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Biomedical subjects

D I Graham

Publications and source records attributed to D I Graham.

At least 19 recordsLinked to original sources
PubMed1992

Inhibition of nitric oxide synthesis does not reduce infarct volume in a rat model of focal cerebral ischaemia.

The effect of the nitric oxide (NO) synthesis inhibitor Ng-nitro-L-arginine methylester (L-NAME) on ischaemic brain damage was determined in a rat model of focal cerebral ischaemia. Ischaemia was induced by permanent occlusion of the left middle cerebral artery (MCA) and infarction assessed 4 h post-occlusion by quantitative histopathology. L-NAME (30 mg/kg s.c.), administered 30 min pre- and 30 min post-MCA occlusion, did not significantly alter the volume of ischaemic damage in the cerebral hemisphere, neocortex or caudate nucleus compared with saline controls. This result provides no support for the view that NO generation is a key component in the post-ischaemic cascade leading to acute neuronal death.

Animals↗
PubMed1992

The cerebrovascular response to experimental lateral head acceleration.

A number of microvascular changes, such as the development of astrocyte lucency, increased endothelial pit/vesicle activity, development of crater like lesions, and endothelial microvilli have been reported after injury to the brain. Lateral head acceleration in the non-human primate, however, still provides the best experimental model for human diffuse axonal injury. No attempt has yet been made to document the spatial extent or time course of the microvascular response to acceleration injury to the head. We have examined the brains of baboons 1, 4, 6, and 12 h and 7 days after acceleration injury to the head to analyse the microvascular response. In the experimental animals there was a short-term rise in intracranial pressure followed by a long-term resolution, and a reduction in both mean arterial blood pressure and cerebral perfusion pressure which, however, never dropped below 75% of baseline for more than 5 min after injury in any animal. We found evidence for extravasation of blood in a small number of blood vessels in all parts of the brain. Interendothelial tight junctions are not disrupted. Pit/vesicle activity rises in the 1st h in the occipital cortex, but not until 4 h in the frontal cortex, and remains elevated for at least 7 days. There is little change in the thalamus. Development of microvilli is most rapid in the frontal cortex with peak values at 1 h, but slower in the thalamus and occipital cortex where peak values are only obtained at 6 h. Highest numbers of microvilli occur in parasagittal regions of the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Acceleration↗
PubMed1992

Changes in the choroid plexus, responses by intrinsic epiplexus cells and recruitment from monocytes after experimental head acceleration injury in the non-human primate.

We have examined, by scanning and transmission electron microscopy, morphological changes in the choroid plexus of the lateral ventricles of the non-human primate brain after lateral head acceleration. We demonstrate passage of plasma and blood cells either through tears in blood vessels and the choroidal epithelium, or through the cells of the choroidal epithelium, 20 min after injury, together with morphological changes in that epithelium. At 3 and 4 h small cells with a reniform nucleus accumulate in the connective tissue core of the choroid plexus. We suggest that these are monocytes. At 6 and 12 h cells can be seen in enlarged intercellular spaces within the choroidal epithelium. These cells possess surface ruffles and we suggest that they are monocytes differentiating into macrophages and epiplexus cells. Further evidence for transepithelial migration of monocytes/macrophages is obtained at 7 days. However, at 28 days all blood has been removed from the surface of the choroid plexus and epiplexus cells possess an appearance typical of that in uninjured animals. The possible sources of epiplexus cells are discussed with reference to studies of responses after brain insult and of development. We have obtained no evidence in support of emperipolesis by monocytes through the choroidal epithelium. We suggest that monocytes/macrophages migrate, via an intercellular route, to differentiate into epiplexus cells, thus providing additional numbers of epiplexus cells after head injury.

Acceleration↗
PubMed1992

Release of endogenous adenosine and its metabolites by the activation of NMDA receptors in the rat hippocampus in vivo.

1. The effects of N-methyl-D-aspartate (NMDA), KCl, and veratridine on the release of endogenous adenosine and its metabolites, inosine and hypoxanthine, from the rat hippocampus have been studied by in vivo microdialysis. 2. In the hippocampus of rats anaesthetized with urethane the adenosine level reached a stable state estimated at 0.93 microM during the first 2 h after the implantation of the dialysis probe. NMDA (50 microM to 25 mM) in the perfusate evoked a concentration-dependent release of adenosine, inosine and hypoxanthine with an EC50 of 180 microM. The release was reduced by 93% by the specific NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (2-AP5) at 200 microM, indicating an NMDA receptor-mediated process. In addition, the 100 mM KCl-evoked release of adenosine was also substantially reduced by 77% by 2-AP5, suggesting that a large component of the K(+)-evoked release is NMDA-receptor-mediated. 3. Perfusion with zero-Ca2+ artificial cerebrospinal fluid attenuated the NMDA-evoked release of adenosine only by 16% (not significant) but depressed the K(+)-evoked release by 62%, indicating that most of the NMDA-evoked release is directly receptor-mediated, whereas a large component of the K(+)-evoked release could be via the release of an excitatory amino acid acting at the NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1992

Diffuse axonal injury caused by assault.

