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Biomedical subjects

J D Pickard

Publications and source records attributed to J D Pickard.

At least 163 records · Page 9Linked to original sources
PubMed1998

Indices for decreased cerebral blood flow control--a modelling study.

Time-dependent interactions between pressure, flow and volume of cerebral blood and cerebrospinal fluid were mathematically modelled. The model was designed to simulate blood inflow and storage, arteriolar and capillary blood circulation controlled by cerebral autoregulation, venous blood outflow and storage modulated by intracranial pressure, and cerebrospinal fluid production, storage and reabsorption. The software implementation of the model was used to calculate the response to a gradual decrease in cerebral perfusion pressure corresponding to either systemic hypotension or intracranial hypertension. We computed flow pulsatility index (PI) and short range correlation coefficients between systolic, diastolic and mean flow velocity (FVs,d,m) and mean cerebral perfusion pressure (CPP). In simulation, the changes in cerebral flow produced by intracranial hypertension and systemic hypotension were practically indistinguishable. The relationship between PI and CPP was reciprocal, independent of the state of autoregulation. The short range running correlation coefficients between FVs, FVm and CPP indicated both combined safe CPP range and preserved autoregulation, promising a clear clinical detection of "non-worsening" blood supply conditions. A similar procedure was applied to selected clinical data to illustrate the theoretical considerations.

Adolescent↗
PubMed1998

Hydrodynamic properties of hydrocephalus shunts.

Hydrodynamic properties of hydrocephalus shunts are not always properly characterized by the manufacturer. Therefore, the choice of the shunt should be made, by matching performance of the shunt to the disturbed profile of CSF circulation of a given patient. The aim of the present shunt evaluation study is to evaluates all types of shunts presently in use in the U.K. and make this information available to neurosurgeons. Ten most common models of valves have been tested to date: Medtronik PS Medical: Delta Valve, Flow Control Valves and Lumbo-Peritoneal Shunt, Heyer-Schulte: In-line, Low Profile and Pudenz Flushing Valve, Codman: Medos-Programmable, Hakim-Precision, Sophy Programmable Valve, Cordis Orbis-Sigma. Our results show the majority of valves have low hydrodynamic resistance (exception: PS Lumboperitoneal, Orbis-Sigma), which increase by 100-200% after connection of a long distal catheter. A few shunts with siphon-preventing mechanism (Delta, Hayer-Schulte Low Profile, Pudenz-Flushing) offer reasonable resistance to negative outlet pressures, however, these valves may be blocked by raised subcutaneous pressure. All programmable valves are susceptible to siphoning. Programmed settings may be changed by external magnetic field.

Cerebrospinal Fluid Pressure↗
PubMed1998

Comparison of the vasoconstrictor effects of rizatriptan and sumatriptan in human isolated cranial arteries: immunohistological demonstration of the involvement of 5-HT1B-receptors.

AIMS: We compared the vasoconstrictor effects of 5-HT with those of the selective 5-HT1B/1D-receptor agonists sumatriptan and rizatriptan in human isolated cranial (middle meningeal) arteries. In addition selective 5-HT1B- or 5-HT1D-receptor antibodies were used in combination with semiquantitative immunohistochemical techniques to compare the levels of expression of these receptors in human middle meningeal and coronary arteries. METHODS: Middle meningeal and coronary arteries were obtained (with consent) from either neurosurgical patients or donor hearts, respectively. Segments of middle meningeal artery were mounted in organ baths for isometric recording and cumulative concentration-effect curves to 5-HT, rizatriptan and sumatriptan were obtained. Frozen fresh sections of middle meningeal and coronary arteries were subjected to standard immunohistochemical techniques using specific 5-HT1B- or 5-HT1D-receptor primary antibodies and a radiolabelled secondary antibody. Data were subjected to analysis of variance (ANOVA) and nonlinear regression analysis. RESULTS: 5-HT, rizatriptan and sumatriptan were potent vasoconstrictors in human isolated middle meningeal artery (EC50 values=32, 90 and 71 nM, respectively). A significantly higher level of 5-HT1B-receptor immunoreactivity was detected in middle meningeal artery compared with coronary artery (ANOVA, F=7.95, DF=1,4, P<0.05). CONCLUSIONS: Rizatriptan and sumatriptan act selectively to cause vasoconstriction in human isolated middle meningeal artery and are 10-fold more potent than in human coronary artery. The higher level of expression of 5-HT1B-receptors in middle meningeal compared with coronary artery provides a pharmacological basis for the craniovascular selectively of both rizatriptan and sumatriptan.

