36 results on '"MacArthur DC"'
Search Results
2. Minor Head Injury
- Author
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Macarthur Dc and Price Rf
- Subjects
Injury control ,Minor Head Injury ,business.industry ,Accident prevention ,Human factors and ergonomics ,Poison control ,Ultrasonography, Doppler ,Prognosis ,medicine.disease ,Severity of Illness Index ,Suicide prevention ,Occupational safety and health ,Predictive Value of Tests ,Cerebrovascular Circulation ,Injury prevention ,Craniocerebral Trauma ,Humans ,Medicine ,Medical emergency ,business ,Blood Flow Velocity - Published
- 1997
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3. Neurological deterioration years after closure of myelomeningocoele – `the second lesion'
- Author
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Macarthur, DC, primary, Punt, JA, additional, Spencer, M, additional, Douglas, DL, additional, White, BD, additional, and Holland, IM, additional
- Published
- 2001
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4. Comparison of Echo Planar and Turbo Spin Echo Diffusion-Weighted Imaging in Intraoperative MRI.
- Author
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Thorpe JC, Thust SC, Gillon CHM, Rowe S, Swain CE, MacArthur DC, Howarth SP, Avula S, Morgan PS, and Dineen RA
- Abstract
Background: Diffusion-weighted imaging (DWI) is routinely used in brain tumor surgery guided by intraoperative MRI (IoMRI). However, conventional echo planar imaging DWI (EPI-DWI) is susceptible to distortion and artifacts that affect image quality. Turbo spin echo DWI (TSE-DWI) is an alternative technique with minimal spatial distortions that has the potential to be the radiologically preferred sequence., Purpose: To compare via single- and multisequence assessment EPI-DWI and TSE-DWI in the IoMRI setting to determine whether there is a radiological preference for either sequence., Study Type: Retrospective., Population: Thirty-four patients (22 female) aged 2-61 years (24 under 18 years) undergoing IoMRI during surgical resection of intracranial tumors., Field Strength/sequence: 3-T, EPI-DWI, and TSE-DWI., Assessment: Patients were scanned with EPI- and TSE-DWI as part of the standard IoMRI scanning protocol. A single-sequence assessment of spatial distortion and image artifact was performed by three neuroradiologists blinded to the sequence type. Images were scored regarding distortion and artifacts, around and remote to the resection cavity. A multisequence radiological assessment was performed by three neuroradiologists in full radiological context including all other IoMRI sequences from each case. The DWI images were directly compared with scorings of the radiologists on which they preferred with respect to anatomy, abnormality, artifact, and overall preference., Statistical Tests: Wilcoxon signed-rank tests for single-sequence assessment, weighted kappa for single and multisequence assessment. A P-value <0.001 was considered statistically significant., Results: For the blinded single-sequence assessment, the TSE-DWI sequence was scored equal to or superior to the EPI-DWI sequence for distortion and artifacts, around and remote to the resection cavity for every case. In the multisequence assessment, all radiologists independently expressed a preference for TSE-DWI over EPI-DWI sequences on viewing brain anatomy, abnormalities, and artifacts., Data Conclusion: The TSE-DWI sequences may be favored over EPI-DWI for IoMRI in patients with intracranial tumors., Level of Evidence: 2 TECHNICAL EFFICACY: Stage 5., (© 2024 The Author(s). Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)
- Published
- 2024
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5. A Reappraisal of the Pathophysiology of Cushing Ulcer: A Narrative Review.
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Kumaria A, Kirkman MA, Scott RA, Dow GR, Leggate AJ, Macarthur DC, Ingale HA, Smith SJ, and Basu S
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- Humans, Vagus Nerve physiopathology, Intracranial Hypertension physiopathology, Intracranial Hypertension etiology, Gastrointestinal Microbiome physiology, Brain Injuries physiopathology, Gastric Acid metabolism, Peptic Ulcer physiopathology
- Abstract
In 1932, Harvey Cushing described peptic ulceration secondary to raised intracranial pressure and attributed this to vagal overactivity, causing excess gastric acid secretion. Cushing ulcer remains a cause of morbidity in patients, albeit one that is preventable. This narrative review evaluates the evidence pertaining to the pathophysiology of neurogenic peptic ulceration. Review of the literature suggests that the pathophysiology of Cushing ulcer may extend beyond vagal mechanisms for several reasons: (1) clinical and experimental studies have shown only a modest increase in gastric acid secretion in head-injured patients; (2) increased vagal tone is found in only a minority of cases of intracranial hypertension, most of which are related to catastrophic, nonsurvivable brain injury; (3) direct stimulation of the vagus nerve does not cause peptic ulceration, and; (4) Cushing ulcer can occur after acute ischemic stroke, but only a minority of strokes are associated with raised intracranial pressure and/or increased vagal tone. The 2005 Nobel Prize in Medicine honored the discovery that bacteria play key roles in the pathogenesis of peptic ulcer disease. Brain injury results in widespread changes in the gut microbiome in addition to gastrointestinal inflammation, including systemic upregulation of proinflammatory cytokines. Alternations in the gut microbiome in patients with severe traumatic brain injury include colonization with commensal flora associated with peptic ulceration. The brain-gut-microbiome axis integrates the central nervous system, the enteric nervous system, and the immune system. Following the review of the literature, we propose a novel hypothesis that neurogenic peptic ulcer may be associated with alterations in the gut microbiome, resulting in gastrointestinal inflammation leading to ulceration., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2024
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6. A common tumour in a rare location: a single centre case series of cerebellar glioblastoma.
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Kumaria A, Leggate AJ, Dow GR, Ingale HA, Robertson IJA, Byrne PO, Basu S, Macarthur DC, and Smith SJ
- Abstract
Although glioblastoma is the commonest primary brain tumour in adults, its location in the cerebellum is extremely rare. We present thirteen cases (3 female, 10 male; median age at presentation 56 [age range 21-77]) of surgically managed, histologically confirmed, primary cerebellar glioblastoma (cGB) over a 17 year period (2005-2022). Pre-operative radiological diagnosis was challenging given cGB rarity, although MRI demonstrated ring enhancement in all cases. Surgical management included posterior fossa craniectomy and debulking in 11 cases and burr hole biopsy in two. CSF diversion was necessary in four cases. No evidence of IDH or ATRX gene mutations was found when tested. Survival ranged from 1 to 22 months after diagnosis (mean 10.9 months). We also seek to understand why glioblastoma is rare in this location and discuss potential reasons for this. We hypothesise that increasing anatomical distance from germinal regions and decreased local endogenous neural stem cell activity (which has been associated with glioblastoma) may explain why glioblastoma is rare in the cerebellum. We hereby seek to add to the limited literature on cGB as this is the largest UK cGB series to date.
