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Biomedical subjects

A J Strong

Publications and source records attributed to A J Strong.

At least 19 recordsLinked to original sources

The Maudsley Mentation test: a method for extended monitoring of mental status after aneurysmal subarachnoid hemorrhage.

A new scale for the repeated, rapid assessment of mental function in patients with subarachnoid hemorrhage is described. Its reproducibility is evaluated and early experience with its use in the intended clinical setting is reported. The test (Maudsley Mentation Test) proved to be more sensitive to fluctuations in cerebral functioning than existing measures of conscious level, and the results were reproducible among observers with different backgrounds (surgeons, nurses, and psychologists). The results suggest a relationship between performance on mentation testing and quality of outcome. The Maudsley Mentation Test is thought to offer a suitable measure with which to monitor patients during the acute phase of their illness to supplement clinical assessment and provide evidence of deterioration at an early stage. It is also potentially useful as an end point in acute protection and treatment studies.

Adult

Registration of MR and CT images for skull base surgery using point-like anatomical features.

We have developed a registration technique for combining magnetic resonance imaging (MRI) and computed tomography (CT) images of the skull base for use in surgical planning. The technique is based on user identification of point-like landmarks visible in both modalities. The combination of images involves a small amount of expert interaction, is relatively quick and preliminary evaluation indicates that it is accurate to within 1.5 mm. Registered or fused images can be viewed either on an image processing workstation, or fused images can be printed onto conventional film for convenience in clinical use. We present one patient in order to demonstrate the technique's indications and advantages.

Humans

Insulin protects cognitive function in experimental stroke.

There is evidence from in vitro systems that the extent of neuronal loss in acute central nervous system ischaemia can be reduced by manoeuvres which restrict availability of glucose to the ischaemic area. Experiments were designed to test whether hypoglycaemia induced with insulin is associated with improved behavioural outcome in a recovery model of stroke. Rats learned a maze task as a test of working memory, believed to be subserved by the hippocampus, and then had a period of cerebral ischaemia, followed by reperfusion. After an interval of 14 days they were tested on the same maze, where lesioned animals had very significant (p less than 0.0001) impairment of working memory, whereas lesioned and treated (2.0 u/kg-1 insulin, minimum single plasma glucose value: 3.1 mmol/l-1) animals were indistinguishable from control animals. It is concluded that a striking degree of protection can be obtained with levels of mild hypoglycaemia which may be acceptable and practicable for use in humans.

Animals

Simple peroperative antimicrobial chemoprophylaxis in elective neurosurgical operations.

From August 1981 to February 1982 postoperative infections due to different strains of penicillin-resistant Staphylococcus aureus occurred in 20 of 467 patients (4.3%) undergoing elective cranial and spinal operations. These infections were not attributable to defects in procedures or the theatre environment, therefore chemoprophylaxis was instituted. In the following 8 months, when patients were given penicillin G and sulphadiazine for 5 days commencing immediately postoperatively, S. aureus infections occurred in five of 579 patients (0.9%). In a subsequent randomized uncontrolled study, infections occurred in six of 265 patients receiving penicillin (2.3%), three of 270 receiving penicillin and sulphadiazine (1.1%) and one of 45 receiving erythromycin (2.2%) immediately postoperatively for 5 days. In a further study in which 587 patients received penicillin for 5 days commencing immediately preoperatively, infections due to S. aureus occurred in six (1.1%). Infections due to gram-negative organisms were seen in five (0.4%) of 1167 patients in the two uncontrolled studies.

Drug Therapy, Combination

Changes in vascular and metabolic reactivity as indices of ischaemia in the penumbra.

