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Biomedical subjects

B Murray

Publications and source records attributed to B Murray.

At least 19 recordsLinked to original sources
PubMed2006

The efficacy of amlexanox OraDisc on the prevention of recurrent minor aphthous ulceration.

BACKGROUND: The study was designed to determine the efficacy of OraDisc (active component 2 mg amlexanox) on the prevention of aphthous ulcers treated at the prodromal stage. METHODS: Thermographic imaging was used to confirm the presence of a prodromal ulcer. Fifty-two patients were randomized to receive OraDisc (N = 26) or vehicle patches (N = 26). Patches were applied four times a day for 72 h over the prodromal area. The percentage of subjects who developed an ulcer at 72 h was compared between groups using the Fisher's exact test. RESULTS: About 50% of subjects in the OraDisc group developed an ulcer by day 4 compared with 69% in the vehicle group. Erythema score, ulcer size, pain scores and thermographically active area and temperature all showed trends towards healing in the OraDisc group. CONCLUSION: The OraDisc prevents ulcers from developing when compared with the vehicle patch.

Administration, Topical↗
PubMed2006

Prognostic significance of serial magnetic resonance spectroscopies over the course of radiation therapy for patients with malignant glioma.

BACKGROUND: The standard treatment of high grade gliomas (HGG) involves maximal neuro-surgical debulking, followed by post-operative radiotherapy, with or without concurrent chemotherapy, depending on histologic grade. Despite this aggressive strategy, there are few long-term survivors. Proton magnetic resonance spectroscopy (MRS) is a non-invasive imaging method that can monitor metabolic changes in brain tumours. To date there is little data concerning the prognostic significance of the evolving spectral alterations during a course of radiotherapy. MATERIALS: We report herein a prospective study of patients with HGGs undergoing post-operative radiotherapy. Fourteen consecutively eligible patients with a confirmed histologic diagnosis of malignant glioma and completion of all required MRS imaging were included in this study. All patients had MRS imaging prior to radiotherapy, at week 4 of radiotherapy, and 2 months post-treatment. T1 and T2 weighted images as well as post-gadolinium multi-voxel proton MRS images were obtained. Normalized (tumour metabolite/normal brain metabolite) levels of choline, NAA, creatine, lipid and lactate were calculated. Kaplan-Meier (KM) curves of progression-free and overall survival were constructed based on the evolving patterns of metabolite changes over the course of the images. RESULTS: The mean tumour choline/NAA ratio decreased over the course of therapy, with a reduction observed between the baseline and post-radiotherapy studies (1.91 vs. 1.29, P=0.049). A similar decrease was identified with the mean normalized choline ratio, with a highly significant difference observed between the baseline and post-radiation images (1.61 vs. 0.96, P=0.001). Patients who exhibited more than 40% decrease in normalized choline between the week 4 and post-radiotherapy studies were associated with unfavourable survival (logrank test, P=0.003) and disease progression (logrank test, P=0.012). The Lactate/NAA ratio at the 4th week of radiotherapy and the change in normalized choline/creatine between baseline and week 4 of radiotherapy were also predictive of outcome suggesting the possibility of adaptive, response-based radiation treatment. Patients with two or more poor prognostic MRS indices had a significantly shorter progression-free survival compared with those with zero or one poor indices, with 15% and 68% at 1 year, respectively (logrank test, P=0.045). CONCLUSION: The evolving pattern of spectral changes over the course of radiotherapy, in particular those associated with choline-containing compounds, appears to be prognostic of tumour response and outcome. Based on our data, a decision point may exist in the mid course of radical radiotherapy, at which time consideration of the choline levels could indicate the extent of radiotherapeutic response, thus allowing for individualized treatment modification.

Brain Neoplasms↗
PubMed2005

Clinicopathological features of the tauopathies.

Developments in molecular neuropathology have led to protein-based classification systems for neurodegenerative disorders. Key proteins include alpha-synuclein, amyloid and tau. Alternative mRNA splicing and post-translational change, induced by a bewildering variety of protein modifying processes such as phosphorylation and ubiquitination, have generated insights into new mechanisms of selective neuronal degeneration. The task now is to bring these developments in protein chemistry to the clinic, to try to determine whether this biochemical diversity can help in explaining the phenotypic variability that is so typical of neurodegeneration in general. In this review, we will explore the clinicopathological diversity of the tau-related disorders with specific reference to three of the most common tauopathies, frontotemporal dementia (familial and sporadic), progressive supranuclear palsy and corticobasal degeneration.