- Published
- 2024
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7. Beating a skullduggerous infantile hemispheric high-grade glioma.
- Author
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Kumaria A, Kirkman MA, Howarth SP, and Macarthur DC
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- Male, Humans, Infant, Glioma diagnostic imaging, Glioma surgery, Brain Neoplasms diagnostic imaging, Brain Neoplasms surgery
- Abstract
A case of infantile hemispheric high grade glioma in a five-month-old boy is presented. Striking images of a 'beaten copper pot' skull were concerning at first, but with a successful surgical and oncological plan he is well three years later, displaying only minor signs of developmental delay.
- Published
- 2024
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8. Periventricular lucency in hydrocephalus: a glymphatic viewpoint.
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Kumaria A, Macarthur DC, and Kirkman MA
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- Humans, Tomography, X-Ray Computed, Hydrocephalus diagnostic imaging
- Published
- 2023
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9. Meta-Analysis of Apparent Diffusion Coefficient in Pediatric Medulloblastoma, Ependymoma, and Pilocytic Astrocytoma.
- Author
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Dury RJ, Lourdusamy A, Macarthur DC, Peet AC, Auer DP, Grundy RG, and Dineen RA
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- Child, Diagnosis, Differential, Diffusion Magnetic Resonance Imaging methods, Humans, Retrospective Studies, Astrocytoma diagnostic imaging, Cerebellar Neoplasms diagnostic imaging, Cerebellar Neoplasms pathology, Ependymoma diagnostic imaging, Ependymoma pathology, Infratentorial Neoplasms diagnostic imaging, Infratentorial Neoplasms pathology, Medulloblastoma diagnostic imaging
- Abstract
Background: Medulloblastoma, ependymoma, and pilocytic astrocytoma are common pediatric posterior fossa tumors. These tumors show overlapping characteristics on conventional MRI scans, making diagnosis difficult., Purpose: To investigate whether apparent diffusion coefficient (ADC) values differ between tumor types and to identify optimum cut-off values to accurately classify the tumors using different performance metrics., Study Type: Systematic review and meta-analysis., Subjects: Seven studies reporting ADC in pediatric posterior fossa tumors (115 medulloblastoma, 68 ependymoma, and 86 pilocytic astrocytoma) were included following PubMed and ScienceDirect searches., Sequence and Field Strength: Diffusion weighted imaging (DWI) was performed on 1.5 and 3 T across multiple institution and vendors., Assessment: The combined mean and standard deviation of ADC were calculated for each tumor type using a random-effects model, and the effect size was calculated using Hedge's g., Statistical Tests: Sensitivity/specificity, weighted classification accuracy, balanced classification accuracy. A P value < 0.05 was considered statistically significant, and a Hedge's g value of >1.2 was considered to represent a large difference., Results: The mean (± standard deviation) ADCs of medulloblastoma, ependymoma, and pilocytic astrocytoma were 0.76 ± 0.16, 1.10 ± 0.10, and 1.49 ± 0.16 mm
2 /sec × 10-3 . To maximize sensitivity and specificity using the mean ADC, the cut-off was found to be 0.96 mm2 /sec × 10-3 for medulloblastoma and ependymoma and 1.26 mm2 /sec × 10-3 for ependymoma and pilocytic astrocytoma. The meta-analysis showed significantly different ADC distributions for the three posterior fossa tumors. The cut-off values changed markedly (up to 7%) based on the performance metric used and the prevalence of the tumor types., Data Conclusion: There were significant differences in ADC between tumor types. However, it should be noted that only summary statistics from each study were analyzed and there were differences in how regions of interest were defined between studies., Evidence Level: 1 TECHNICAL EFFICACY: Stage 3., (© 2021 International Society for Magnetic Resonance in Medicine.)- Published
- 2022
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10. Psychrobacter piechaudii shunt infection: first report of human infection.
- Author
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Kumaria A, Crusz SA, Lister M, Kirkman MA, and Macarthur DC
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- Cerebrospinal Fluid Shunts, Female, Humans, Infant, Ventriculoperitoneal Shunt adverse effects, Hydrocephalus diagnostic imaging, Hydrocephalus surgery, Psychrobacter
- Abstract
Psychrobacter piechaudii is a recently described species of Gram-negative bacteria in the Moraxellaceae family. No cases of human infection due to this species have been described before. We report the case of an ex-premature infant girl with hydrocephalus secondary to intraventricular haemorrhage who underwent multiple cerebrospinal fluid (CSF) shunt operations. She ultimately developed Psychrobacter piechaudii meningitis, presenting as ventriculoperitoneal shunt dysfunction and wound leak, which necessitated removal of the shunt, a period of external ventricular drainage and antibiotics. We found this organism to be sensitive to intravenous ceftazidime (50 mg/kg) and ciprofloxacin, and a 7-10 day treatment course prior to shunt re-insertion (and 3 week total course) was sufficient. The patient is well post-operatively. To the best of our knowledge, this is the first reported case of Psychrobacter piechaudii infection in a human., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2022
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11. Glioblastoma multiforme metastatic to lung in the absence of intracranial recurrence: case report.
- Author
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Kumaria A, Teale A, Kulkarni GV, Ingale HA, Macarthur DC, and Robertson IJA
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- Aged, Craniotomy, Humans, Lung pathology, Magnetic Resonance Imaging, Male, Brain Neoplasms diagnostic imaging, Brain Neoplasms surgery, Glioblastoma diagnostic imaging, Glioblastoma surgery
- Abstract
We present the case of a 65 year old gentleman who underwent craniotomy and debulking of a left temporal glioblastoma multiforme (GBM). Post-operatively he received chemotherapy and radiotherapy with good response demonstrated on interval MRI scans. At 17 months post-diagnosis and in the absence of clinical or radiological recurrence, he presented with respiratory distress. He was found to have an exudative right-sided pleural effusion, nodular pleural thickening, a hilar mass and associated lymphadenopathy. Percutaneous pleural biopsy revealed metastatic GBM. Systemic GBM metastasis despite good response to oncological treatments and in the absence of intracranial recurrence is exceedingly rare. We review the literature concerning extra-neuraxial GBM metastasis and speculate why this phenomenon is extremely rare.
