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Biomedical subjects

I R Whittle

Publications and source records attributed to I R Whittle.

At least 19 recordsLinked to original sources
PubMed2006

Unsuccessful intraventricular pentosan polysulphate treatment of variant Creutzfeldt-Jakob disease.

Pentosan polysulphate, delivered by chronic intraventricular infusion, has been proposed as a potential therapy for human prion disease. The first treated patient is still alive several years after treatment started. Here we describe in detail a case of variant Creutzfeldt-Jakob disease in which this treatment was started at a relatively early stage but had no definite clinical benefit. The patient died from disease progression 16 months after diagnosis and 5 months after pentosan polysulphate treatment was commenced.

Adult↗
PubMed2006

Tectal plate cyst in adults.

Tectal plate cysts are very rare. We report two adult patients with benign tectal plate cyst and secondary hydrocephalus. The first patient had an unusual eye movement disorder with bilateral upper eyelid retraction (Collier's sign), limited upgaze, severe upgaze evoked nystagmus and retraction nystagmus. The second patient presented with ataxia and failure of upward gaze. Endoscopic fenestration of the tectal plate cyst and endoscopic third ventriculostomy in both cases result in neurological improvement. To the best of our knowledge, similar lesions at this site have not been reported in adults. The differential diagnosis with arachnoid cysts of the quadrigeminal CSF cistern is discussed.

Adult↗
PubMed2006

An unusual progression of benign thoracic spinal cord teratoma in pregnancy: a hormonally-mediated pathway?

Intradural spinal cord teratoma is a very rare tumour that can be associated with dysraphism. The relationship of this lesion to pregnancy is unknown and its occurrence during pregnancy in the thoracic spine has not been previously reported. We report a 19-year-old pregnant woman with spinal dysraphism, who presented with a new onset thoracic myelopathy. The MRI scan showed an intradural, extramedullary lesion with solid and cystic component in the thoracic spine at the level of T5-T6. A thoracic laminectomy and excision of this lesion was followed by significant improvement of her lower limb function. Histopathology confirmed a benign mature teratoma. The rapid progression of this lesion during pregnancy suggests a hormonal mediated pathway for the tumour growth. Further analysis from the resected specimen confirmed that the tumour was oestrogen and progesterone receptors positive.

Adult↗
PubMed2006

Information processing in patients with intracranial tumours: A preliminary evaluation of the clinical utility of inspection time.

Psychomotor slowing is a common feature in many patients with intracranial tumours. We therefore performed a preliminary study to determine if inspection time, a measure of the efficiency of the brain's information processing, was impaired in patients with intracranial tumours. Inspection time, and some other neuropsychological and functional tests, were compared in 23 people with intracranial tumours and 24 spinal surgery controls prior to surgery. Groups were matched for sex, age and education. Inspection time scores were poorer in the brain tumour group (p < 0.003) and the effect size was moderate (eta2 = 0.197). The brain tumour group also had lower scores on the Boston Aphasia Severity Rating Scale, more anxiety on the Hospital Anxiety Depression Scales, but better Karnovsky Performance scores. Other cognitive and functional tests showed no significant differences between the groups, although group sizes were small. There were no significant changes in inspection time after spinal surgery; however, after intracranial tumour surgery, approximately 30% of patients showed no change, 30% deteriorated and 40% improved. This preliminary study suggests that recording inspection time, in a neuro-oncological setting, may prove informative and practically useful in assessing non-motor processing speed in people with brain tumours.

Brain Neoplasms↗
PubMed2006

Effects of dexamethasone on cerebral perfusion and water diffusion in patients with high-grade glioma.

