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P Bullock

Publications and source records attributed to P Bullock.

At least 19 recordsLinked to original sources
PubMed2006

Giant traumatic pseudoaneurysm of the superficial temporal artery: treatment challenges and case review.

Traumatic pseudoaneurysms of the superficial temporal artery are uncommon. They present to a variety of specialities - orthopaedics, ear, nose and throat, neurosurgery, maxillofacial, plastic surgery, vascular surgery and dermatology. Experience managing these lesions is therefore limited and diluted. We present a case of a giant, traumatic pseudoaneurysm of the superficial temporal artery, which required the unusual approach of staged surgical excision.

Accidental Falls↗
PubMed2004

Comparison of alamar blue and MTT assays for high through-put screening.

The performance of alamar blue and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) cell viability assays in a high through-put format were compared. A total of 117 drugs chosen for their wide range of therapeutic areas were screened at 10 microM using both assays in human hepatoma cell line HepG2. Except for terfenadine and astemizole, which performed consistently in both assays, the alamar blue assay was slightly more sensitive than the MTT assay for most compounds. The MTT assay was less sensitive detecting an effect for daunorubicin and trifluoperazine. Seven drugs, astemizole, daunorubicin, ellipticine, fluphenazine, terfenadine, thioridazine and trifluoperazine, had percent viability results of 55% or less in the alamar blue assay at the single point screen. These were re-tested in both assays for reconfirmation of cytotoxicity and determination of the EC50 values. Except for daunorubicin, the EC50 values were comparable in both assays. Based on these results and the Z'-factor assessment of assay quality, both assays provided useful information to identify in vitro cytotoxic drugs at early stages of drug candidate selection. However, careful interpretation of data is warranted due to the possibility of false positive or negative results caused by inducers and/or inhibitors of metabolic enzymes that are responsible for transformation of cell toxicity end points, as we demonstrated using dicumarol.

Carcinoma, Hepatocellular↗
PubMed2003

ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties.

Herpes simplex virus type-1 (HSV1) in which the neurovirulence factor ICP34.5 is inactivated has been shown to direct tumour-specific cell lysis in several tumour models. Such viruses have also been shown to be safe in Phase I clinical trials by intra-tumoral injection in glioma and melanoma patients. Previous work has used serially passaged laboratory isolates of HSV1 which we hypothesized may be attenuated in their lytic capability in human tumour cells as compared to more recent clinical isolates. To produce ICP34.5 deleted HSV with enhanced oncolytic potential, we tested two clinical isolates. Both showed improved cell killing in all human tumour cell lines tested compared to a laboratory strain (strain 17+). ICP34.5 was then deleted from one of the clinical isolate strains (strain JS1). Enhanced tumour cell killing with ICP34.5 deleted HSV has also been reported by the deletion of ICP47 by the up-regulation of US11 which occurs following this mutation. Thus to further improve oncolytic properties, ICP47 was removed from JS1/ICP34.5-. As ICP47 also functions to block antigen processing in HSV infected cells, this mutation was also anticipated to improve the immune stimulating properties of the virus. Finally, to provide viruses with maximum oncolytic and immune stimulating properties, the gene for human or mouse GM-CSF was inserted into the JS1/34.5-/47- vector backbone. GM-CSF is a potent immune stimulator promoting the differentiation of progenitor cells into dendritic cells and has shown promise in clinical trials when delivered by a number of means. Combination of GM-CSF with oncolytic therapy may be particularly effective as the necrotic cell death accompanying virus replication should serve to effectively release tumour antigens to then induce a GM-CSF-enhanced immune response. This would, in effect, provide an in situ, patient-specific, anti-tumour vaccine. The viruses constructed were tested in vitro in human tumour cell lines and in vivo in mice demonstrating significant anti-tumour effects. These were greatly improved compared to viruses not containing each of the modifications described. In vivo, both injected and non-injected tumours showed significant shrinkage or clearance and mice were protected against re-challenge with tumour cells. The data presented indicate that JS1/ICP34.5-/ICP47-/GM-CSF acts as a powerful oncolytic agent which may be appropriate for the treatment of a number of solid tumour types in man.

Animals↗
PubMed2001

Evening shift.

Explore the source record for details and available documents.

Emergency Nursing↗
PubMed2000

Positron emission tomography in imaging spinal cord tumors.