The case reports of 50 fatal head injuries caused by assault and managed at the Institute of Neurological Sciences, Glasgow, were reviewed. Fifteen cases had diffuse axonal injury. Diffuse axonal injury is a well recognised type of brain damage brought about by a head injury, usually as a result of a road traffic accident or fall from a height. It does not seem to be widely appreciated that it may also occur as a result of an assault. This has important medicolegal implications.

Adolescent↗
PubMed1979

Effects of increasing arterial pressure on cerebral blood flow in the baboon: influence of the sympathetic nervous system.

The influence of stimulation of the cervical sympathetic chain on the response of cerebral blood flow to hypertension induced by the intravenous infusion of angiotensin was studied in anaesthetised baboons. Cerebral blood flow was measured by the intracarotid 133Xenon injection technique. Possible lesions of the blood-brain barrier were studied by injecting Evans blue towards the end of the experiment and ischaemic brain damage was assessed following perfusion fixation. In a control group of five baboons blood flow increased by 53 +/- 9% (mean +/- S.E.) from the base line values in the arterial pressure range 130-159 mm Hg. In four baboons subjected to unilateral sympathetic stimulation flow increased by 16 +/- 4% in the same pressure range. In three baboons subjected to bilateral sympathetic stimulation there were no significant increases in flow until the arterial pressure had increased above 159 mm Hg. Disruption of the blood-brain barrier in the parietooccipital regions was only seen in the control animals but not in the stimulated baboons. Ischaemic brain damage was not observed with the exception of one small lesion in a single stimulated baboon. These findings provide strong support for the observations of Bill and Linder (1976) that activation of the cervical sympathetic can modify the level at which breakthrough of cerebral blood flow occurs in association with systemic hypertension.

Angiotensin II↗
PubMed1979

Diffuse cerebral ischemia in the cat: III. Neuropathological sequelae of severe ischemia.

The neuropathological consequences of sever diffuse cerebral ischemia were investigated in an animal model in which postischemic alterations of regional brain blood flow and energy metabolism had been previously characterized. Pentobarbital-anesthetized cats received either 15 or 30 minutes of ischemia produced by basilar artery and bilateral carotid artery occlusions plus mild hypotension; this was followed by 60 to 90 minutes of normotensive recirculation. The brains were perfusion-fixed for light microscopy. Both insult durations resulted in unequivocal ischemic cell change affecting neurons of the cerebral neocortex, striatum, thalamus, and hippocampus and portions of the rostral brainstem. Animals with 30 minutes of prior ischemia differed from those with 15 minutes of ischemia in showing a more apparent regional accentuation of ischemic change in the parasagittal cortical gyri--the sites of previously documented focal postischemic heterogeneities of blood flow and metabolism. In other respects, however, the overall distribution and spectrum of severity of the ischemic alterations were similar for the two insult durations. These data support the view that significant permanent neuronal injury may result from a period of cerebral ischemia as brief as 15 minutes.

Animals↗
PubMed1979

Glial fibrillary acidic protein (GFAP): purification from human fibrillary astrocytoma, development and validation of a radioimmunoassay for GFAP-like immunoactivity.

The extraction and purification of glial fibrillary acidic protein (GFAP) from human fibrillary cerebellar astrocytoma is described. Using an immunoperoxidase method, antisera raised to the protein showed specific staining of astrocytes in normal spinal cord and in tumours of astrocytic origin. A double antibody radioimmunoassay for GFAP in tissue extract was developed, the detection limit of the assay being 360 pg. Extracts of tissues other than brain or spinal cord did not cross-react significantly in the assay, neither did purified preparations of myelin basic and S-100 proteins. Levels of GFAP in normal CNS tissue were higest in spinal cord (1370 microgram/g wet weight) but a level of 3050 microgram/g wet weight was detected in a fibrillary astrocytoma.

Astrocytes↗
PubMed1979

Brain damage complicating septic shock: acute haemorrhagic leucoencephalitis as a complication of the generalised Shwartzman reaction.

The neuropathological findings in six patients who developed neurological signs after the onset of "septic shock" caused by Gram-negative septicaemia are described. The changes in the brains were characteristic of acute haemorrhagic leucoencephalitis, and there was evidence, particularly in the kidneys, of disseminated intravascular coagulation with tubular necrosis and, in some, appearances indistinguishable from membrano-proliferative glomerulonephritis. It is agreed that acute haemorrhagic leucoencephalitis is another manifestation of a generalised Shwartzman reaction, and it is suggested that activation of complement is the final common pathway that produces tissue damage in the brain and kidney.