- Published
- 2022
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12. An explanation for Terson syndrome at last: the glymphatic reflux theory.
- Author
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Kumaria A, Gruener AM, Dow GR, Smith SJ, Macarthur DC, and Ingale HA
- Subjects
- Humans, Intracranial Pressure, Optic Nerve diagnostic imaging, Vitreous Hemorrhage etiology, Intracranial Hypertension etiology, Subarachnoid Hemorrhage complications
- Abstract
Terson Syndrome (TS) describes the presence of intraocular hemorrhage in patients with intracranial hemorrhage, typically subarachnoid hemorrhage. Despite TS being a well-defined and frequently occurring phenomenon, its pathophysiology remains controversial. This review will present the current understanding of TS, with view to describing a contemporary and more plausible pathomechanism of TS, given recent advances in ophthalmic science and neurobiology. Previously proposed theories include a sudden rise in intracranial pressure (ICP) transmitted to the optic nerve sheath leading to rupture of retinal vessels; or intracranial blood extending to the orbit via the optic nerve sheath. The origin of blood in TS is uncertain, but retinal vessels appear to be an unlikely source. In addition, an anatomical pathway for blood to enter the eye from the intracranial space remains poorly defined. An ocular glymphatic system has recently been described, drainage of which from the globe into intracranial glymphatics is reliant on the pressure gradient between intraocular pressure and intracranial pressure. The glymphatic pathway is the only extravascular anatomical conduit between the subarachnoid space and the retina. We propose that subarachnoid blood in skull base cisterns near the optic nerve is the substrate of blood in TS. Raised ICP causes it to be refluxed through glymphatic channels into the globe, resulting in intraocular hemorrhage. We herewith present glymphatic reflux as an alternative theory to explain the phenomenon of Terson Syndrome., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2022
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13. Successful treatment of giant cavernous carotid artery aneurysm in a child using a flow diverter stent.
- Author
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Kumaria A, McConachie NS, and Macarthur DC
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- Carotid Arteries, Cerebral Angiography, Child, Humans, Stents, Treatment Outcome, Carotid Artery Diseases diagnostic imaging, Carotid Artery Diseases surgery, Endovascular Procedures, Intracranial Aneurysm diagnostic imaging, Intracranial Aneurysm surgery
- Abstract
Giant intracranial aneurysms are extremely rare in children. We present such a case, describe angiographic appearances and successful treatment using a flow diverter stent.
- Published
- 2021
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14. Spontaneous regression of a large skull base meningioma: case report.
- Author
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Kumaria A, Ingale HA, and Macarthur DC
- Subjects
- Female, Humans, Middle Aged, Skull Base, Meningeal Neoplasms, Meningioma, Skull Base Neoplasms
- Abstract
We present the case of a 58 year old lady with a large middle cranial fossa meningioma (5 cm × 4 cm in maximal dimensions) which has considerably regressed without any treatment during seven years of follow up. While the tumour had remained radiologically static for the first three years, scans from year five post-diagnosis onwards have shown shrinkage of the meningioma from a calculated volume of 36 cm
3 to 11.2 cm3 . There has been no intratumoral haemorrhage or infarction and no medication or exogenous hormonal effect that could account for this effect. We reviewed the literature and report that this is only the second ever case of spontaneous regression of meningioma.- Published
- 2020
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15. Recurrent Bell's palsy following ventriculoperitoneal shunt insertion: an unusual case to face.
- Author
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Kumaria A, Hammett TC, Sitaraman M, D'Aquino DA, and Macarthur DC
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- Adolescent, Bell Palsy drug therapy, Bell Palsy physiopathology, Brain Stem Neoplasms complications, Child, Equipment Failure, Glioma complications, Humans, Male, Postoperative Complications drug therapy, Postoperative Complications physiopathology, Prednisolone therapeutic use, Recurrence, Reoperation, Steroids, Bell Palsy etiology, Brain Stem Neoplasms surgery, Glioma surgery, Hydrocephalus surgery, Postoperative Complications etiology, Tectum Mesencephali surgery, Ventriculoperitoneal Shunt adverse effects
- Abstract
We present the case of a 15 year old boy who developed transient lower motor neuron facial weakness on two separate occasions shortly after ventriculoperitoneal shunt insertion. Both episodes, each of which occurred on the ipsilateral side to shunt insertion, were transient, self-limiting and were managed medically with a course of oral steroids. We believe this is the first reported case of Bell's palsy after this type of surgery in a child. Potential pathophysiological mechanisms are discussed.
- Published
- 2018
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16. Development of a pre-operative scoring system for predicting risk of post-operative paediatric cerebellar mutism syndrome.
