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Biomedical subjects

J D Pickard

Publications and source records attributed to J D Pickard.

At least 19 recordsLinked to original sources
PubMed1992

Blood flow in portal systems with special reference to the rat pituitary gland.

Regional pituitary blood flow has been studied in adult female Fischer 344 rats by [14C]iodoantipyrine autoradiography. A general mathematical solution has been derived to allow the calculation of blood flow in the second compartment of a portal system and the proportion of blood "shunted" through the first compartment without exposure to tissue uptake from a knowledge of (a) the volume ratios of the two compartments, (b) the tissue tracer uptakes of the two compartments, and (c) the arterial tracer concentration with respect to time of a freely diffusible tracer. Significant diffusion limitation and/or arteriovenous shunting has been demonstrated in the neurohypophysis, suggesting that the majority of incoming blood is "shunted" unchanged to the adenohypophysis. The mean value of the shunt is 89% (range of 84-93%) for the median eminence and lies between 72% (range of 52-82%) and 73% (range of 59-81%) for the posterior pituitary. Neurohypophysial flow rates of 1.20 (range of 0.99-1.55) ml g-1 min-1 for the median eminence and 1.68 (range of 0.83-3.53) ml g-1 min-1 for the posterior pituitary were measured. These values represent "tissue-available" (nonshunted) flow; estimated mean total (shunted plus nonshunted) neurohypophysial flow rates were 11.7 (range of 9.5-17.5) ml g-1 min-1 for the median eminence and 6.1 (range of 3.1-8.9) ml g-1 min-1 (minimum) for the posterior pituitary. Adenohypophysial blood flow is heterogeneous. In the long portal territory, the flow rate was 1.18 (range of 0.95-1.75) ml g-1 min-1 but short portal territory flow calculation is complicated by an unquantifiable nonportal venous drainage; using the natural limits of zero and 100% gives a minimum adenohypophysial flow rate of 1.42 (range of 0.76-2.07) ml g-1 min-1 and a maximum value of 1.97 (range of 1.03-2.82) ml g-1 min-1.

Algorithms↗
PubMed1992

Experimental aspects of cerebrospinal hemodynamics: the relationship between blood flow velocity waveform and cerebral autoregulation.

The dynamic relationships among mean flow velocity, its pulsatile amplitude (FVa), cortical cerebral blood flow (CBF), and cerebral perfusion pressure (CPP) were studied in normal rabbits and rabbits with subarachnoid hemorrhage using 8-MHz pulsed transcranial Doppler ultrasound and hydrogen clearance under conditions of systemic hypotension and intracranial hypertension. A two-slope relationship was observed between FVa and CPP with a break point that correlated closely with the lower limit of CBF autoregulation in each animal. Below this CPP break point, FVa varied directly with CPP, and above the break point FVa varied inversely with CPP. In this experimental model, an inverse correlation between FVa and CPP indicates intact CBF autoregulation, whereas loss of that correlation implies exhaustion of autoregulatory reserve. Simultaneous recording and computation of FVa, CPP, and the correlation coefficient between FVa and CPP may be a means of monitoring CBF autoregulation in clinical practice.

Animals↗
PubMed1991

Eicosanoid production by brain tumours in vivo--evidence for intracranial compartmentation.

Brain tumours produce prostaglandins in vitro; their in vivo production has been studied by determining the levels of prostaglandin F2 alpha, prostaglandin E2, 6-ketoprostaglandin F1 alpha and thromboxane B2 in tumour cyst fluid and ventricular CSF taken from 21 patients with a variety of intracranial tumours. The levels were high in tumour cyst fluid but there was no overall increase in ventricular CSF. Hence, brain tumours do not produce a consistent pattern of abnormality of eicosanoid concentrations in the ventricular CSF that would be useful for diagnosis. If brain tumours produce excess quantities of these prostaglandins in vivo as they do in vitro, these prostaglandins may be rapidly cleared by the cerebral microvasculature unless compartmentalized within a tumour cyst.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

The effects of hyponatraemia and subarachnoid haemorrhage on the cerebral vasomotor responses of the rabbit.