The reactivities of cerebral cortical blood flow (hydrogen clearance) and of compensated NADH fluorescence to local cortical electrical stimulation were examined on the marginal gyrus before and after transorbital occlusion of the middle cerebral artery in cats. Prestimulus cerebral blood flow (CBF) was 38.2 +/- 12.9 (SD) ml 100 g-1 min-1 and fell to 19.8 +/- 11.1 following occlusion (p less than 0.02). Peak hydrogen clearance rate (percent increase above prestimulus clearance) was 81.6 +/- 53.6 and fell to 19.9 +/- 29.8 after middle cerebral artery occlusion (p less than 0.01). Steady-state NADH fluorescence rose from 33.5 +/- 10.7 to 40.5 +/- 17.6% full-scale deflection following MCAO (p less than 0.01). Latency from stimulus to maximal fluorescence depression in response to cortical stimulation increased from 12.2 +/- 8.2 to 22.1 +/- 11.9 s (p less than 0.01). Hyperaemic responses at anteromedial sites on the marginal gyrus significantly exceeded those at posterolateral sites. The results are interpreted as indicating early ischaemic metabolic change; however, the presence of residual vasodilator responses to stimulation suggests that flow reduction and early ischaemic change in the territory studied are not simply due to inadequate collateral input, but may also reflect deafferentation or functional suppression. The possible significance of diminished vascular reactivity in the penumbra as a cause of increased vulnerability to extracellular release of excitatory amino acids is discussed.

Animals

A double-radionuclide autoradiographic method using N-isopropyl-iodoamphetamine for sequential measurements of local cerebral blood flow.

A double-radionuclide autoradiographic method has been assessed for sequential determinations of local CBF (LCBF). It is based on two successive intravascular injections of N-isopropyl-p-iodoamphetamine (IMP) labelled with different radionuclides, whose concentrations can later be differentiated in the same tissue section using double-radionuclide autoradiography. Previous studies suggested that the distribution of IMP, up to 30 min after its administration, still represents LCBFs. Our data indicate that, provided the tracer is injected directly into the left ventricle, there is little back diffusion from normal brain to blood under physiological conditions for at least 35 min following the tracer injection and an injection of unlabelled IMP, in a dose larger than that used for blood flow determination, does not displace any labelled IMP previously taken up by the brain, nor does it displace any labelled IMP previously accumulated in the lung that would lead to secondary brain uptake. On the basis of these results, we conclude that sequential autoradiographic determinations of LCBF using IMP labelled with different radionuclides is possible. This is a promising experimental method for the simultaneous investigation of changes in LCBF in several CNS structures.

Amphetamines

The effects of etomidate in the cat middle cerebral artery occlusion model of brain ischaemia. An experimental study.

The effects of etomidate on focal cerebral ischaemia following transorbital occlusion of the cat middle cerebral artery were investigated. Etomidate had no effect on CBF before or after onset of ischaemia by comparison with controls, but caused a greater fall in CBF in cats with high preocclusion or initial ischaemic CBF than in those in which CBF was lower. There were more sustained rises in Kp on SG. The established flow threshold for water accumulation was lost; more gyri with CBF above and fewer gyri with CBF below the flow threshold accumulated water. The relationship between mean occlusion CBF and in vitro GABA uptake was lost; uptakes from MG were lower and from SG and EG higher than expected. In the ischaemic penumbra there was a trend towards reduction in CBF, disruption of ion homeostasis and cerebral oedema formation, whilst in areas of lower flow there was some recovery of GABA uptake and less cerebral oedema following administration of etomidate.

Animals

Protection of respiration of a crude mitochondrial preparation in cerebral ischaemia by control of blood glucose.

There is evidence that systemic hyperglycaemia influences the evolution of cerebral ischaemia adversely, through enhancement of brain lactic acidosis. A potential protective regimen based on induction of mild hypoglycaemia with insulin was therefore studied. Respiratory control in brain mitochondria prepared from the ischaemic hemisphere of rats subjected to unilateral common carotid artery occlusion for one hour was abolished, but was partially preserved in insulin-treated rats (p = 0.01).

Animals

The effects of hyperglycaemia on changes during reperfusion following focal cerebral ischaemia in the cat.