- Author
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Liu JF, Dineen RA, Avula S, Chambers T, Dutta M, Jaspan T, MacArthur DC, Howarth S, Soria D, Quinlan P, Harave S, Ong CC, Mallucci CL, Kumar R, Pizer B, and Walker DA
- Subjects
- Adolescent, Algorithms, Cerebellar Diseases diagnostic imaging, Cerebellar Diseases epidemiology, Cerebellar Neoplasms complications, Cerebellar Neoplasms surgery, Cerebellum diagnostic imaging, Child, Child, Preschool, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Mutism diagnostic imaging, Mutism epidemiology, Observer Variation, Postoperative Complications diagnostic imaging, Postoperative Complications epidemiology, Predictive Value of Tests, Reproducibility of Results, Retrospective Studies, Risk Assessment, Risk Factors, United Kingdom epidemiology, Young Adult, Cerebellar Diseases diagnosis, Mutism diagnosis, Postoperative Complications diagnosis, Preoperative Period
- Abstract
Background: Despite previous identification of pre-operative clinical and radiological predictors of post-operative paediatric cerebellar mutism syndrome (CMS), a unifying pre-operative risk stratification model for use during surgical consent is currently lacking. The aim of the project is to develop a simple imaging-based pre-operative risk scoring scheme to stratify patients in terms of post-operative CMS risk., Methods: Pre-operative radiological features were recorded for a retrospectively assembled cohort of 89 posterior fossa tumour patients from two major UK treatment centers (age 2-23yrs; gender 28 M, 61 F; diagnosis: 38 pilocytic astrocytoma, 32 medulloblastoma, 12 ependymoma, 1 high grade glioma, 1 pilomyxoid astrocytoma, 1 atypical teratoid rhabdoid tumour, 1 hemangioma, 1 neurilemmoma, 2 oligodendroglioma). Twenty-six (29%) developed post-operative CMS. Based upon results from univariate analysis and C4.5 decision tree, stepwise logistic regression was used to develop the optimal model and generate risk scores., Results: Univariate analysis identified five significant risk factors and C4.5 decision tree analysis identified six predictors. Variables included in the final model are MRI primary location, bilateral middle cerebellar peduncle involvement (invasion and/or compression), dentate nucleus invasion and age at imaging >12.4 years. This model has an accuracy of 88.8% (79/89). Using risk score cut-off of 203 and 238, respectively, allowed discrimination into low (38/89, predicted CMS probability <3%), intermediate (17/89, predicted CMS probability 3-52%) and high-risk (34/89, predicted CMS probability ≥52%)., Conclusions: A risk stratification model for post-operative paediatric CMS could flag patients at increased or reduced risk pre-operatively which may influence strategies for surgical treatment of cerebellar tumours. Following future testing and prospective validation, this risk scoring scheme will be proposed for use during the surgical consenting process.
- Published
- 2018
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17. A cracking shot! depressed skull fracture sustained from a golf ball in a 16-year old.
- Author
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McGuinness RB, Jalloh I, and Macarthur DC
- Subjects
- Child, Humans, Image Processing, Computer-Assisted, Male, Skull Fracture, Depressed diagnostic imaging, Tomography, X-Ray Computed, Golf injuries, Skull Fracture, Depressed surgery
- Abstract
Depressed skull fractures sustained from golf balls are quite rare. We report such a case in a 16-year old, and demonstrate its appearance in a 3D CT reconstruction.
- Published
- 2017
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18. Insecticide resistance and cross-resistance development in Colorado potato beetle Leptinotarsa decemlineata Say (Coleoptera: Chrysomelidae) populations in Canada 2008-2011.
- Author
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Scott IM, Tolman JH, and MacArthur DC
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- Animals, Canada, Guanidines, Imidazoles, Insecticides, Larva physiology, Neonicotinoids, Nitro Compounds, Oxazines, Pyrazoles, Thiamethoxam, Thiazoles, ortho-Aminobenzoates, Coleoptera physiology, Insecticide Resistance
- Abstract
Background: A survey of insecticide resistance in over 150 Canadian populations of Colorado potato beetle was completed between 2008 and 2011. Three neonicotinoid and two anthranilic diamide insecticides were tested at a discriminating concentration (DC) with second-instar larvae in a leaf-disc bioassay., Results: The mean mortality for the imidacloprid (Admire) DC was 46-67% between 2008 and 2011 respectively. Over the 4 years, 10-46% and 26-40% of the populations were classified as resistant or showed reduced susceptibility to imidacloprid. The mean mortality for thiamethoxam (Actara) and clothianidin (Poncho/Titan) ranged from 56-76% in 2008 to 81-84% in 2010 for each insecticide respectively, indicating continuous susceptibility to clothianidin but reduced susceptibility to thiamethoxam. In 2008 and 2009, susceptibility to chlorantraniliprole (Coragen) was observed in 85% of populations. Similarly, cyantraniliprole (Cyazypyr) affected 93% of the 2009 and 74% of the 2010 populations. There was a significant (P < 0.05) and high positive correlation (R = 0.4-0.84) between the three neonicotinoids, indicating the potential for cross-resistance., Conclusions: The trend observed in decreasing susceptibility for thiamethoxam and clothianidin will continue unless resistance management practices are followed., (© 2014 Her Majesty the Queen in Right of Canada Pest Management Science © 2014 Society of Chemical Industry.)
- Published
- 2015
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19. Adjuvant chemotherapy for brain tumors delivered via a novel intra-cavity moldable polymer matrix.
- Author
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Rahman CV, Smith SJ, Morgan PS, Langmack KA, Clarke PA, Ritchie AA, Macarthur DC, Rose FR, Shakesheff KM, Grundy RG, and Ruman Rahman
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- Animals, Brain Neoplasms diagnostic imaging, Brain Neoplasms radiotherapy, Cell Death drug effects, Cell Line, Tumor, Chemotherapy, Adjuvant, Etoposide pharmacology, Etoposide therapeutic use, Humans, Magnetic Resonance Imaging, Male, Mice, Mice, Nude, Polylactic Acid-Polyglycolic Acid Copolymer, Sheep, Tomography, X-Ray Computed, Xenograft Model Antitumor Assays, Brain Neoplasms drug therapy, Drug Delivery Systems, Lactic Acid chemistry, Polyethylene Glycols chemistry, Polyglycolic Acid chemistry
- Abstract
Introduction: Polymer-based delivery systems offer innovative intra-cavity administration of drugs, with the potential to better target micro-deposits of cancer cells in brain parenchyma beyond the resected cavity. Here we evaluate clinical utility, toxicity and sustained drug release capability of a novel formulation of poly(lactic-co-glycolic acid) (PLGA)/poly(ethylene glycol) (PEG) microparticles., Methods: PLGA/PEG microparticle-based matrices were molded around an ex vivo brain pseudo-resection cavity and analyzed using magnetic resonance imaging and computerized tomography. In vitro toxicity of the polymer was assessed using tumor and endothelial cells and drug release from trichostatin A-, etoposide- and methotrexate-loaded matrices was determined. To verify activity of released agents, tumor cells were seeded onto drug-loaded matrices and viability assessed., Results: PLGA/PEG matrices can be molded around a pseudo-resection cavity wall with no polymer-related artifact on clinical scans. The polymer withstands fractionated radiotherapy, with no disruption of microparticle structure. No toxicity was evident when tumor or endothelial cells were grown on control matrices in vitro. Trichostatin A, etoposide and methotrexate were released from the matrices over a 3-4 week period in vitro and etoposide released over 3 days in vivo, with released agents retaining cytotoxic capabilities. PLGA/PEG microparticle-based matrices molded around a resection cavity wall are distinguishable in clinical scanning modalities. Matrices are non-toxic in vitro suggesting good biocompatibility in vivo. Active trichostatin A, etoposide and methotrexate can be incorporated and released gradually from matrices, with radiotherapy unlikely to interfere with release., Conclusion: The PLGA/PEG delivery system offers an innovative intra-cavity approach to administer chemotherapeutics for improved local control of malignant brain tumors.
