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Biomedical subjects

R Kett-White

Publications and source records attributed to R Kett-White.

13 recordsLinked to original sources

Extracellular amino acid changes in patients during reversible cerebral ischaemia.

This study investigated the changes in extracellular chemistry during reversible human cerebral ischaemia. Delayed analysis was performed on samples taken from a subgroup of patients during aneurysm surgery previously reported. Frozen microdialysis samples from 14 patients who had all undergone temporary clipping of the ipsilateral internal carotid artery (ICA) were analysed for another 15 amino acids with HPLC and for glycerol with CMA-600. Changes were characterised according to whether cerebral tissue oxygen pressure (PBO2) decreases were brief or prolonged. Brief ICA clipping (maximum duration of 16 minutes) in 11 patients was not associated with changes in amino acids or glycerol. Cerebral ischaemia, defined by a PBO2 decrease below 1.1 kPa for at least 30 minutes during ICA occlusion, occurred in 3 patients. None of whom developed an infarct in the monitored region. This prolonged reversible ischaemia was associated with transient delayed increases in gamma-amino butyric acid (GABA) as well as glutamate and glycerol, each by two-to-three folds. This study demonstrates detectable transient increases in human extracellular glutamate, GABA and glycerol during identified periods of reversible cerebral ischaemia, maximal 30-60 minutes after onset of ischaemia, but not in other amino acids detected by HPLC.

Adult↗

Multi-modal monitoring of acute brain injury.

OBJECTIVE: To review the scientific basis for and utility of the traditional cerebral monitors used currently in neurointensive care, together with research techniques that are soon likely to become used in managing severe head injury and subarachnoid haemorrhage. DESIGN AND CONTENT: Firstly, the pathophysiology of acute brain injury including cerebral haemodynamics, oxygen and metabolism and the role of secondary insults are discussed. Secondly, the importance of assessment of cerebrovascular autoregulation and reactivity is reviewed together with methods for its continuous non-invasive measurement using transcranial Doppler and intracranial pressure/arterial pressure recordings. Thirdly, the respective roles of jugular venous oxygen and brain tissue oxygen monitoring are analysed. Fourthly, the use of cerebral microdialysis is described, together with an overview of its utility. CONCLUSION: Cerebral multimodal monitoring can be helpful for the optimal management of acute brain injury and essential for future exploratory trials of neuroprotective drugs.

Acute Disease↗

Effects of variation in cerebral haemodynamics during aneurysm surgery on brain tissue oxygen and metabolism.

OBJECTIVES: This study explores the sensitivities of multiparameter tissue gas sensors and microdialysis to variations in blood pressure, CSF drainage and to well-defined periods of ischaemia accompanying aneurysm surgery, and their predictive value for infarction. METHODS: A Neurotrend sensor [brain tissue partial pressure of oxygen (PBO2), carbon dioxide (PBCO2), brain pH (pHB) and temperature] and microdialysis catheter were inserted into the appropriate vascular territory prior to craniotomy. RESULTS: Baseline data showed a clear correlation between PBO2 and mean arterial pressure (MAP) below a threshold of 80 mmHg. PBO2 improved with CSF drainage in 20 out of 28 (Wilcoxon: P < 0.05) cases where data was available. In 26 patients the effects of temporary vascular clipping (TC) (mean duration 16 minutes) were assessed. 2 patients subsequently declared infarction in the region of the probes. PBO2 fell from a mean 3.2 (95% CI 2.4-4.1) kPa to a minimum of 1.5 (95% CI 1.0-2.0) kPa in the non-infarct group. There was a lower baseline PBO2 (mean 0.8 kPa) in the patients who infarcted. PBCO2 mirrored PBO2 changes, whereas pHB did not change significantly in either group. Microdialysis changes associated with decreased PBO2 included a delayed increase in lactate, a raised lactate/pyruvate ratio and more rarely an increased glutamate. These changes were seen in 11 patients but were not predictive of infarction. CONCLUSION: Hypotension during aneurysm surgery is associated with a low PBO2. Multiparameter sensors can be sensitive to acute ischaemia. Microdialysis shows potential in the detection of metabolic changes during tissue hypoxia.

Adult↗

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↗

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↗

Malignant spinal neurofibrosarcoma.

STUDY DESIGN: A report of a case of metastatic spinal neurofibrosarcoma. OBJECTIVE: To document metastatic neurofibrosarcoma as a cause of spinal cord compression and to review the literature. SUMMARY OF BACKGROUND DATA: Three previously reported cases of metastatic neurofibrosarcoma of the spine were reviewed. METHODS: The patient's clinical record and radiologic investigations as well as the result of a search of the English literature are reported. Magnetic resonance images, computed tomographic scans, and histology photomicrographs are displayed. RESULTS: Paraparesis developed in this patient, due to a posterior extradural thoracic spinal cord compression by a neurofibrosarcoma believed to be metastatic from a neurofibrosarcoma of the femoral nerve. CONCLUSIONS: Malignant spinal metastasis remains a rare complication of neurofibromatosis, with a very poor prognosis.