Brain↗
PubMed2005

Audit of an inpatient neurology consultation service in a tertiary referral centre: value of the consulting neurologist.

The Mater Misericordiae Hospital is a 575-bed tertiary referral centre with busy medical and surgical subspecialty services (including the national cardiac, cardiothoracic, spinal cord injury and pulmonary hypertension units). An audit of in-patient referrals to a neurology service was carried out over the twelve-month period of January to December 2002 inclusively. Five hundred and seventy seven inpatients were evaluated and managed in conjunction with the referring services. Consultation by the neurological service led to a significant contribution in the management of clinical cases in one of three ways: establishing a de novo diagnosis in patients admitted with active neurological symptoms where no working diagnosis exists (40.7% of referrals), significant alteration in diagnosis where the referring service have already established a specific working diagnosis (11.1% of referrals), or offering advice in the ongoing management of active neurological symptoms when the diagnosis is historically established and secure (48.2% of referrals). In order of frequency the most common reason for referral was stroke (131 cases (22.7%)), seizures unrelated to alcohol (59 cases (10.2%)), alcohol-related neurological problems (55 cases (9.5%)), movement disorders (41 cases (7.1%)), neuromuscular (40 cases (6.9%)), coma (35 cases (6%)), disorders of cognition (31 cases (5.3%)), acute headache (28 case (4.8%)) and functional neurological syndromes (26 cases (4.5%)). This audit highlights the value of a consulting neurology service in a multidisciplinary tertiary referral setting.

Adult↗
PubMed2004

Escalated median dose for pituitary macroadenomas using intensity-modulated radiation therapy.

Three-dimensional conformal radiotherapy (3D CRT) has become an established treatment for pituitary macroadenomas. This study is an investigation into the possible dosimetric advantages of intensity-modulated radiotherapy for such critically located tumors. Three consecutive patients with pituitary macroadenoma previously treated with 3D CRT were replanned with inverse-planned IMRT using Helax-TMS (V.6.0, Helax AB, Uppsala, Sweden. Fusion of computed tomography (CT) with postoperative magnetic resonance imaging (MRI) was performed within the planning system to define the gross tumor volume (GTV), planning target volume (PTV), and normal structures including the optic chiasm. Dose-volume histograms (DVHs) for the 3D CRT plans were then compared with those of the corresponding prospective IMRT plans. Both techniques maintained critical structure doses below tolerance levels while maintaining a minimum dose of 45 Gy to 100% of the PTV. While IMRT plans deliver consistently more heterogeneous dose distributions to the PTV, the median PTV dose is elevated in the IMRT plans compared with the 3D CRT plans. For critically located tumors like these pituitary macroadenomas, IMRT allows escalation of the median dose to the tumor without an accompanying loss in critical structure sparing or creating unacceptable cold spots within the PTV.

Adenoma↗
PubMed2002

Dosimetric verification of inverse planned step and shoot multileaf collimator fields from a commercial treatment planning system.

An inverse treatment planning (ITP) module on a commercial treatment planning system (TPS) (Helax AB, Uppsala, Sweden) is being used for an in-house clinical trial for treatment of nasopharyngeal cancer with contralateral parotid sparing. Intensity modulated radiation therapy (IMRT) fields are delivered by step and shoot multileaf collimator (MLC) with a DMLC enabled Varian 2300 CD (Varian Associates, Palo Alto, CA). A series of testing procedures have been devised to quantify the modeling and delivery accuracy of routine clinical inverse planned IMRT using Helax TMS and the Varian step and shoot MLC delivery option. Testing was done on specific aspects of the TPS modeling germane to DMLC. Measured relative dose factors (head scatter plus phantom scatter) for small MLC fields, normalized to a 10x10 cm2 non-MLC field, were found to differ by 2-3% from the TPS values for the smallest of the fields tested. Relative distributions for small off axis fields were found to be in good agreement. A process for the routine clinical verification of IMRT fields has been implemented. Each IMRT field in an inverse plan is imported into a flat water tank plan and a "beam's eye view" (BEV) dose distribution is generated. This is compared to the corresponding measured BEV dose distribution. The IMRT verification process has also been performed using an anthropomorphic phantom. Large clinical fields (i.e., greater than 14.5 cm in the leaf direction) caused difficulties due to a vendor specific machine restriction, and several techniques for dealing with these were examined. These techniques were (i) the use of static stepping of closed junctions, (ii) the use of two separate IMRT fields for a given gantry angle, and (iii) restricting the overall maximum field size used. The overall process has allowed implementation of an in-house protocol for IMRT use on an initial clinical site. Results of the verification measurements for the first ten patients treated at this center reveal an average maximum dose per IMRT field delivered of 71.0 cGy, with a mean local deviation from the planned dose of -1.2 cGy, and a standard deviation of 2.4 cGy.