Impairment of cerebral autoregulation and development of hyponatraemia are both implicated in the pathogenesis of delayed cerebral ischaemia and infarction following subarachnoid haemorrhage (SAH) but the pathophysiology and interactions involved are not fully understood. We have studied the effects of hyponatraemia and SAH on the cerebral vasomotor responses of the rabbit. Cerebrovascular reactivity to hypercapnia and cerebral autoregulation to trimetaphan-induced hypotension were determined in normal and hyponatraemic rabbits before and 6 days after experimental SAH produced by two intracisternal injections of autologous blood. Hyponatraemia (mean plasma sodium of 119 mM) was induced gradually over 48 h by administration of Desmopressin and intraperitoneal 5% dextrose. Sham animals received normal saline. The cerebrovascular reactivity (% change +/- SD in cortical CBF/mm Hg PaCO2, measured by hydrogen clearance) of hyponatraemic (4.8 +/- 3.0%) and SAH (1.3 +/- 2.0%) animals was significantly less (p less than 0.05) than control (11.6 +/- 4.0%) and sham (8 +/- 2.0%) animals, whereas the reactivity of hyponatraemic-SAH animals was preserved (9.8 +/- 6.0%). Hyponatraemia and SAH alone each significantly impaired CBF autoregulation but their combined effects were not additive. Systemic hyponatraemia impairs normal cerebral vasomotor responses but does not augment the effects of experimental SAH in the rabbit.

Animals↗
PubMed1991

Association of hypovolemia after subarachnoid hemorrhage with computed tomographic scan evidence of raised intracranial pressure.

Hypovolemic patients are more likely to suffer delayed cerebral ischemia and infarction after a subarachnoid hemorrhage (SAH). Prompt recognition and correction of hypovolemia may improve the outcome. We have identified computed tomographic (CT) scan findings that increase the probability of a patient presenting with hypovolemia soon after an SAH. The plasma volume (PV) of 25 patients admitted within 96 hours of an SAH was measured using radioiodinated serum albumin. The normal PVs were measured in an outpatient setting 6 months later or predicted from their total body water. Nine patients (36%) were found to be hypovolemic, defined as a fall in PV exceeding 10% of the normal PV (mean fall, 18 +/- 2%). Sixteen patients were normovolemic or hypervolemic (mean PV, +9 +/- 2%). The basal cisterns were compressed or obliterated on the CT scans of all hypovolemic patients compared with 12.5% of normovolemic patients (chi-square, 14.52; P less than 0.01). The probabilities of a patient being hypovolemic if the CT scan indicated raised intracranial pressure were high: hydrocephalus, P = 0.80; compression of the basal cisterns, P = 0.82; and compression of the basal cisterns associated with intracerebral hematoma or midline shift, P = 1.00. Patients with an SAH and radiological evidence of raised intracranial pressure should be considered at particular risk for systemic hypovolemia.

Adult↗
PubMed1991

Cerebral blood flow in the anaesthetized immature sheep fetus and the response to hypercapnia.

Regional cerebral blood flow (CBF) has been measured in eight anaesthetized, exteriorized, fetal sheep between 58 and 62 days gestation; four were controls, four were hypercapnic (PaCO2 = 78 +/- 5 mmHg, mean +/- S.E.M.). Blood flow values were calculated from quantitative autoradiography following the infusion of [14C]iodoantipyrine into a cannulated fetal placental vein, for the cerebellum, medulla, and five layers of the developing neocortex: cortical plate (CP), subplate zone (SP), intermediate zone (IZ), subventricular zone (SV), and the ventricular zone (VZ). The highest control CBF rates were recorded in the cortical plate (49.3 +/- 7.4 ml min-1 (100 g)-1, mean +/- S.E.M., posterior cortex) and in the ventricular zone (40.5 +/- 4.8, posterior cortex), which at this stage of development are the regions of greatest cell density. The lowest CBF rates were recorded in the subplate zone (23.8 +/- 6.8, anterior cortex) and in the intermediate zone (23.4 +/- 7.6, anterior cortex), which are the regions of lowest cell density. Experimentally induced hypercapnia increased CBF in all brain regions and enhanced the regional pattern of flow. The results provide evidence that CBF in the immature fetal sheep brain (at 58-62 days gestation) is heterogeneous under both control and hypercapnic conditions (especially in the neocortex). Blood vessels of the fetal sheep brain at this early stage of development are clearly responsive to CO2.

Animals↗
PubMed1990

Steps towards cost-benefit analysis of regional neurosurgical care.