- Published
- 2013
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20. CD105 (Endoglin) exerts prognostic effects via its role in the microvascular niche of paediatric high grade glioma.
- Author
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Smith SJ, Tilly H, Ward JH, Macarthur DC, Lowe J, Coyle B, and Grundy RG
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- Adolescent, Brain Neoplasms mortality, Child, Child, Preschool, Cohort Studies, Endoglin, Female, Gene Expression physiology, Glioma mortality, Humans, Infant, Infant, Newborn, Kaplan-Meier Estimate, Ki-67 Antigen metabolism, Male, Platelet Endothelial Cell Adhesion Molecule-1 metabolism, Vascular Endothelial Growth Factor A metabolism, Young Adult, Antigens, CD metabolism, Brain Neoplasms diagnosis, Glioma diagnosis, Neovascularization, Pathologic metabolism, Receptors, Cell Surface metabolism
- Abstract
Paediatric high grade glioma (pHGG) (World Health Organisation astrocytoma grades III and IV) remains poor prognosis tumours, with a median survival of only 15 months following diagnosis. Current investigation of anti-angiogenic strategies has focused on adult glioblastoma multiforme (GBM) with phase III trials targeting vascular endothelial growth factor continuing. In this study we investigated whether the degree of vascularity correlated with prognosis in a large cohort of pHGG (n = 150) and whether different vessel markers carried different prognostic value. We found that CD105 (endoglin) had a strongly significant association with poor prognosis on multivariate analysis (p = <0.001). Supervised hierarchical clustering of genome wide gene expression data identified 13 genes associated with differential degrees of vascularity in the cohort. The novel angiogenesis-associated genes identified in this analysis (including MIPOL-1 and ENPP5) were validated by realtime polymerase chain reaction. We also demonstrate that CD105 positive blood vessels associate with CD133 positive tumour cells and that a proportion of CD105 positive vessel cells demonstrates co-positivity for CD133, suggesting that the recently described phenomenon of vasculogenic mimicry occurs in pHGG. Together, the data suggest that targeting angiogenesis, and in particular CD105, is a valid therapeutic strategy for pHGG.
- Published
- 2012
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21. Recapitulation of tumor heterogeneity and molecular signatures in a 3D brain cancer model with decreased sensitivity to histone deacetylase inhibition.
- Author
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Smith SJ, Wilson M, Ward JH, Rahman CV, Peet AC, Macarthur DC, Rose FR, Grundy RG, and Rahman R
- Subjects
- Brain Neoplasms metabolism, Cell Line, Tumor, Cell Proliferation, Cluster Analysis, Extracellular Matrix metabolism, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Metabolome, Phenotype, Primary Cell Culture, Spheroids, Cellular, Tumor Cells, Cultured, Tumor Microenvironment, Antineoplastic Agents pharmacology, Brain Neoplasms genetics, Brain Neoplasms pathology, Drug Resistance, Neoplasm, Histone Deacetylase Inhibitors pharmacology
- Abstract
Introduction: Physiologically relevant pre-clinical ex vivo models recapitulating CNS tumor micro-environmental complexity will aid development of biologically-targeted agents. We present comprehensive characterization of tumor aggregates generated using the 3D Rotary Cell Culture System (RCCS)., Methods: CNS cancer cell lines were grown in conventional 2D cultures and the RCCS and comparison with a cohort of 53 pediatric high grade gliomas conducted by genome wide gene expression and microRNA arrays, coupled with immunohistochemistry, ex vivo magnetic resonance spectroscopy and drug sensitivity evaluation using the histone deacetylase inhibitor, Vorinostat., Results: Macroscopic RCCS aggregates recapitulated the heterogeneous morphology of brain tumors with a distinct proliferating rim, necrotic core and oxygen tension gradient. Gene expression and microRNA analyses revealed significant differences with 3D expression intermediate to 2D cultures and primary brain tumors. Metabolic profiling revealed differential profiles, with an increase in tumor specific metabolites in 3D. To evaluate the potential of the RCCS as a drug testing tool, we determined the efficacy of Vorinostat against aggregates of U87 and KNS42 glioblastoma cells. Both lines demonstrated markedly reduced sensitivity when assaying in 3D culture conditions compared to classical 2D drug screen approaches., Conclusions: Our comprehensive characterization demonstrates that 3D RCCS culture of high grade brain tumor cells has profound effects on the genetic, epigenetic and metabolic profiles of cultured cells, with these cells residing as an intermediate phenotype between that of 2D cultures and primary tumors. There is a discrepancy between 2D culture and tumor molecular profiles, and RCCS partially re-capitulates tissue specific features, allowing drug testing in a more relevant ex vivo system.
- Published
- 2012
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22. Pediatric high-grade glioma: identification of poly(ADP-ribose) polymerase as a potential therapeutic target.