Adult↗
PubMed1998

Posture-related overdrainage: comparison of the performance of 10 hydrocephalus shunts in vitro.

OBJECTIVE: Approximately 10 to 30% of shunt revisions may be attributed to posture-related overdrainage. The susceptibility of various hydrocephalus shunts to overdrainage of cerebrospinal fluid requires independent laboratory evaluation. METHODS: Shunts were tested in vitro by using precise computer-controlled equipment that was able to evaluate pressure-flow performance curves under various conditions. Hydrodynamic resistance and opening, closing, and operational pressures were evaluated for at least 28 days with normal (atmospheric) and decreased (-23 mm Hg, based on the International Standard Organization/Draft International Standard 7197 standard, which simulates conditions in upright body positions) outlet pressures. RESULTS: Ten different models of valves have been tested to date (Medtronic PS Medical Delta valve, flow-control valve, and lumboperitoneal shunt, Heyer-Schulte in-line, low-profile, and Pudenz flushing valves, Codman-Medos programmable and nonprogrammable valves, Sophy programmable valve, and Cordis Orbis-Sigma valve). The majority of these valves produced significantly negative (less than -10 mm Hg) average intracranial pressures in vertical body positions. In conjunction with nonphysiologically low hydrodynamic resistance (with the exception of the Orbis-Sigma valve, Medtronic PS Medical lumboperitoneal shunt, and Heyer-Schulte in-line valve), this may result in overdrainage related to body posture. The clinically reported rate of complications related to overdrainage is probably reduced by the long distal catheter, which increases the resistance of these valves by 100 to 200%. A few shunts (the Delta valve, low-profile valve, and Pudenz flushing valve with anti-siphon devices) offer reasonable resistance to negative outlet pressure, preventing complications related to overdrainage, but all valves with siphon-preventing devices may be blocked by increased subcutaneous pressure. CONCLUSION: Shunts without mechanisms preventing very low intracranial pressure in vertical body positions should be identified and avoided for patients likely to develop complications related to cerebrospinal fluid overdrainage.

Cerebrospinal Fluid Shunts↗
PubMed1998

Expression of endothelin(A) receptors in human gliomas and meningiomas, with high affinity for the selective antagonist PD156707.

OBJECTIVE: Endothelin (ET) immunoreactivity, ET production, and specific ET receptors have been identified in the brain. Changes in ET concentration or receptor expression have been implicated in the pathophysiological changes in vasospasm after subarachnoid hemorrhage and in cerebral neoplasia. In this study, we have characterized the ET(A) and ET(B) receptor subtypes present in human normal cerebral cortex (NCC) and two common central nervous system tumors, i.e., meningioma (MNG) and glioblastoma multiforme (GBM). A knowledge of the ET receptor subtypes present may provide a novel therapeutic target for newly developed ET antagonists. METHODS: Saturation, competition, and autoradiographic studies were performed with the subtype-specific radioligands 125I-PD151242 and 125I-BQ3020, to characterize the ET(A) and ET(B) receptors present in NCC, MNG, and GBM. RESULTS: NCC expresses high-affinity ET(A) receptors on pial and intraparenchymal vessels and high-affinity ET(B) receptors on glia and neurons. MNGs express mainly (85%) high-affinity ET(A) receptors in a diffuse pattern, whereas GBMs express high-affinity ET(A) receptors on the neovasculature and ET(B) receptors on the nonvascular elements. The ET antagonist PD156707 (Kd = 0.059 nmol/L) showed a higher affinity for the ET(A) receptor subtype than did bosentan (Kd = 1.1 nmol/L). CONCLUSION: ET(A) receptors are expressed in high concentrations in MNGs and in the vasculature of NCC and GBMs. The ET(A)-selective antagonist PD156707 may be of potential therapeutic value in vascular and neoplastic diseases of the central nervous system.