Fatal Outcome↗

Clinical cerebral microdialysis: a methodological study.

OBJECT: Clinical microdialysis enables monitoring of the cerebral extracellular chemistry of neurosurgical patients. Introduction of the technique into different hospitals' neurosurgical units has resulted in variations in the method of application. There are several variables to be considered, including length of the catheter membrane, type of perfusion fluid, flow rate of perfusion fluid, and on-line compared with delayed analysis of samples. The objects of this study were as follows: 1) to determine the effects of varying catheter characteristics on substance concentration; 2) to determine the relative recovery and true extracellular concentration by varying the flow rate and extrapolating to zero flow; and 3) to compare substance concentration obtained using a bedside enzyme analyzer with that of off-line high-performance liquid chromatography (HPLC). METHODS: A specially designed bolt was used to conduct two adjacent microdialysis catheters into the frontal cortex of patients with head injury or poor-grade subarachnoid hemorrhage who were receiving ventilation. One reference catheter (10-mm membrane, perfused with Ringer's solution at 0.3 microl/minute) was constant for all studies. The other catheter was varied in terms of membrane length (10 mm or 30 mm), perfusion fluid (Ringer's solution or normal saline), and flow rate (0.1-1.5 microl/minute). The effect of freezing the samples on substance concentration was established by on-line analysis and then repeated analysis after storage at -70 degrees C for 3 months. Samples assayed with the bedside enzyme analyzer were reassessed using HPLC for the determination of glutamate concentrations. CONCLUSIONS: Two adjacent microdialysis catheters that were identical in membrane length, perfusion fluid, and flow rate showed equivalent results. Variations in perfusion fluid and freezing and thawing of samples did not result in differences in substance concentration. Catheter length had a significant impact on substance recovery. Variations in flow rate enabled the relative recovery to be calculated using a modification of the extrapolation-to-zero-flow method. The recovery was approximately 70% at 0.3 microl/minute and 30% at 1 microl/minute (10-mm membrane) for all analytes. Glutamate results obtained with the enzyme analyzer showed good correlation with those from HPLC.

Adult↗

Spontaneous intralesional haemorrhage in dysembryoplastic neuroepithelial tumours: a series of five cases.

Five patients with dysembryoplastic neuroepithelial tumour (DNT) showing extensive secondary haemorrhage, a finding not previously associated with these neoplasms, are described. The clinical presentations, neuroimaging findings, and histopathological features of these patients are reviewed. One patient, a previously asymptomatic 12 year old girl, presented with an acute intracerebral haemorrhage into a DNT. A further four young adults with histories of intractable partial and generalised seizures dating from childhood showed significant chronic haemorrhages within DNT, the MRI appearances in one patient giving a false impression of a cavernoma. Histopathology disclosed vascular abnormalities within these tumours which, together with other factors discussed, may have predisposed these tumours to haemorrhage.

Brain Neoplasms↗

Sprouting of peripherally regenerating primary sensory neurones in the adult central nervous system.

We have studied the ability of primary afferent neurones to proliferate within the grey matter of the dorsal horn following the degeneration of other, nearby, afferent fibres. The peripheral branches of primary afferents have the capacity to regenerate successfully over long distances, and we have examined the possibility that when they are so doing, the neurones' status changes to facilitate greatly the sprouting of afferent fibres within the dorsal horn. "Spared root" preparations (rhizotomies of L3, L4, L6, S1, and the caudal half of L5, sparing the rostral half of the L5 dorsal root) were made in adult rats. In some animals (acute preparations) the distribution of the central terminals of the spared root was assessed by labelling the sciatic nerve with WGA-HRP at the time of the rhizotomies. In other animals (chronic preparations), symmetrical bilateral spared roots were made and the sciatic nerve on one side was concomitantly crushed to trigger regrowth of the peripheral branches of these axons. Eight to 10 weeks later the sciatic nerves on both sides were labelled with HRP-WGA. In the acute preparations the reaction product was found in a limited rostrocaudal and mediolateral region of the dorsal horn. In lamina II (the lamina of densest labelling) the labelled terminals occupied an average of 1.17 +/- 0.21 mm2. In chronic preparations, the area of labelled terminals on the side of the uncrushed sciatic nerve was 1.34 +/- 0.28 mm2 (not significantly different from acute animals). However, the labelled area on the side of the crushed sciatic nerve was significantly greater, averaging 2.17 +/- 0.14 mm2.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