- Author
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Smith SJ, Long A, Barrow JH, Macarthur DC, Coyle B, and Grundy RG
- Subjects
- Adolescent, Adult, Apoptosis Inducing Factor metabolism, Brain Neoplasms mortality, Brain Neoplasms pathology, Child, Child, Preschool, Female, Glioma mortality, Glioma pathology, Humans, Immunoenzyme Techniques, Infant, Infant, Newborn, Male, Neoplasm Grading, Prognosis, Retrospective Studies, Survival Rate, Tissue Array Analysis, Young Adult, Brain Neoplasms enzymology, Glioma enzymology, Poly(ADP-ribose) Polymerases metabolism
- Abstract
Pediatric high-grade gliomas (World Health Organization grades III and IV astrocytomas) remain tumors with a very poor prognosis for which novel therapeutic strategies are needed. Poly(ADP-ribose) polymerase (PARP) is known to have multiple functions in tumors, including single-strand DNA repair and induction of caspase-independent apoptosis. PARP has been suggested as a therapeutic target in adult malignancies, and this study examines whether it could also be a potential target in pediatric high-grade glioma. Tissue microarrays containing 150 formalin-fixed pediatric high-grade gliomas were examined by immunohistochemistry for levels of PARP and expression of apoptosis inducing factor (AIF). Full retrospective clinical and survival data were available for this cohort. Stratification and statistical analysis was performed to assess the effect of PARP status on prognosis. The level of PARP immunopositivity had a statistically significant inverse correlation (P = .019) with survival in supratentorial pediatric high-grade glioma. AIF staining was notable for its absence in the majority of tumors but with moderate levels of expression in surrounding normal brain. PARP is expressed at high levels in many pediatric high-grade gliomas, and in these tumors, the ability of PARP to activate AIF appears to have been lost. PARP may therefore represent a promising therapeutic target for these lesions and warrants evaluation in clinical trials.
- Published
- 2011
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23. An unusual presentation of colloid cyst--implications for lifestyle advice.
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Sharp MC and MacArthur DC
- Subjects
- Adult, Cerebral Ventricle Neoplasms physiopathology, Colloid Cysts physiopathology, Headache etiology, Humans, Male, Radiography, Risk Reduction Behavior, Risk-Taking, Acceleration adverse effects, Cerebral Ventricle Neoplasms diagnostic imaging, Colloid Cysts diagnostic imaging, Headache diagnostic imaging, Leisure Activities
- Abstract
Colloid cysts are rare intracranial neoplasms which typically present with headaches. There is risk of neurological deterioration or death due to acute hydrocephalus. We report a case of colloid cyst presenting after a sudden acceleration/deceleration force from a theme park ride, highlighting the importance of lifestyle advice in these patients.
- Published
- 2011
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24. Never go to sleep on undrained pus: a retrospective review of surgery for intraparenchymal cerebral abscess.
- Author
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Smith SJ, Ughratdar I, and MacArthur DC
- Subjects
- Adolescent, Adult, Aged, Aspergillus isolation & purification, Brain Abscess diagnosis, Brain Abscess drug therapy, Child, Child, Preschool, Craniotomy, Diffusion Magnetic Resonance Imaging methods, Female, Glasgow Outcome Scale, Humans, Male, Middle Aged, Reoperation statistics & numerical data, Retrospective Studies, Streptococcus milleri Group isolation & purification, Time Factors, Tomography, X-Ray Computed, Treatment Outcome, Trephining, Young Adult, Anti-Infective Agents therapeutic use, Brain Abscess surgery, Drainage methods
- Abstract
Cerebral abscess is an emergency requiring urgent drainage via craniotomy or burrhole aspiration. We examine whether initial method of drainage affects outcome and important characteristics in patients with cerebral abscess. This is a retrospective analysis of 62 patients operated on in our unit with a loculated infected cerebral collection in the years 2003-2007 inclusive. Full statistical analysis was performed using data appropriate tests. Burrhole and craniotomy groups were evenly matched with no difference in any demographic factors. Surgical method made no difference to rate of re-operation (p = 0.276), antibiotic duration (p = 0.648), discharge GCS (p = 0.509), length of stay (p = 0.647) or GOS (p = 0.968). There was a trend to worsened outcome with delay to surgery (p = 0.132) with delayed patients requiring longer hospital stays (p < or = 0.005). Patients requiring a longer antibiotic duration had worse outcomes (p < or = 0.005). Surgical method did not have a significant effect on outcome, so burrhole aspiration with its advantages in terms of speed and scale of surgery should be strongly considered. Delay had an adverse affect, so operation should be as expeditious as possible whenever the differential diagnosis includes abscess, diagnosis of which may be aided by advanced magnetic resonance imaging techniques.
- Published
- 2009
- Full Text
- View/download PDF
25. Atypical meningiomas: WHO moved the goalposts?
- Author
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Smith SJ, Boddu S, and Macarthur DC
- Subjects
- Female, Humans, Male, Meningeal Neoplasms classification, Meningeal Neoplasms epidemiology, Meningioma classification, Meningioma epidemiology, Neoplasm Staging methods, Retrospective Studies, World Health Organization, Meningeal Neoplasms pathology, Meningioma pathology
- Abstract
The histological grading of meningiomas underwent substantial revision and standardization in a WHO review of 2000. Prior to this the histological definition of atypical and malignant meningiomas was less tightly defined. We conducted a retrospective analysis of all meningiomas operated on between 1993 and 2003 in our unit (n=565), to assess whether the WHO changes had altered the proportion of tumours diagnosed as atypical. The percentage of tumours graded WHO II (atypical meningiomas) has increased significantly since these changes were adopted (18.3-23.1%, p=0.0408). We also examined the epidemiology of meningioma, finding that previous irradiation is associated with atypical meningiomas (p=0.038) and surgeons find that complete excision is also more difficult with atypical tumours (p=0.010), reporting poorer Simpson grades intraoperatively before the tumour grade is known. The increase in atypical lesions caused by the grading changes may lead to a corresponding increase in the numbers of patients referred for radiotherapy/radiosurgery, and we examine the evidence base for this strategy and whether our experience is replicated in other units.
- Published
- 2007
- Full Text
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26. Stereotactic brain biopsy: An audit of sampling reliability in a clinical case series.
- Author
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Shastri-Hurst N, Tsegaye M, Robson DK, Lowe JS, and Macarthur DC
- Subjects
- Humans, Sensitivity and Specificity, Biopsy methods, Brain pathology, Brain Neoplasms pathology, Glioblastoma pathology, Stereotaxic Techniques standards
- Abstract
Stereotactic brain biopsy is the current gold standard procedure to obtain a neuropathological diagnosis. An audit of 207 stereotactic cases, between January 1997 and December 2000 was carried out. The aim was to determine the optimum number of target sites required to make the final diagnosis and thereby set up recommendations for future practice. The overall diagnostic success rate was 89.3%. A significant positive correlation between the number of targets taken and the probability of achieving the final diagnosis was seen. In a subset of glioblastoma cases 96.1% of the tumours could have been confidently diagnosed on the basis of any two of the targets chosen, although often more targets were taken than this. The recommendations made by the audit were: (i) in cases where it is suspected the lesion does not require grading, one target site should be taken and further sites should only be taken if the first proves to be non diagnostic; (ii) in suspected glial series tumours, two targets should be routinely taken, with further sites taken only if these prove inconclusive on intraoperative smear.