Autoradiography↗
PubMed1998

The management of minor traumatic brain injury.

Minor traumatic brain injury accounts for the majority of the one million head trauma attendances at A&E departments in the United Kingdom. Guidelines have been established listing criteria for skull films, admission to hospital, computed tomography, and neurosurgical consultation. These are currently undergoing revision and were the subject of a satellite symposium to the J Douglas Miller memorial meeting held in October 1996 in Edinburgh. In the East Anglia Region the current guidelines have been issued as memo-cards for A&E officers. The aim of admission is to observe for deterioration, predominantly caused by intracranial haematomas. The indicators for the development of such lesions are an impaired level of consciousness and presence of a skull fracture. Such patients should therefore undergo regular and frequent neurological observations, and be admitted for at least 12 hours. Following discharge, routine follow up should be considered to identify and treat patients with postconcussion symptoms and signs. The possible way forward for the management of these patients is adopting a greater emphasis on preventative aspects, and establishing, implementing, and auditing evidence based guidelines. Improved teaching in the form of formal induction seminars and computerised teaching aids is required, and a better understanding of the aetiology and treatment of the postconcussion syndrome.

Brain Injuries↗
PubMed1998

Jugular venous and arterial concentrations of serum S-100B protein in patients with severe head injury: a pilot study.

The objective of this study was to analyse the temporal course of the jugular venous-arterial gradient of S-100B protein after severe head injury and the correlation between the absolute concentrations of serum S-100B protein and outcome, CT findings, and clinical variables. Fifteen patients were included in this pilot study. All patients were treated according to a standard therapy protocol targeted to maintain cerebral perfusion pressure. The serum concentration of S-100 protein was measured daily for five consecutive days after injury by a monoclonal two site immunoluminometric assay. Nine patients showed favourable and six unfavourable outcome after 6 months with a mortality rate of 33% (five patients). The mean gradient between jugular venous and arterial blood was 8.2% (p<0.05). Patients showing an unfavourable outcome had significantly higher jugular venous or arterial S-100 values compared with those with a favourable outcome (jugular venous S-100B 2.78 microg/l v 1.22 microg/l, p<0.05; arterial S-100B 2.48 microg/l v 1.19 microg/l, p<0.05). All patients with an initial or secondary increase in S-100B value of >2 microg/l were found to have an unfavourable outcome. S-100B was found to be an independent predictor of outcome after severe head injury. The persisting increase of S-100B for three to five days even in patients with favourable outcome and no signs of secondary insults might reflect continuing damage to the blood-brain barrier or ongoing glial cell death.

Adolescent↗
PubMed1998

Cerebral perfusion pressure in head-injured patients: a noninvasive assessment using transcranial Doppler ultrasonography.

OBJECT: The authors studied the reliability of a new method for noninvasive assessment of cerebral perfusion pressure (CPP) in head-injured patients in which mean arterial blood pressure (ABP) and transcranial Doppler middle cerebral artery mean and diastolic flow velocities are measured. METHODS: Cerebral perfusion pressure was estimated (eCPP) over periods of continuous monitoring (20 minutes-2 hours, 421 daily examinations) in 96 head-injured patients (Glasgow Coma Scale score < 13) who were admitted to the intensive care unit. All patients were sedated, paralyzed, and ventilated. The eCPP and the measured CPP (ABP minus intracranial pressure, measured using an intraparenchymal microsensor) were compared. The correlation between eCPP and measured CPP was r=0.73; p < 10(-6). In 71% of the examinations, the estimation error was less than 10 mm Hg and in 84% of the examinations, the error was less than 15 mm Hg. The method had a high positive predictive power (94%) for detecting low CPP (< 60 mm Hg). The eCPP also accurately reflected changes in measured CPP over time (r > 0.8; p < 0.001) in situations such as plateau and B waves of intracranial pressure, arterial hypotension, and refractory intracranial hypertension. A good correlation was found between the average measured CPP and eCPP when day-by-day variability was assessed in a group of 41 patients (r=0.71). CONCLUSIONS: Noninvasive estimation of CPP by using transcranial Doppler ultrasonography may be of value in situations in which monitoring relative changes in CPP is required without invasive measurement of intracranial pressure.

