pressure in the bridging veins, and we discuss the limits of applicability of the Starling resistor formula to the venous flow rates. The model provides a complementary explanation for ventricular collapse and origin of subdural hematomas resulting from overshunting in hydrocephalus. The noncontinuous pressure flow characteristic of the venous outflow is pinpointed as a possible source of the spontaneous generation of intracranial slow waves. CONCLUSION: A new conceptual mathematical model can be used to explain the relationship between pressures and flow at the venous outflow from the cranium.

Blood Flow Velocity↗