OBJECTIVE: To determine the cost of averting death or severe disability by neurosurgical intervention. DESIGN: Retrospective analysis of one year's admissions for neurosurgery; comparison of outcome with expected outcome in the absence of neurosurgical intervention and with the cost of neurosurgery. SETTING: Wessex Neurological Centre. PATIENTS: 1026 Patients were admitted to the neurosurgical service in 1984. Of 1185 admissions, 978 case records were available and outcome was known in 919. MAIN OUTCOME MEASURES: Outcome was assessed with the Glasgow outcome scale, modified as necessary, from the case notes, or by letter follow up to the general practitioner. Expected outcomes for each of the 54 diagnoses were derived from both published reports where available and an expert panel of 18 consultant neurosurgeons. The cost of the neurosurgical service for 1983-4 was known from a separate study and the cost per patient was calculated using the length of stay. RESULTS: The cost of neurosurgery in 1983-4 was 1.8 million pounds. In all, 243 deaths or severe disabilities were estimated to have been averted at an average cost of 7325 pounds (range 5000 pounds to 70,000 pounds). The overall cost per quality adjusted life year (QALY) was 350 pounds (range 34 pounds to greater than 400,000 pounds). The cost of long term care for severely disabled survivors is at least 18-fold greater than the cost of neurosurgical intervention to avert such disability. CONCLUSIONS: In Britain neurosurgery is not expensive in comparison with the costs and benefits of other areas of medicine, and the cost per QALY is unexpectedly low except for severe diffuse head injury, malignant brain tumors, and cerebral metastases. The neurosurgical budget should be assessed in the context of managing a patient in hospital and subsequently in the community.

Brain Diseases↗
PubMed1990

Effect of hydrocephalus on prostaglandins and thromboxane B2 in ventricular cerebrospinal fluid.

The concentrations of prostaglandin F2 alpha, prostaglandin E2, 6-ketoprostaglandin F1 alpha (prostacyclin metabolite), and thromboxane B2 were assayed in ventricular cerebrospinal fluid obtained from 28 patients with hydrocephalus (17 obstructive, 11 communicating). Seven patients received dexamethasone or hydrocortisone on the day of sampling. No patient received nonsteroidal anti-inflammatory compounds for 48 hours before sampling. The median values did not differ significantly between the two types of hydrocephalus or from the concentrations in lumbar cerebrospinal fluid obtained from patients without intracranial pathology during lumbar myelography for possible lumbar disc disease. Hence, there is no evidence that eicosanoids accumulate in the ventricles in hydrocephalus, and it is unlikely that they have a significant role in its symptomatology.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

The relationship between intracranial pressure and tympanic membrane displacement.

Transmission of intracranial pressure (ICP) to the perilymph of the cochlea may occur via the cochlear aqueduct and possibly other routes. Indirect measurement of perilymphatic pressure may be investigated by observing tympanic membrane (TM) displacement during stapedial reflex contraction. In a previous study we investigated the effects of changes in ICP on perilymphatic fluid pressure in three patients who underwent ventriculo/lumbar-peritoneal shunt operations. The TM displacement technique proved extremely sensitive and revealed marked changes in cochlear fluid pressure brought about by changes in ICP (Marchbanks et al., 1987). The study has been extended to 58 patients with hydrocephalus, intracranial tumours and other neurological conditions associated with abnormal ICP. Significant differences in the TM displacement were found between patients with raised and normal ICP. We have shown that changes in ICP can affect the hydrostatic pressure of the cochlea and influence the peripheral auditory system. The finding that ICP can be correlated with TM displacement strengthens the association between an abnormal TM displacement and abnormal cochlear hydrostatic status, irrespective of cochlear aqueduct patency. We suggest that the TM displacement technique provides a useful non-invasive method for the assessment of perilymphatic fluid pressure.

Acoustic Stimulation↗
PubMed1990

Transcranial Doppler ultrasound studies of cerebral autoregulation and subarachnoid hemorrhage in the rabbit.

The authors describe a method for Doppler ultrasound recording of flow velocity in the basilar artery of normal rabbits and rabbits with experimental subarachnoid hemorrhage (SAH). With this transcranial Doppler (TCD) model, clinical assumptions regarding flow velocity/cerebral blood flow (CBF) relationships, autoregulatory responses, and Doppler spectral waveform analysis can be tested under controlled conditions and compared with established methods of CBF measurement (hydrogen clearance). The time course of changes in flow velocity following SAH (cerebral vasospasm) is successfully demonstrated using the experimental TCD method. There are significant differences in the flow velocity and CBF responses to hypercapnia, hypocapnia, and trimethaphan-induced hypotension which indicate that TCD cannot be considered a simple alternative to CBF measurement for the study of cerebrovascular reactivity and cerebral autoregulation.

Analysis of Variance↗
PubMed1989

Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial.