Adolescent↗
PubMed1998

A multicenter trial on the efficacy of using tirilazad mesylate in cases of head injury.

OBJECT: The authors prospectively studied the efficacy of tirilazad mesylate, a novel aminosteroid, in humans with head injuries. METHODS: A cohort of 1120 head-injured patients received at least one dose of study medication (tirilazad or placebo). Eighty-five percent (957) of the patients had suffered a severe head injury (Glasgow Coma Scale [GCS] score 4-8) and 15% (163) had sustained a moderate head injury (GCS score 9-12). Six-month outcomes for the tirilazad- and placebo-treated groups for the Glasgow Outcome Scale categories of both good recovery and death showed no significant difference (good recovery in the tirilazad-treated group was 39% compared with the placebo group in which it was 42% [p=0.461]; death in the tirilazad-treated group occurred in 26% of patients compared with the placebo group, in which it occurred in 25% [p=0.750]). Subgroup analysis suggested that tirilazad mesylate may be effective in reducing mortality rates in males suffering from severe head injury with accompanying traumatic subarachnoid hemorrhage (death in the tirilazad-treated group occurred in 34% of patients; in the placebo group it occurred in 43% [p=0.026]). No significant differences in frequency or types of serious adverse events were shown between the treatment and placebo groups. CONCLUSIONS: Striking problems with imbalance concerning basic prognostic variables were observed in spite of the large population studied. These imbalances concerned pretreatment hypotension, pretreatment hypoxia, and the incidence of epidural hematomas. In future trials of pharmacological therapy for severe head injury, serious consideration must be given to alternative randomization strategies. Given the heterogeneous nature of head injury and the identification of populations that do relatively well with standard therapy, target populations with a higher risk for mortality and morbidity may be more suitable for clinical trials of such agents.

Adult↗
PubMed1997

Experience with the United Kingdom examinations in neurosurgery.

The UK Intercollegiate Specialty Board examination in Surgical Neurology was established in 1991 based on the experience of the original Royal College of Surgeons of Edinburgh Assessment in Surgical Neurology, an exit examination that was originally opposed both by surgery in general and by the younger neurosurgical community. Criteria for eligibility encompass both UK, EC and non-EC overseas graduates. Candidates must have completed satisfactorily their 4th year of a 6 year training programme, have personal experience with the more straightforward benign tumours, aneurysms and posterior fossa explorations, and be able to safely manage a conventional neurosurgical practice. The examination consists of a multiple choice question paper, clinical examination and three Vivas. A curriculum is under construction. Examinations are held twice per annum, and rotate between the four colleges. There are strict guidelines for the examiners. The pass rate is about 70%. All aspects of the examination continue to evolve and are carefully audited.

Clinical Competence↗
PubMed1997

Changes in transcranial Doppler flow velocity waveform following inhibition of nitric oxide synthesis. Experimental study in anaesthetised rabbits.