Algorithms↗
PubMed2001

An exploration of evolved mental mechanisms for dominant and subordinate behaviour in relation to auditory hallucinations in schizophrenia and critical thoughts in depression.

BACKGROUND: Mental mechanisms have evolved to enable animals (and humans) to be able to function in various social roles. It is suggested that the nature and functions of the mental mechanisms that enable animals to act as a hostile-dominant or threatened-subordinate can be distinguished. It is further suggested these can be internally activated and 'play off' against each other, such that a person 'attacks' themselves and then responds to their own internal attacks with subordinate defences. Hence, a depressed person can submit, feel defeated, belittled, beaten down, or want to run away (escape) from their own self-attacking thoughts, while psychotic voice hearers can feel similarly to their hostile voices. Such internal interactions may relate to depression in both psychotic voice hearers and depressed people. METHOD: A group of 66 voice hearers with a diagnosis of schizophrenia and 50 depressed patients were compared on a series of self-report questionnaires measuring the power of hostile self-directed thoughts/voices and the activation of defensive responses, especially fight/flight. RESULTS: We present evidence that schizophrenic, malevolent voice hearers and self-critical depressed people experience their hostile, internally generated voices/thoughts as powerful, dominating and controlling (i.e. have typical characteristics of a hostile dominant). Moreover, these voices/thoughts activate evolved subordinate defences such as fight/flight and these are associated with depression in both depression and schizophrenia. CONCLUSION: Conceptualizing aspects of depressed and psychotic thinking as relating to evolved mental mechanisms, which are role serving, but can internally play off against each other, may open new ways of investigating certain aspects of severe pathologies.

Adult↗
PubMed2001

A study of metabolites as intermediate effectors in angiogenesis.

Metabolites released from hypoxic tissues have been reported as angiogenic factors in circumstances of reduced tissue oxygenation or an increased rate of metabolism. However, in more recent reports their possible role in angiogenesis prior to the induction of hypoxia-inducible genes appears to have been neglected. In a systematic attempt to evalaute their role, metabolites common to the glycolytic and oxidative pathways (nicotinamide adenine dinucleotide, adenosine diphosphate and adenosine triphosphate), exclusively glycolytic metabolites (pyruvate and lactic acid) and exclusively oxidative metabolites (malate, succinate, fumarate and citrate) were tested to assess their effects upon in vivo angiogenesis and in vitro endothelial cell migration and proliferation. In addition, adenosine was tested due to its proposed role in hypoxia-induced angiogenesis. The angiogenic effects in vivo were examined using the chick chorioallantoic membrane assay and in vitro on chick embryonic capillary endothelial cells using a phagokinetic track/migration assay and crystal violet dye binding/proliferation assay. Metabolites common to the glycolytic and oxidative metabolic pathways and exclusively glycolytic metabolites produced an angiogenic response in vivo and in vitro on endothelial cell proliferation and migration, whereas exclusively oxidative metabolites, with the exception of malate, did not. Adenosine caused an increased proliferation of blood vessels in vivo and stimulated endothelial cell migration and proliferation. Overall, these results implicate metabolites as effectors in angiogenesis and it is proposed that they have a role which is possibly independent of the upregulation of hypoxia-inducible genes.

Adenosine↗
PubMed2001

Ganciclovir pharmacokinetics and cytokine dynamics in renal transplant recipients with cytomegalovirus infection.