OBJECTIVE: To determine the efficacy of oral nimodipine in reducing cerebral infarction and poor outcomes (death and severe disability) after subarachnoid haemorrhage. DESIGN: Double blind, placebo controlled, randomised trial with three months of follow up and intention to treat analysis. To have an 80% chance with a significance level of 0.05 of detecting a 50% reduction in an incidence of cerebral infarction of 15% a minimum of 540 patients was required. SETTING: Four regional neurosurgical units in the United Kingdom. PATIENTS: In all 554 patients were recruited between June 1985 and September 1987 out of a population of 1115 patients admitted with subarachnoid haemorrhage proved by the results of lumbar puncture or computed tomography, or both. The main exclusion criterion was admission to the neurosurgical units more than 96 hours after subarachnoid haemorrhage. There were four breaks of code and no exclusions after entry. One patient was withdrawn and in 130 treatment was discontinued early. All patients were followed up for three months and were included in the analysis, except the patient who had been withdrawn. INTERVENTIONS: Placebo or nimodipine 60 mg was given orally every four hours for 21 days to 276 and 278 patients, respectively. Treatment was started within 96 hours after subarachnoid haemorrhage. END POINTS: Incidence of cerebral infarction and ischaemic neurological deficits and outcome three months after entry. MEASUREMENTS: Demographic and clinical data, including age, sex, history of hypertension and subarachnoid haemorrhage, severity of haemorrhage according to an adaptation of the Glasgow coma scale, number and site of aneurysms on angiography, and initial findings on computed tomography were measured at entry. Deterioration, defined as development of a focal sign or fall of more than one point on the Glasgow coma scale for more than six hours, was investigated by using clinical criteria and by computed tomography, by lumbar puncture, or at necropsy when appropriate. All episodes of deterioration and all patients with a three month outcome other than a good recovery were assessed by a review committee. MAIN RESULTS: Demographic and clinical data at entry were similar in the two groups. In patients given nimodipine the incidence of cerebral infarction was 22% (61/278) compared with 33% (92/276) in those given placebo, a significant reduction of 34% (95% confidence interval 13 to 50%). Poor outcomes were also significantly reduced by 40% (95% confidence interval 20 to 55%) with nimodipine (20% (55/278) in patients given nimodipine v 33% (91/278) in those given placebo). CONCLUSIONS: Oral nimodipine 60 mg four hourly is well tolerated and reduces cerebral infarction snd improves outcome after subarachnoid haemorrhage.

Administration, Oral↗
PubMed1989

The uptake of [14C]deoxyglucose into brain of young rats with inherited hydrocephalus.

The effect of hydrocephalus on cerebral glucose utilization as reflected by deoxyglucose uptake has been examined in rats with inherited hydrocephalus at 10, 20, and 28 days after birth using a semiquantitative method. Injection of [14C]deoxyglucose intraperitoneally was followed by freezing the brain, sectioning, and quantitative autoradiography of 10 brain regions. Brain [14C] concentration, cortical thickness, and plasma glucose concentrations were measured. Maximal thinning of the cerebral cortex had already occurred by 10 days after birth, although obvious symptoms such as gait disturbance developed after 20 days. In control rats, the cerebral isotope concentration was lower and more homogeneous at 10 days than at 20 or 28 days, which may be a reflection of the use of metabolic substrates other than glucose in younger animals. In order to make comparisons between control and hydrocephalic groups, tissue isotope concentrations were normalized to cerebellar cortex which was not affected by the hydrocephalus at any age. In hydrocephalic rats at 10 and 20 days, the concentration of [14C] was lower in all areas except the inferior colliculi and pons but the reduction was only significant in the sensory-motor cortex at 10 days and in the caudate nuclei at 20 days. By 28 days after birth, all areas except the cerebellum (six cortical regions, inferior colliculi, pons, and caudate) had significantly lower isotope concentrations in the hydrocephalic group. It is concluded that cerebral glucose metabolism is significantly reduced by 28 days after birth in H-Tx rats with congenital hydrocephalus and that less marked reductions occur prior to 28 days.

Aging↗
PubMed1989

Mean intracranial pressure monitoring by a non-invasive audiological technique: a pilot study.

Intracranial pressure is normally transmitted to the perilymph of the cochlea via the cochlear aqueduct. The relationship between perilymphatic pressure, indirectly measured by tympanic membrane displacement, and mean intracranial pressure defined either clinically or by direct measurement has been examined in 58 patients (aged 5-77 years), with hydrocephalus, benign intracranial hypertension, intracranial tumours, subarachnoid haemorrhage and head injuries. The most consistent results were obtained in young patients with hydrocephalus and benign intracranial hypertension. However, the technique was not suitable when the stapedial reflex was absent as a result of middle ear/brainstem dysfunction and did not reflect intracranial pressure when the cochlear aqueduct was not patent. This pilot study suggests that the tympanic membrane displacement technique may provide a useful non-invasive method for serial monitoring of intracranial pressure in young patients with hydrocephalus or benign intracranial hypertension.

Acoustic Impedance Tests↗