Adult↗
PubMed1979

Delayed effects of subarachnoid haemorrhage on cerebral metabolism and the cerebrovascular response to hypercapnia in the primate.

A technique is described for the production of subarachnoid haemorrhage in baboons and their subsequent recovery for chronic study of cerebrovascular reactivity. The baboons make complete neurological recoveries but the response of their cerebral circulation to hypercapnia is impaired one week later. Baseline values of cerebral blood flow and of cerebral oxygen consumption are unaffected at this time. There is no evidence of hypoxic brain damage.

Animals↗
PubMed1979

Late effects of subarachnoid haemorrhage on the response of the primate cerebral circulation to drug-induced changes in arterial blood pressure.

The ability of the cerebral circulation to maintain a constant level of cerebral blood flow with halothane-induced hypotension and angiotensin-induced hypertension was found to be impaired one week after subarachnoid haemorrhage in the baboon. No evidence of hypoxic brain damage was found. The clinical significance of these findings is discussed.

Angiotensin II↗
PubMed1979

Computerised tomography after recent severe head injury in patients without acute intracranial haematoma.

Sixty patients with severe head injury who did not have an acute intracranial haematoma on CAT scanning are reviewed. The scans are correlated with the level of consciousness at the time of scanning and with the outcome six months after injury. The initial scan was interpreted as being normal in 38% of the cases. In the remainder the most common abnormalities were small ventricles and areas of mixed increased and decreased density interpreted as contusions. All the patients with small ventricles were under 20 years of age. Postmortem examinations were undertaken on 15 of the 19 fatal cases. There was evidence of a high intracranial pressure in 12, cerebral contusions were absent or minimal in 10, there was diffuse immediate impact damage to white matter in six, and there was moderate or severe hypoxic damage in four.

Adult↗
PubMed1978

The smear technique in the diagnosis of neurosurgical biopsies.

This paper reviews 216 consecutive neurosurgical biopsies examined by the immediate smear technique, and the smear diagnoses are compared with the final diagnoses made on paraffin processed sections of the same material. Ninety three percent (93%) of the diagnoses were correct. The majority of errors were due to the incorrect classification of malignant tumours. The diagnosis of malignancy, however, was clearly established in all of these cases. The smear technique is suitable for application to material obtained at craniectomy, laminectomy, and also the small, soft pieces of tissue obtained by needle biopsy through a burr hole.

Biopsy↗
PubMed1978

Ischaemic brain damage in fatal non-missile head injuries.

The incidence and distribution of ischaemic brain damage in a consecutive series of 151 patients who died as a result of a non-missile head injury in the Institute of Neurological Sciences was determined on the basis of a comprehensive neuropathological and neurohistological examination. Ischaemic damage was identified in 138 cases (91%) even after excluding cases who only had necrosis and infarction related to contusions or fat embolism, and infarction in the brain stem of the type conventionally associated with raised intracranial pressure. The ischaemic damage was assessed as severe in 37 (27%), moderately severe in 59 (43%) and mild in 42 (30%), and in the 138 cases with ischaemic brain damage it was found more frequently in the hippocampus (122 cases; 81%), and in the basal ganglia (119 cases; 79%) than in the cerebral cortex (70 cases; 46%) and in the cerebellum (67 cases; 44%). There were statistically significant correlations between ischaemic brain damage and either an episode of hypoxia or of raised intracranial pressure. From the nature of the brain damage it seems likely that much of it was due to a reduction in the cerebral perfusion pressure. This study has shown that ischaemic brain damage is common after head injury, that at least a proportion of it is probably avoidable, and that it is more important as a cause of mortality and morbidity after head injury than has been hitherto realised.

Adolescent↗
PubMed1978

Effects of hypotension induced by halothane, on the cerebral circulation in baboons with experimental renovascular hypertension.

The effect of graded, progressive hypotension on the autoregulation of cerebral blood flow was studied in anaesthetized baboons with experimental renovascular hypertension. Graded hypotension was induced over a period of 5-6 h by the administration of increasing concentrations of halothane. In these chronically hypertensive animals cerebral blood flow remained constant until the mean arterial pressure had decreased to approximately 90 mm Hg. At mean arterial pressures of less than this value cerebral blood flow was pressure passive. At the completion of the investigation the brains were fixed by perfusion and submitted to neuropathological examination. Evidence of chronic hypertension and of ischaemic brain damage was found in every animal.

Animals↗
PubMed1978

Remote metastases from intracranial tumours.

A review of the primary tumours of the nervous system encountered over the past 16 years from the population of the west of Scotland uncovered only three tumours in which remote extracranial metastases had developed. In all three, there had been surgical intervention before the appearance of metastases. The findings in these patients are compared with those in other published accounts of this unusual complication.

Adult↗