The ability of positron emission tomography (PET) to detect spinal cord tumors was studied prospectively in 14 patients presenting over a 5-year period. Abnormal uptake by [18F]-fluorodeoxyglucose (FDG) or 11C-methionine was detected in all except one. These data were assessed in relation to magnetic resonance imaging (MRI) findings with regard to tumor type and extent preoperatively, findings at operation, and subsequent clinical course. The group consisted of six astrocytomas, five ependymomas, one mixed ependymoma and astrocytoma, one schwannoma, and one ganglioglioma, all confirmed histologically. This is the largest study comparing spinal PET to MRI. Accurate preoperative correlation between PET and MRI was found in all eight patients scanned at first presentation. The PET uptake was in keeping with the low-grade histology of the tumors. Postoperatively, PET and MRI findings were in agreement in nine patients. In eight of these the findings were in keeping with the subsequent clinical course. In three patients, however, the PET findings were at variance with the clinical course and MRI findings. In one, persistent FDG uptake after radiotherapy was seen where there was subsequent tumor resolution. In two patients with low-grade astrocytomas, scanned with FDG and 11C-methionine, respectively, tracer was not taken up by residual tumor. In this small group of patients, PET did not provide additional useful information. This could be because all tumors studied were low grade and the limited spatial resolution of PET does not lend itself to imaging small spinal cord tumors. The prospective study of larger numbers of patients with a wider range of tumor types is required, but this might be difficult to achieve given the rarity of spinal cord tumors.

Adolescent↗
PubMed1999

Salmonella meningitis and multiple cerebral abscesses in an infant.

The history of a 4-week-old infant with meningitis and multiple cerebral abscesses caused by Salmonella enteritidis is reported. Management included successful treatment with a prolonged course of antibiotics, including ciprofloxacin, neurosurgical drainage and long-term immunoglobulin supplements. No adverse effects of joint toxicity were detected.

Amoxicillin↗
PubMed1999

Influence of extracellular matrix overlay and medium formulation on the induction of cytochrome P-450 2B enzymes in primary cultures of rat hepatocytes.

The effect of medium formulation, composition of extracellular matrix overlay, and culture dish material on liver microsomal cytochrome P-450 (CYP) 2B induction by phenobarbital (PB) was investigated in primary cultures of rat hepatocytes. When hepatocytes were maintained on Permanox dishes with an overlay of either collagen (type I) or Matrigel, Williams' E medium was superior to other medium formulations in terms of the magnitude of induction of CYP2B on a per milligram microsomal protein basis. Modified Chee's medium (MCM) and hepatocyte culture medium were intermediate in their capacity to sustain induction of CYP2B by PB, and Dulbecco's modified Eagle's medium was slightly less effective. The overall induction of CYP2B activity by PB was, on average, 50% lower in hepatocytes cultured on polystyrene dishes (LUX). Little or no difference was observed between hepatocytes overlaid with collagen and those overlaid with Matrigel. MCM was superior to Williams' E medium in terms of the yield of microsomal protein and the ultrastructural features of the hepatocyte monolayers. CYP2B induction by PB was optimal after 3 days of treatment in either medium. CYP1A, CYP3A, and CYP4A activities could be induced in vitro by prototypical inducing agents in hepatocytes cultured on Permanox dishes with MCM and a Matrigel overlay to comparable levels observed in vivo. The results of these studies show that medium formulation and culture vessel material, but not the type of extracellular matrix overlay, have significant effects on the induction of CYP enzymes in cultured rat hepatocytes maintained in a sandwich configuration.

Animals↗
PubMed1998

Recognition memory and memory for order in script-based stories following frontal lobe excisions.

Memory for stories was investigated in 25 patients with frontal lobe excisions and 25 control subjects. The subjects were presented with three different story types that either conformed to a well-known script, contained the same elements as a script but in a randomised order, or described a novel event. Subjects were asked to perform a test of recognition memory and memory for order on words presented in each story. The frontal lobe patients were unimpaired on the recognition memory test for salient words taken from each story. However, an impairment was observed in the frontal patients when they were asked to order the words taken from the novel story only. This deficit was no longer seen when the subjects were required to order sentences describing the key events in the story. These findings help to elucidate the role of the frontal lobes in memory for order information.

Adult↗
PubMed1997

The effect of goal-subgoal conflict on planning ability after frontal- and temporal-lobe lesions in humans.