- Published
- 2006
- Full Text
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27. The role of neuroendoscopy in the management of brain tumours.
- Author
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Macarthur DC, Buxton N, Punt J, Vloeberghs M, and Robertson IJ
- Subjects
- Adolescent, Adult, Aged, Brain Neoplasms complications, Child, Child, Preschool, Female, Humans, Hydrocephalus complications, Infant, Male, Middle Aged, Neurosurgical Procedures adverse effects, Treatment Outcome, Brain Neoplasms surgery, Endoscopy methods
- Abstract
Neuroendoscopy is increasingly used in the management of brain tumours and tumour related hydrocephalus and this study reviews the efficacy of neuroendoscopic interventions in this unit in patients with brain tumours. A series of 87 neuroendoscopic operations carried out in 77 patients with brain tumours over a 6-year period is reported. The age range of the patients was from 5 months to 70 years (median 13 years). In 56 cases (64%) presentation was with a newly-diagnosed tumour and hydrocephalus. The majority of the remaining patients had varying degrees of worsening hydrocephalus on the background of a previously diagnosed tumour. Neuroendoscopic third ventriculostomy (NTV) was successful in relieving hydrocephalus in the short term in 63/66 cases (95%) and in the longer term in 55/66 cases (83%). Neuroendoscopic tumour biopsies were successful in providing a tissue diagnosis in 17/28 cases (61%) and four extensive and three partial resections of tumour were carried out. There were two deaths within 30 days of the procedure with only one of these, secondary to intraventricular haemorrhage, directly related to neuroendoscopy. Few significant complications were noted otherwise. For selected intraventricular and paraventricular tumours neuroendoscopy offers the opportunity to combine relief of hydrocephalus with tumour biopsy and sampling of CSF in a single procedure.
- Published
- 2002
- Full Text
- View/download PDF
28. 'Mind the gap': resorption of a bone flap stored subcutaneously for 6 months.
- Author
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Yap C, Macarthur DC, and Hope DT
- Subjects
- Adult, Bone Resorption diagnostic imaging, Craniocerebral Trauma diagnostic imaging, Craniocerebral Trauma surgery, Hematoma, Subdural diagnostic imaging, Hematoma, Subdural surgery, Humans, Male, Radiography, Skull diagnostic imaging, Bone Resorption physiopathology, Surgical Flaps
- Published
- 2002
- Full Text
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29. The management of brain tumours.
- Author
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Macarthur DC and Buxton N
- Subjects
- Humans, Brain Neoplasms therapy
- Abstract
Current knowledge on the biology and clinical features of brain tumours is reviewed with particular reference to the most commonly occurring tumours - gliomas, meningiomas and metastases. Unfortunately, the enormous increase in understanding of the biology of these tumours over recent years has not, as yet, been paralleled by advances in treatment or improvements in clinical outcome. Developing adjuvant therapies, ranging from novel means of delivery of radiotherapy and new chemotherapy agents to gene therapy and anti-angiogenic agents, are currently being explored and offer some hope for improvement in our ability to treat these tumours over the next few decades.
- Published
- 2001
30. The effectiveness of neuroendoscopic interventions in children with brain tumours.
- Author
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Macarthur DC, Buxton N, Vloeberghs M, and Punt J
- Subjects
- Adolescent, Biopsy, Brain pathology, Brain Neoplasms complications, Cerebrospinal Fluid Shunts, Child, Child, Preschool, Female, Humans, Hydrocephalus etiology, Infant, Male, Neurosurgical Procedures adverse effects, Neurosurgical Procedures instrumentation, Retrospective Studies, Treatment Outcome, Brain surgery, Brain Neoplasms surgery, Endoscopy adverse effects, Endoscopy methods, Hydrocephalus surgery, Neurosurgical Procedures methods
- Abstract
Object: The purpose of this study was to review the efficacy of neuroendoscopic interventions in children with brain tumours and tumour-related hydrocephalus., Methods: In all, 61 consecutive neuroendoscopic operations carried out in 53 children with brain tumours over a 6-year period were reviewed. The patients ranged in age from 5 months to 18 years (median 9 years). Forty of 61 presentations were with a newly diagnosed tumour and hydrocephalus - the remainder predominantly had a known tumour and worsening hydrocephalus., Conclusions: Neuroendoscopic third ventriculostomy (NTV) successfully relieved hydrocephalus in the short term in 45 of 47 cases and in the longer term in 39 of 47 cases. Neuroendoscopic biopsy provided definitive tissue diagnosis in 10 of 16 cases and 5 tumours were resected. There was 1 postoperative death, which not directly related to the neuroendoscopy and few significant complications otherwise. Neuroendoscopic methods allow effective immediate and longer term control of hydrocephalus as well as the opportunity for CSF sampling and tumour biopsy in selected cases.
- Published
- 2001
- Full Text
- View/download PDF
31. Neurological deterioration years after closure of myelomeningocoele - 'the second lesion'.
- Author
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Macarthur DC, Punt JA, Spencer M, Douglas DL, White BD, and Holland IM
- Subjects
- Adult, Dermoid Cyst etiology, Dermoid Cyst surgery, Diagnosis, Differential, Disease Progression, Follow-Up Studies, Humans, Low Back Pain etiology, Lumbar Vertebrae, Magnetic Resonance Imaging methods, Male, Meningomyelocele diagnosis, Meningomyelocele surgery, Neuroectodermal Tumors diagnosis, Severity of Illness Index, Spinal Cord Neoplasms etiology, Spinal Cord Neoplasms surgery, Time Factors, Dermoid Cyst diagnosis, Meningomyelocele complications, Spinal Cord Neoplasms diagnosis
- Published
- 2001
- Full Text
- View/download PDF
32. Third ventricular cysts and membranes unsuspected on conventional CT and MRI.
- Author
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MacArthur DC, Robertson IJ, and Punt JA
- Subjects
- Adult, Cysts complications, Female, Humans, Hydrocephalus etiology, Magnetic Resonance Imaging, Male, Middle Aged, Tomography, X-Ray Computed, Treatment Outcome, Ventriculostomy, Cysts surgery, Hydrocephalus surgery, Third Ventricle surgery
- Abstract
Three cases are presented of symptomatic cysts or membranes within the third ventricle interfering with CSF flow and presenting as non-communicating triventricular hydrocephalus. None was visible on conventional CT or MRI, two being discovered at neuroendoscopy and one only with a specific MRI sequence designed to show CSF partitioning.