BACKGROUND AND PURPOSE: The mechanisms by which the glucocorticoid dexamethasone produces its therapeutic action in patients with intracranial tumors still remain unclear. The purpose of this study was to investigate whether dexamethasone affects cerebral perfusion and water molecule diffusion by using quantitative dynamic susceptibility contrast perfusion MR imaging (DSC-MR imaging) and diffusion tensor MR imaging (DT-MR imaging). METHODS: Ten consecutive patients with glioblastoma multiforme underwent DSC-MR imaging and DT-MR imaging before and 48-72 hours after dexamethasone treatment (16 mg/day). Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and water mean diffusivity ( ) were measured for enhancing tumor, nonenhancing peritumoral edematous brain, and normal-appearing contralateral white matter before and after steroid therapy. The percentage change in CBF, CBV, MTT, and for the 3 tissue types was calculated for each patient, a mean value obtained for the population, and the statistical significance determined by using a paired-samples Student t test. RESULTS: After dexamethasone treatment, there was no significant change in tumor CBF, CBV, or MTT. Edematous brain CBV and MTT were also unchanged. There was, however, an increase in edematous brain CBF (11.6%; P = .05). was reduced in both enhancing tumor (-5.8%; P = .001) and edematous brain (-6.0%; P < .001). There was no significant change in CBF, CBV, MTT, or for normal-appearing contralateral white matter after treatment. CONCLUSION: These data suggest that dexamethasone does not significantly affect tumor blood flow but may, by reducing peritumoral water content and local tissue pressure, subtly increase perfusion in the edematous brain.

Adult↗
PubMed2005

11beta-Hydroxysteroid dehydrogenase type 2 protects the neonatal cerebellum from deleterious effects of glucocorticoids.

11beta-Hydroxysteroid dehydrogenase type 2 is a glucocorticoid metabolizing enzyme that catalyzes rapid inactivation of corticosterone and cortisol to inert 11-keto derivatives. As 11beta-hydroxysteroid dehydrogenase type 2 is highly expressed in the developing brain, but not in the adult CNS, we hypothesized that it may represent a protective barrier to the deleterious actions of corticosteroids on proliferating cells. To test this hypothesis we have investigated the development and growth of the cerebellum in neonatal C57BL/6 mice and mice lacking 11beta-hydroxysteroid dehydrogenase type 2 (-/-). 11beta-Hydroxysteroid dehydrogenase type 2-/- mice had consistently lower body weight throughout the neonatal period, coupled with a smaller brain size although this was normalized when corrected for body weight. The cerebellar size was smaller in 11beta-hydroxysteroid dehydrogenase type 2-/- mice, due to decreases in size of both the molecular and internal granule layers. When exogenous corticosterone was administered to the pups between postnatal days 4 and 13, 11beta-hydroxysteroid dehydrogenase type 2(-/-) mice were more sensitive, showing further inhibition of cerebellar growth while the wildtype mice were not affected. Upon withdrawal of exogenous steroid, there was a rebound growth spurt so that at day 21 postnatally, the cerebellar size in 11beta-hydroxysteroid dehydrogenase type 2-/- mice was similar to untreated mice of the same genotype. Furthermore, 11beta-hydroxysteroid dehydrogenase type 2-/- mice had a delay in the attainment of neurodevelopmental landmarks such as negative geotaxis and eye opening. We therefore suggest that 11beta-hydroxysteroid dehydrogenase type 2 acts as to protect the developing nervous system from the deleterious consequences of glucocorticoid overexposure.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2005

Assessment of different data representations and averaging methods on the Spiegelberg compliance device.

The Spiegelberg Compliance Device (Spiegelberg KG, Hamburg, Germany) has been available for the automated measurement and calculation of minute by minute intracranial compliance. Widespread practical use has been somewhat limited by the instability of values: especially at low intracranial pressures. We looked at two aspects of a methodology in an attempt to increase the value of the Spiegelberg device in the clinical setting. Firstly, we discussed the difference in representing measured values as elastance (dp/dv) instead of compliance (dv/dp); and secondly we proposed the use of an averaging algorithm called the Exponentially Weighted Moving Average (ewma), which could be applied as a flexible method to follow trends and rapid changes in the elastance (or compliance). Clinical data from sixteen patients were gathered and statistical analysis was focused on three particular aspects, the coefficient of variation which indicates the variability of data values, the correlation between the elastance (or compliance) time series and the underlying ICP signal and the percentage of outliers greater than 2.5 standard deviations from the mean. Our results showed that expressing elastance (dp/dv) instead of compliance (dv/dp) yielded fewer outliers and had a better correlation to ICP, and the ewma method had a better correlation to ICP than the Spiegelberg method.