Twenty-one patients with unilateral prefrontal cortical neurosurgical lesions (11 left and 10 right) and 38 patients with unilateral temporal lobectomy (19 left and 19 right) were compared to 44 matched control subjects on their performance on the 3-D Computerized Tower of Hanoi (3-D CTOH) test. The problems were split into those with or without a significant goal-subgoal conflict determined by whether the correct first move in each problem took the subject apparently away or towards the final goal state. The left frontal lesion and right temporal lobectomy groups were significantly impaired on problems with goal-subgoal conflicts. In the left frontal group, this deficit was confined to earlier four-move problems, whereas the right temporal group showed a more general deficit on later five-move problems. The left frontal lesion deficit is explained in terms of an inability to inhibit the response compatible with achieving a final goal, whereas the impairment in the right lesion group was related to a specific impairment in spatial memory.

Adult↗
PubMed1996

Spatial working memory and strategy formation in patients with frontal lobe excisions.

Spatial working memory was investigated in 20 patients with unilateral neurosurgical excisions of the frontal cortex (UFL), nine with right (RFL) and eleven with left lesions (LFL), comparing their performance to a matched control group. Spatial memory was tested using the Executive Golf Task, a test that also measures spatial strategy formation. Overall the UFL were significantly impaired, the greatest impairment being found in the RFL group. The difference between the RFL and LFL groups was abolished when a measure of strategy formation was used as a covariate in the analysis. A further test of spatial working memory, the Owl Spatial Working Memory Task, which prevents the use of a spatial strategy, showed a significant and equivalent impairment in both the RFL and LFL patients. The data are consistent with neuropsychological and functional neuroimaging investigations supporting the role of the pre-frontal cortex in spatial working memory.

Adult↗
PubMed1996

Why are brain tumours still being missed?

The prediagnosis period of 74 children with primary brain tumours was assessed to examine their presentation and reasons for any delay in diagnosis. Medical case notes were reviewed and parents were interviewed and asked to complete psychological questionnaires. Mean (SD) duration of clinical history was 20.0 (29.1) weeks. Most common symptoms were vomiting (65%) and headache (64%). Only 34% of headaches were always associated with vomiting and only 28% occurred 'early morning'. Changes in the child's personality (47%) were also common. The average number of consultations before diagnosis was 4.6. Migraine was diagnosed in 24% of children and a psychological aetiology in 15%. One quarter of the children had altered levels of consciousness on arrival at the unit. Results indicate that delay in diagnosis still occurs, despite strong parental concern. The nonspecificity of symptoms and a high incidence of psychological symptoms may confound the clinical picture and are considered along with other possible contributory factors.

Adolescent↗
PubMed1996

Difficulties in diagnosing intrinsic spinal cord tumours.

Thirteen children with intrinsic spinal cord tumours were seen between 1984 and 1995. In only one was this the presumptive diagnosis at referral, despite a high incidence of characteristic features. Eight had presented to their local paediatrician, four to local orthopaedic teams, and one to a general surgeon. Eleven had back pain. Eleven had either spinal curvature or change in gait. The interval between onset of symptoms and diagnosis ranged from one week to six years, with a mean of 17.5 months. In nine children symptoms had been present for four or more months. In nine, unrewarding investigations had been carried out. This paper highlights typical presenting features of these tumours and how earlier diagnosis can be achieved.

Back Pain↗
PubMed1995

Rat serum carboxylesterase. Cloning, expression, regulation, and evidence of secretion from liver.