BACKGROUND: Analysis of the transcranial Doppler blood flow velocity (FV) waveform is used clinically to detect changes in cerebral haemodynamic profile. Such changes may be initiated both by alterations in microvascular resistance and in the tone of the cerebral arteries. METHODS: The role of endothelial mechanisms was investigated using inhibition of NO synthesis by systemic administration of NG-nitro-L-arginine methyl ester (L-NAME, 6 mg/kg) followed by simultaneous monitoring of both basilar artery FV and cerebrocortical microcirculation (laser Doppler flowmetry, LDF) in anaesthetised, ventilated rabbits over 60 minutes. RESULTS: Arterial blood pressure (AP) increased significantly (p < 0.01) above baseline level in the second minute following L-NAME and remained elevated until the end of experiment. Time average mean and systolic FV decreased immediately following L-NAME injection, with the statistically significant (p < 0.01) decrease from the third minute. Diastolic FV did not show such radical changes. LDF exhibited a slow decrease with time becoming significantly lower than baseline (p < 0.01) at 50 min. CONCLUSION: A gradual decrease in cortical microcirculation preceded by a rapid reaction recorded in the TCD waveform implies that an increase in the tone of the great cerebral arteries is the predominant phenomenon seen during the acute phase of NO synthase inhibition.

Animals↗
PubMed1997

A computing system for the clinical and experimental investigation of cerebrovascular reactivity.

We present a computing system for the recording and on-line analysis of analogue signals derived from bedside cerebrovascular monitors in different pathophysiological conditions. These include arterial blood pressure and oxygen saturation, end-tidal carbon dioxide concentration, cerebral blood flow velocities using transcranial Doppler ultrasonography, and concentration changes in cerebral oxy- and deoxyhaemoglobin from near infrared spectroscopy. Configuration and analysis adopts arithmetic expressions of different signal processing functions, various statistical properties for each signal, frequency spectrum analysis using fast Fourier transformation, and correlation/cross-correlation. The software offers off-line analysis of non-invasive tests of cerebrovascular reactivity. Several examples of clinical assessment of cerebrovascular reactivity are presented, including cerebral haemodynamic stress tests which employ carbon dioxide, acetazolamide, the breath holding test, leg cuff inflation and deflation, and transient carotid artery compression. Application within the experimental setting with induced haemorrhagic hypotension can also be used.

Cardiovascular Diseases↗
PubMed1997

Differential distribution of 5HT1D- and 5HT1B-immunoreactivity within the human trigemino-cerebrovascular system: implications for the discovery of new antimigraine drugs.

Sumatriptan, a 5HT1B/1D-receptor agonist, is clinically effective as an antimigraine agent. Its therapeutic action may result partly from vasoconstriction of excessively dilated cranial blood vessels (a 5HT1B-receptor mediated response). The antimigraine activity of sumatriptan may also result from inhibition of the release of vasoactive neuropeptides from trigeminal sensory fibres within the meninges. The identity of the 5HT1B/1D-receptor subtype mediating this effect is unknown. Using 5HT1D- and 5HT1B-receptor-specific antibodies we have demonstrated a differential distribution of these receptor subtypes within the human trigemino-cerebrovascular system. Only 5HT1B-receptor protein was detected on dural arteries. In contrast, only 5HT1D-receptor protein was detected on trigeminal sensory neurones including peripheral and central projections to dural blood vessels and to the medulla. Within the medulla 5HT1D-receptor protein was confined to discrete areas associated with the trigeminal sensory system. These findings have important implications for the design of new antimigraine drugs.

Adult↗
PubMed1997

Continuous assessment of the cerebral vasomotor reactivity in head injury.