Adult↗
PubMed2005

Patient perceptions of "awake" brain tumour surgery.

BACKGROUND: Awake brain tumour surgery allows intraoperative patient assessment and is done to optimise safe tumour removal. It is an established technique but little is known about patient perceptions of the procedure. METHOD: Fifteen adult patients filled out a dedicated questionnaire to assess 10 aspects of patient perceptions of the procedure. FINDINGS: All patients, who were awake for a median of 45 minutes (range 10-105), stated they were adequately prepared for the operation. Most recollected various aspects of the procedure, although 3 patients (20%) had little memory of actually being awake during the surgery despite being cooperative. A minority reported more than minor discomfort (20%), fear (15%) or anxiety (29%), and most felt they coped with the cortical stimulations and functional testing well. Sources of discomfort and pain were the cranial pin holding device, operative position, inadequate infiltration of the cranial wound with local anesthetic, a full bladder causing a desire to micturate and a hard and uncomfortable operating table. CONCLUSIONS: These results, are very similar to a previous American report using a different anesthetic technique, in that most patients tolerate awake craniotomy remarkably well if the procedure is explained to them and some simple precautions are taken. Additionally between 8%-37% of patients (95% Confidence Interval, summing data from the two studies, n = 35) will have no recollection of being awake. Ways of minimising discomfort and problems of anxiety in this patient cohort are discussed.

Adaptation, Psychological↗
PubMed2005

Real-time functional magnetic resonance imaging (rt-fMRI) in patients with brain tumours: preliminary findings using motor and language paradigms.

Functional MRI (fMRI) shows areas of the brain that are active during a task, but the standard approach (offline analysis after the imaging has finished) precludes tailoring of the imaging to the individual patient, e.g. for assessing normal function around an individual lesion. The aims of the study were to explore the technical feasibility of acquiring functional images in real-time (rt-fMRI), develop the necessary software interfaces and protocols for image acquisition, and to compare images of functional activation acquired in real-time with the standard offline statistical parametric method in patients with solitary brain tumours. Patients with a solitary supratentorial lesion were studied. The rt-fMRI paradigms were sequential finger opposition, ankle movement and language function (correct recognition of grammatically violated sentences). Datasets were analysed using AFNI software (National Institute of Mental Health, Bethesda, Maryland, USA) for the real-time analysis and SPM99 (Functional Imaging Laboratory, University College, London, UK) for the offline analysis. From 11 patients, useful data were obtained in nine. The finger tapping task produced most consistent activation between real-time and offline analysis with good anatomic localization to the primary motor cortex contralateral to the tapping finger. Ankle movement produced weaker activation and correlation with real-time analysis. For the language task the offline analysis provided reproducible activation patterns, but the real-time method showed no activation at the chosen threshold of p = 0.001. Tumourous areas of brain did not show any activation with either method of analysis during any task. rt-fMRI is feasible and could be a valuable functional evaluation tool in the planning of surgery for tumours in motor regions of the brain. Further paradigm development is required for evaluation of language, and possibly other more complex executive functions.

Adult↗
PubMed2005

The accuracy of meningioma grading: a 10-year retrospective audit.

Although descriptive classifications of meningioma subtypes are well established, there has been inconsistency in the categorization of meningiomas into benign, atypical and anaplastic groups. The aim of this study was to reassess the incidence of atypical (grade II) meningiomas over a 10-year period by applying the World Health Organization (WHO) 2000 classification system. A secondary aim was to determine if grade II and III tumours were becoming more common. Sections of 314 meningiomas resected between 1994 and 2003 were retrieved from the archives of the Western General Hospital's neuropathology unit in Edinburgh. They were reassessed and graded by using the WHO 2000 classification system. The reviewers were blind to the original classification and grading. There was a gradual increase in the numbers of meningiomas being resected annually over the 10-year period. On reclassification, 78% of the meningiomas were classified as grade I, 20.4% as grade II and 1.6% as grade III. With regard to grade II meningiomas classified by using the WHO 2000 classification system, 38.1% had originally been classified as grade I prior to 2000, whereas 13.6% had originally been classified as grade I after 2000. In most cases, reclassification was due to formal counts of mitotic figures. Atypical meningiomas are diagnosed more frequently under the current WHO classification system than they were under the previous classification systems. Although the current WHO (2000) classification is more prescriptive than its predecessors, interobserver variability is likely to remain because of the subjective nature of some of the criteria.