Multiple forms of carboxylesterase have been identified in rat liver, and five carboxylesterases (designated hydrolases A, B, C, S, and egasyn) have been cloned. Hydrolases A, B, C, and egasyn all have a C-terminal consensus sequence (HXEL) for retaining proteins in the endoplasmic reticulum, and these carboxylesterases are found in rat liver microsomes. In contrast, hydrolase S lacks this C-terminal consensus sequence and is presumed to be secreted. In order to test this hypothesis, a polyclonal antibody was raised against recombinant hydrolase S from cDNA-directed expression in Escherichia coli. In addition to hydrolases A, B, and C (57-59 kDa), this antibody recognized a 67-kDa protein in rat liver microsomes and a 71-kDa protein in rat serum. The 71-kDa protein detected in rat serum was also detected in the extracellular medium from primary cultures of rat hepatocytes. Non-denaturing gel electrophoresis with staining for esterase activity showed that a serum carboxylesterase comigrated with the 71-kDa protein. Immunoprecipitation of the 71-kDa enzyme from rat serum decreased esterase activity toward 1-naphthylacetate and para-nitrophenylacetate. The 71-kDa protein immunoprecipitated from rat serum had an N-terminal amino acid sequence identical to that predicted from the cDNA encoding hydrolase S, providing further evidence that hydrolase S is synthesized in and secreted by the liver. The levels of the 67-kDa protein in rat liver microsomes and the levels of the 71-kDa protein in rat serum were co-regulated. Deglycosylation of microsomes and serum converted the 67- and 71-kDa proteins to a 58-kDa peptide, which matches the molecular mass calculated from the cDNA for hydrolase S. These results suggest that the 67-kDa protein in liver microsomes is a precursor form of hydrolase S that undergoes further glycosylation before being secreted into serum. In rats, liver appears to be the only source of hydrolase S because no mRNA encoding hydrolase S could be detected in several extrahepatic tissues. Serum carboxylesterases have been found to play an important role in lipid metabolism and detoxication of organophosphates, therefore, the secretion of hydrolase S and the modulation of its expression by xenobiotics may have physiological as well as toxicological significance.

Animals↗
PubMed1995

Suppression of liver cytochrome P450 by alpha-hederin: relevance to hepatoprotection.

This study was designed to determine the protective effects of alpha-hederin on chemical-induced liver injury in CF-1 mice and to evaluate cytochrome P450 suppression by alpha-hederin as a means of protection. alpha-Hederin pretreatment (30 mumol/kg, sc x 3 days) protected mice from acetaminophen-, bromobenzene-, carbon tetrachloride-, furosemide-, and thioacetamide-induced liver injury, without affecting the hepatotoxicity of chloroform and dimethylnitrosamine. To examine the role of P450 in hepatoprotection by alpha-hederin, liver microsomes were prepared 24 hr following the last dose of alpha-hederin treatment (10 and 30 mumol/kg, sc x 3 days). Treatment of mice with alpha-hederin produced a dose-dependent suppression of liver cytochrome P450 (30-50%) and cytochrome b5 (20-30%) levels, as well as NADPH-cytochrome c reductase activity (15-25%). alpha-Hederin treatment also decreased the activities of P450 enzymes, such as 7-ethoxyresorufin O-dealkylation (65%), 7-pentoxyresorufin O-dealkylation (50%), coumarin 7-hydroxylation (40%), 7-ethoxycoumarin O-deethylation (45%), caffeine N3-demethylation (30-50%), chlorzoxazone 6-hydroxylation (35-55%), and the oxidation of testosterone to 2 alpha-, 6 alpha-, 15 alpha-, 15 beta-, 16 alpha-, 16 beta-, and 18/12 alpha-hydroxyltestosterone, androstenedione, and 6-dehydroxytestosterone (25-60%). Consistent with these observations, the levels of CYP1A, CYP2A, and CYP3A enzymes were also suppressed, as determined by immunoblotting with antibodies against rat P450 enzymes. These results demonstrate that treatment of mice with alpha-hederin decreases the levels and activities of several P450 enzymes. The suppression of P450 appears to be one of mechanisms by which alpha-hederin protects mice from the hepatotoxicity of some chemicals.

Animals↗
PubMed1995

The successful removal of a bleeding intracranial tumour in a severe haemophiliac using an adjusted dose continuous infusion of monoclonal factor VIII.

Ten per cent of patients with haemophilia A develop intracranial haemorrhage (ICH) with a mortality rate of 30% and an incidence of psycho-neurological sequelae in 50% of survivors. ICH may be spontaneous or in association with trauma and other pathology. The generally recommended management is conservative replacement therapy using bolus injections of factor VIII and no neurosurgical intervention. Adjusted dose continuous infusion therapy provides an alternative method of factor VIII administration that is simple, more cost effective and safer through the maintenance of stable plasma VIII:C levels. This method has been successfully used to cover general surgery and the conservative treatment of subarachnoid haemorrhage but is not widely used due to unfamiliarity with the technique. This paper describes the use of continuous infusion of factor VIII concentrates to cover the successful neurosurgical management of a young man with severe haemophilia A who presented with an ICH associated with a bleeding choroid plexus tumour. Surgery was complicated by the development of a factor VIII inhibitor which disappeared following treatment with an immune-tolerance induction programme.

Adolescent↗