OBJECTIVE: Cerebrovascular vasomotor reactivity reflects changes in smooth muscle tone in the arterial wall in response to changes in transmural pressure or the concentration of carbon dioxide in blood. We investigated whether slow waves in arterial blood pressure (ABP) and intracranial pressure (ICP) may be used to derive an index that reflects the reactivity of vessels to changes in ABP. METHODS: A method for the continuous monitoring of the association between slow spontaneous waves in ICP and arterial pressure was adopted in a group of 82 patients with head injuries. ABP, ICP, and transcranial doppler blood flow velocity in the middle cerebral artery was recorded daily (20- to 120-min time periods). A Pressure-Reactivity Index (PRx) was calculated as a moving correlation coefficient between 40 consecutive samples of values for ICP and ABP averaged for a period of 5 seconds. A moving correlation coefficient (Mean Index) between spontaneous fluctuations of mean flow velocity and cerebral perfusion pressure, which was previously reported to describe cerebral blood flow autoregulation, was also calculated. RESULTS: A positive PRx correlated with high ICP (r = 0.366; P < 0.001), low admission Glasgow Coma Scale score (r = 0.29; P < 0.01), and poor outcome at 6 months after injury (r = 0.48; P < 0.00001). During the first 2 days after injury, PRx was positive (P < 0.05), although only in patients with unfavorable outcomes. The correlation between PRx and Mean index (r = 0.63) was highly significant (P < 0.000001). CONCLUSION: Computer analysis of slow waves in ABP and ICP is able to provide a continuous index of cerebrovascular reactivity to changes in arterial pressure, which is of prognostic significance.

Adolescent↗
PubMed1997

Hydrodynamic properties of hydrocephalus shunts: United Kingdom Shunt Evaluation Laboratory.

BACKGROUND: Although about 80% of properly diagnosed patients with hydrocephalus improve after implantation of any model of shunt, the remaining 20% may develop further complications because of inadequate shunt performance. Therefore, hydrocephalus shunts require careful independent laboratory evaluation. METHOD: Computer supported shunt testing, based on the new International Standard Organisation directives, characterises various aspects of pressure-flow performance of shunts such as variability with time, susceptibility to reflux, siphoning, temperature related behaviour, external pressure, the influence of a strong magnetic field (for example, MRI), presence of pulsation in differential pressure, particles in drained fluid, etc. RESULTS: Seven different models of valves, representing most common constructions, have been tested so far. Most contemporary valves have a hydrodynamic resistance which is too low. 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%. Most shunts are very sensitive to the presence of air bubbles and small particles in drained fluid. Few shunt models offer reasonable resistance to negative outlet pressure, preventing complications related to overdrainage. Valves with an antisiphon device may be blocked by raised subcutaneous pressure. All programmable valves are susceptible to overdrainage in an upright position. CONCLUSION: The behaviour of a valve during such testing is of immediate relevance to the surgeon and may not be adequately described in the manufacturer's product information.

Cerebrospinal Fluid Shunts↗
PubMed1997

Contribution of mathematical modelling to the interpretation of bedside tests of cerebrovascular autoregulation.

OBJECTIVES: Cerebral haemodynamic responses to short and longlasting episodes of decreased cerebral perfusion pressure contain information about the state of autoregulation of cerebral blood flow. Mathematical simulation may help to elucidate which of the indices, that can be derived using transcranial Doppler ultrasonography and trends of intracranial pressure and blood pressure, are useful in clinical tests of autoregulatory reserve. METHODS: Time dependent interactions between pressure, flow, and volume of cerebral blood and CSF were modelled using a set of non-linear differential equations. The model simulates changes in arterial blood inflow and storage, arteriolar and capillary blood flow controlled by cerebral autoregulation, venous blood storage and venous outflow modulated by changes in ICP, and CSF storage and reabsorption. The model was used to simulate patterns of blood flow during either short or longlasting decreases in cerebral perfusion pressure. These simulations can be considered as clinically equivalent to a short compression of the common carotid artery, systemic hypotension, and intracranial hypertension. Simulations were performed in autoregulating and non-autoregulating systems and compared with recordings obtained in patients. RESULTS: After brief compression of the common carotid artery, a subsequent transient hyperaemia can be interpreted as evidence of intact autoregulation. During longlasting sustained hypoperfusion, a gradual increase in the systolic value of the blood flow velocity waveform along with a decrease in the diastolic value is specific for an autoregulating cerebrovascular system. CONCLUSION: Modelling studies help to interpret both clinical and experimental cerebral haemodynamic phenomena and their dependence on the state of autoregulation.

Blood Flow Velocity↗