Adolescent↗
PubMed2005

Discovery of a perinecrotic 60 kDa MDM2 isoform within glioma spheroids and glioblastoma biopsy material.

Necrosis in glioblastoma is often associated with high levels of Fas (APO-1), HIF-1alpha and PARP expression. The presence of such molecules suggests a regulative element to cell death within this tissue, which may involve p53. We aimed to establish whether p53 and its downstream targets Bax, MDM2 and p21 play a role in perinecrotic cell death in glioblastoma. Following sequencing of the p53 gene in U87 and U373 glioma cell lines, p53 was found to be reactive in the p53 wild-type line U87 in response to hypoxia but not in the p53 mutant line, U373. Although no increase in perinecrotic p53 expression was detected in spheroid cultures derived from these lines, a 60 kDa MDM2 isoform lacking a C-terminal domain showed perinecrotic localization, irrespective of p53 status. Similar findings were observed surrounding regions of necrosis in 80% of glioblastoma biopsies examined. Increasing levels of wild-type p53 did not affect cell death in U87 spheroid cultures but killed all U373 cells 3 days post transfection. Dominant negative p53 did not affect cell death in U373 and U87 spheroid cultures. Although p53 accumulation appeared not to be important for the onset of cell death both in spheroid and biopsy cases, high levels of perinecrotic 60 kDa MDM2 may have implications for glioma cell death susceptibility in both p53 mutant and wild-type tumour cell populations.

Apoptosis↗
PubMed2004

Intracellular oxidation by human glioma cell populations: effect of arachidonic acid.

Arachidonic acid (AA) and Gamma linolenic acid have been shown to limit glioma cell growth, stimulate apoptosis and lipid peroxidation. However, brain tumours are characterised by cellular heterogeneity and responding cell populations have not been identified. Brain tumour samples from patients were disaggregated. In cell preparations from 7 gliomas, reactive oxygen species (ROS), morphology and plasma membrane integrity were monitored +/-18-36 microM AA for 15-120 min using flow cytometry. Basal oxidative activity related to cell size/morphology, small granular cells showed lower activity. AA stimulation of ROS formation depended on cell size/morphology. Large, less granular cells showed greater AA stimulation. In 17 gliomas, GFAP immunofluorescence was demonstrated in larger cell populations. The large GFAP positive cell population with low side scatter was the highest responding cell population, suggesting selective tumour cell sensitivity to AA induced ROS formation. ROS may have a role in AA induced cell death and anti-tumour activity of AA in glioma.

Antineoplastic Agents↗
PubMed2004

Effects of dexamethasone on peritumoural oedematous brain: a DT-MRI study.

OBJECTIVES: Glucocorticoids (dexamethasone) are thought to reduce peritumoural brain oedema by decreasing the permeability of neoplastic capillaries and/or enhancing the clearance of extracellular water. Diffusion tensor magnetic resonance imaging (DT-MRI) was used to measure the water diffusion parameters of oedematous and normal brain in a group of patients with intracranial tumours before and after steroid treatment. METHODS: Fifteen patients with intracranial tumours (seven with high-grade glioma, four with metastatic carcinoma and four with meningioma) were examined before and 48-72 h after dexamethasone treatment (16 mg/day). The mean diffusivity ( ) and fractional anisotropy (FA) were measured for oedematous brain and apparently normal contralateral white matter before and after steroid therapy. RESULTS: In all three patient groups there was a significant decrease in of oedematous brain after steroid treatment (p<0.01). There was no significant change in FA of oedematous brain after treatment in any of the three groups. There was also no significant change in either or FA of apparently normal contralateral white matter after treatment. CONCLUSION: These data indicate that dexamethasone produces a localised reduction in the magnitude of extracellular water molecule mobility, and hence water content, in peritumoural oedematous brain. Furthermore, the magnitude of these changes is similar for both intra- and extra-axial tumours.

Adult↗