The effects of isosmolar loads of glucose and saline after onset of focal cerebral ischaemia (middle cerebral artery occlusion) were compared in cats. In cats given saline cerebral blood flow (CBF) fell and then rose slightly on the marginal gyrus (infarct penumbra). There was a sustained fall in CBF on the suprasylvian and ectosylvian gyri (infarct core). Reperfusion restored blood flow to preocclusion levels with no overall postischaemic hypoperfusion. Below ischaemic flows of 14 ml/100 g/min brain specific gravity was reduced in a smaller proportion of gyri by contrast with non reperfused cortex, suggesting that in some gyri resolution of cerebral oedema had taken place. GABA uptake was normal in the infarct core, but was reduced within the ischaemic penumbra. In animals given glucose after occlusion, CBF fell on the marginal gyrus during reperfusion. The degree of resolution of cerebral oedema was less than in saline infused cats. GABA uptake showed a pattern of abnormality similar to that seen in saline infused cats, except that uptake values were lower in the infarct core. Pial surface potassium activity remained elevated in the penumbra following reperfusion in glucose infused cats, but returned to normal in saline infused cats. Implications for the management of cerebral ischaemia in man are discussed.

Animals

[Hypotension and diffusion of Rb-86 in the rat brain].

Studies on the permeability of potassium at the blood-brain barrier of rats show that, under normal conditions, the concentration of this ion is kept constant although wide variations in plasma are present. 86Rb has been utilized as an analog of K+. The permeability constant for control animals (arterial blood pressure of 100 +/- 3 mmHg), has been determined in 0.926 +/- 0.02 ml X g-1 X h-1 (brain cortex), and 1.107 +/- 0.12 ml X g-1 X h-1 (cerebellum). The permeability constant for hypotensive animals (arterial blood pressure of 40 +/- 5 mmHg), has been determined in 0.473 +/- 0.03 ml X g-1 X h-1 (brain cortex), and 0.608 +/- 0.06 ml X g-1 X h-1 (cerebellum). During hypotension there is a marked decrease in the permeability constant of 86Rb at the blood-brain barrier of rats.

Animals

The cortical ischaemic penumbra associated with occlusion of the middle cerebral artery in the cat: 1. Topography of changes in blood flow, potassium ion activity, and EEG.

The gyral topography of the ischaemic penumbra associated with middle cerebral artery occlusion was studied in cats; local blood flow (hydrogen clearance, 2-min initial slope analysis), pial surface potassium activity (Kp), and electroencephalogram (EEG) amplitude were recorded on the ectosylvian, suprasylvian, and marginal gyri. Penumbral conditions were defined as a reduction of EEG amplitude in the absence of a major increase in Kp. Whole hemisphere cerebral blood flow prior to occlusion was 35.6 +/- 11.4 (SD) ml 100 g-1 min-1 (n = 25), and fell significantly (p less than 0.001) to 13.0 +/- 4.7 (SD), 14.1 +/- 6.6, and 23.8 +/- 9.3 on ectosylvian, suprasylvian, and marginal gyri, respectively. Pre-occlusion Kp was 3.0 +/- 0.9 mM (n = 53); sustained, steady-state increases in excess of 11.5 mM occurred in 5 of 7 (71%) experiments on ectosylvian gyrus, in 13 of 22 (59%) experiments on suprasylvian gyrus, and in 2 of 24 experiments on marginal gyrus. Transient increases in Kp occurred at occlusion and resolved to baselines significantly higher than control in 5 (23%) experiments in suprasylvian gyrus and in 15 (63%) on marginal gyrus. In 7 experiments on the marginal gyrus (29%), no increase in Kp greater than 1 mM occurred. In contrast, EEG amplitude on this gyrus was reduced by middle cerebral artery occlusion in 25 of 26 experiments, and it is concluded that this gyrus is the principal site of ischaemic penumbra in the model; in 41% of experiments similar conditions were also present on the suprasylvian gyrus.