- Published
- 2000
- Full Text
- View/download PDF
33. Can experimental models of rodent implantation glioma be improved? A study of pure and mixed glioma cell line tumours.
- Author
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Whittle IR, Macarthur DC, Malcolm GP, Li M, Washington K, and Ironside JW
- Subjects
- Animals, Brain Neoplasms physiopathology, Disease Models, Animal, Glioma physiopathology, Immunohistochemistry, Male, Mixed Tumor, Malignant physiopathology, Neoplasms, Experimental physiopathology, Rats, Rats, Wistar, Tumor Cells, Cultured, Brain Neoplasms pathology, Glioma pathology, Mixed Tumor, Malignant pathology, Neoplasm Transplantation methods, Neoplasms, Experimental pathology
- Abstract
To evaluate the hypothesis that co-implantation of different rodent glioma cell lines might result in experimental brain tumours that more closely resemble human gliomas the neuropathology and immunocytochemical features of implantation gliomas derived from single cell lines (C6, A15A5, F98), two cell lines admixed 50:50 prior to implantation (C6 + F98 and C6 + A15A5) and three cell lines equally admixed (C6 + A15A5 + F98) was studied in the adult Wistar rat. Tumours grew consistently following implantation of the single and the two admixed cell lines, however tumour growth following triple mix implantation was considerably and consistently impaired. The tumours derived from admixed cell lines showed regional heterogeneity with areas characteristic of both the primary cell lines. Foci of lymphocytic infiltrates, tumoural necrosis, often with pseudopallisading, and peritumoural edema were consistent features of all tumours. Limited parenchymal and more extensive perivascular tumoural invasion was seen predominantly in tumours containing the C6 cell line. There were no significant differences in GFAP, vimentin and HSP70 staining between the mixed tumours, although the pure F98 and A15A5 tumours were, unlike the pure C6 gliomas, S-100 negative. Using PCNA expression as a measure of the tumour proliferation all except the tumours derived from the three cell lines mix, which had a staining index of 7-10%, had focal staining indices in viable tumour of between 40-80%. There was focal positive staining in both perilesional brain and in regions of all tumours for the macrophage markers ED-1 and ED-2. None of the three cell lines stained in vitro for either ED1 and ED2 but all were constitutively positive in vitro for OX-6, a proposed marker for antigen presenting cells. The macrophage and lymphocytic response suggest a vigorous but largely ineffective immunological response had been mounted against all tumours. The consistent failure of the triple mix tumours to grow is unexplained. This work has shown the feasibility of producing 'mixed' cell line experimental gliomas by combining two cell lines at the time of innoculation. However, the relative failure to produce (i) mixed tumours that have properties not inherent to either parent cell line and (ii) implantation glioma with three cell lines suggest there are limits to this approach. Admixture of cell lines at the time of implantation therefore does not make experimental glioma models that more closely resemble natural gliomas, and also has some particular disadvantages. This experimental approach is therefore not recommended for use in the study of tumour biology and in evaluating the effectiveness of novel therapies.
- Published
- 1998
- Full Text
- View/download PDF
34. Avoidable deaths still occur after large bowel surgery. Scottish Audit of Surgical Mortality, Royal College of Surgeons of Edinburgh.
- Author
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Macarthur DC, Nixon SJ, and Aitken RJ
- Subjects
- Adult, Aged, Aged, 80 and over, Cause of Death, Cohort Studies, Colorectal Surgery, Decision Making, Diagnostic Errors, Female, Hospital Mortality, Humans, Male, Medical Audit, Middle Aged, Pilot Projects, Scotland epidemiology, Surgical Wound Dehiscence mortality, Colonic Diseases mortality, Colonic Diseases surgery
- Abstract
Background: Postoperative death following large bowel surgery is relatively infrequent and no large study has analysed the cause of all deaths comprehensively and critically., Methods: In-hospital deaths following large bowel surgery in South-East Scotland were reviewed by independent assessors. The audit was confidential but not anonymous. Independent assessors' reports were returned to consultants., Results: The audit documented 187 deaths. The independent assessors noted an adverse event in 78 patients (42 per cent). Twenty-six deaths (14 per cent) occurred following an anastomotic leak. A further 43 deaths (23 per cent) occurred because surgery was delayed (17) or there was undue delay in making the initial diagnosis (12) or recognizing a developing complication (14). Consultants operated on only half the patients classed as American Society of Anesthesiologists grade IV or V, or undergoing a second or subsequent operation., Conclusion: Half the patients dying in this study had identifiable deficiencies in their management. There is a clear need for greater consultant input with critically ill patients.
- Published
- 1998
- Full Text
- View/download PDF
35. Herniography for groin pain of uncertain origin.
- Author
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Macarthur DC, Grieve DC, Thompson AM, Greig JD, and Nixon SJ
- Subjects
- Adult, Aged, Female, Hernia, Femoral complications, Hernia, Femoral diagnostic imaging, Hernia, Inguinal complications, Humans, Male, Middle Aged, Pain diagnostic imaging, Radiography, Hernia, Inguinal diagnostic imaging, Inguinal Canal diagnostic imaging, Pain etiology
- Published
- 1997
- Full Text
- View/download PDF
36. Nail gun injury to the brain: an unusual case of suicide.
- Author
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Viswanathan R, MacArthur DC, and Whittle IR
- Subjects
- Humans, Male, Middle Aged, Brain Injuries etiology, Construction Materials, Firearms, Suicide, Wounds, Penetrating etiology
- Abstract
An unusual case of fatal suicidal craniocerebral penetrating injury due to a nail gun is described. The victim, a 52 year old joiner experienced in the use of nail drivers, shot himself just above the forehead in the midline, driving the nail through his hypothalamus and midbrain. Death was delayed by nearly 24 hours.
- Published
- 1994
- Full Text
- View/download PDF
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