Animals

The cortical ischaemic penumbra associated with occlusion of the middle cerebral artery in the cat: 2. Studies of histopathology, water content, and in vitro neurotransmitter uptake.

The nature of the ischaemic penumbra, as defined by suppression of electroencephalogram amplitude in the absence of increase in steady state pial surface potassium activity in excess of 13 mM, was examined in the marginal gyrus of cats subjected to middle cerebral artery occlusion. In vitro synaptosomal neurotransmitter uptake, water content (specific gravity), and histopathology at the light and electron microscopic level were studied and the results compared with those obtained at deeper, critical levels of ischaemia (less than 15 ml 100 g-1 min-1). [3H]4-Aminobutyric acid uptake was 104% of control in the marginal gyrus (NS), and 61 and 48% (p less than 0.05) in critical ischaemia. It is concluded that impairment of in vivo synaptosomal uptake is a marker of simultaneous widespread damage to neurones, rather than of a change restricted to the synaptic compartment, although the present findings cannot exclude reversible, substrate-limited impairment of uptake in vivo. Reductions in specific gravity were seen only with critical ischaemia. In 5 of 6 experiments, early or classical ischaemic neuronal cell changes and reactive glia were seen on light microscopy in restricted areas in the marginal gyrus, either in microfoci or scattered more diffusely. Ultrastructural changes were more frequent but were considered to affect only a minority of neurones. Hypotheses for selective electrophysiological suppression in penumbra are discussed.

Animals

Brain abscess.

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Adrenal Cortex Hormones

Kinetics of resolution of transient increases in extracellular potassium activity: relationships to regional blood flow in primate cerebral cortex.

Previous studies have established that in cerebral cortex subjected to progressive reduction in blood flow, two distinct thresholds of flow may be identified below which cellular function is impaired: the cortical evoked response loses amplitude when local flow falls below 18ml/100gm/min, and below 11ml/100gm/min a major increase in extracellular K+ activity (Ke) occurs. However, further evidence suggests that even at higher flows the capacity of the tissue to handle induced ionic changes may be impaired. To investigate this point, we studied the kinetics of resolution of Ke following a transient increase produced by local electrical stimulation, in relation to the local pre-stimulus flow (reduced by acute middle cerebral artery occlusion) in baboons. Flow was measured by the hydrogen clearance method and Ke by ion-exchanger micro-electrodes, in the same cortical regions. In primary induced transients (those increases in Ke elicited by cortical stimulation, and reported previously,) Ke attained a maximum value of 8-10 mM and then decayed towards the 4-mM baseline. The half-time of this decay was significantly increased from normal in the flow range 20-40 ml/100 gm/min, and increased further at lower flows until, below 11ml/100gm/min, Ke clearance was undetectable. Thus, cortical ion homeostasis appeared impaired at flows substantially closer to normal than those thresholds mentioned above, a result discussed in terms of impairment of active Ke clearance mechanisms. Secondary induced transients arose during a primary induced transient, reaching considerably higher peak values (8-30 mM) of Ke (indicating temporary clearance loss) and with slower decay rate than the primary. Spontaneous transients, not associated with any stimulus, were also observed; like secondary transients, they occurred only at flows below 20ml/100gm/min and showed a reduction in clearance rate with progressive ischemia. They resemble spreading depression and their generation is discussed in terms of the ionic and metabolic conditions at their time of origin.

Animals

Synaptosomes prepared from fresh human cerebral cortex; morphology, respiration and release of transmitter amino acids.

Synaptosomes prepared from fresh human cerebral cortex were shown to be morphologically similar to those from other species. On incubation, they took up oxygen at a high and linear rate and accumulated potassium against a concentration gradient. In response to depolarization by raised extracellular K+ or addition of veratrine, they showed increased respiration, lowered tissue potassium, and enhanced release of glutamate, aspartate and GABA. The preparation may be of value for studies of neurological disorders.

Amino Acids