Ganciclovir is considered to be the first-line treatment for cytomegalovirus (CMV) in renal transplant recipients. This infection is also associated with elevations of specific plasma cytokines post-transplantation. To investigate daily cytokine response to therapy and ganciclovir pharmacokinetics, 4 transplant recipients (3 males, 1 female) with stable renal allograft function diagnosed with CMV infection were enrolled less than 4 months post-transplant. A creatinine clearance (ClCr) was generated by the Cockroft-Gault (C-G) equation (range: 42.3-68.5 mL/min) to determine ganciclovir dosing. Blood samples were collected for ganciclovir and cytokine [including interleukin (IL)-1beta, IL-2, IL-3, IL-4, IL-6, IL-8, IL-10, TNF-alpha, GM-CSF, and interferon (IFN)-gamma analyses after 7 d of intravenous (i.v.) ganciclovir (dosage range: 165-400 mg daily) therapy and again after 7 d of oral (p.o.) ganciclovir (dosage range: 1000 mg, 2-3 times daily) therapy. Pharmacokinetic ganciclovir was described with a two-compartment model. Total clearance of ganciclovir was consistently greater than ClCr, suggesting tubular secretion. Peak concentrations for i.v. ganciclovir averaged 8.39+/-1.87 microg/mL with minimum concentrations of 0.48+/-0.35 microg/mL. Plasma concentrations were lower but more sustained during a p.o. dosing interval (max=2.12+/-0.58 microg/mL, min=1.15+/-0.34 microg/mL). IL-6, IL-8, IL-10, and TNF-alpha were detectable at multiple times during the study periods while the remainder of the cytokines were only intermittently detectable. Average concentrations (i.v. versus p.o. study period) for TNF-alpha were 40.1+/-17.5 versus 22.1+/-11.2 pg/mL, for IL-8 were 17.1+/-15.6 versus 4.12+/-2.59 pg/mL, and for IL-10 were 7.39+/-5.54 versus 2.64+/-1.06 pg/mL. Concentrations were similar for IL-6 during both studies (9.39+/-5.42 versus 14.7+/-14.8 pg/mL). TNF-alpha, IL-8, and IFN-gamma appeared to correlate with CMV antigenemia. Further investigation of ganciclovir disposition and changes in plasma cytokines in renal transplant recipients during CMV infection may provide insight into variable antiviral responses in renal transplant recipients.

Adult↗
PubMed2000

Evidence that the reactivity of the martian soil is due to superoxide ions.

The Viking Landers were unable to detect evidence of life on Mars but, instead, found a chemically reactive soil capable of decomposing organic molecules. This reactivity was attributed to the presence of one or more as-yet-unidentified inorganic superoxides or peroxides in the martian soil. Using electron paramagnetic resonance spectroscopy, we show that superoxide radical ions (O2-) form directly on Mars-analog mineral surfaces exposed to ultraviolet radiation under a simulated martian atmosphere. These oxygen radicals can explain the reactive nature of the soil and the apparent absence of organic material at the martian surface.

Aluminum Silicates↗
PubMed2000

Deliberate self poisoning with antidepressant drugs: a comparison of the relative hospital costs of cases of overdose of tricyclics with those of selective-serotonin re-uptake inhibitors.

BACKGROUND: Debate continues over the relative merits of tricyclics and selective serotonin re-uptake inhibitors (SSRIs) as first line antidepressant treatment for depression. SSRIs are safer in overdose but more expensive than tricyclics. This report compared the hospital costs of cases of overdose with both groups of drug. METHODS: Records of all persons aged over thirteen years presenting to a general hospital in one year were analysed for demographic information and details of their attendance. RESULTS: There were 1165 episodes of self-poisoning, 151 involving tricyclics as the sole antidepressant and 69 SSRIs as the sole antidepressant. Those taking SSRIs had a shorter (1.96 vs. 2.59 days) and less expensive ( pound330 vs. pound567) stay. A large proportion of this difference in cost was due to a small number of admissions to the Intensive Care Unit. LIMITATIONS: This study used only hospital costs, so excluding costs associated with primary care. CONCLUSIONS AND CLINICAL RELEVANCE: If there were similar cost differences countrywide, the difference in hospital costs of self poisoning with SSRIs and tricyclics would represent an additional pound3.87 million per year due to self poisoning with tricyclics across the whole of England and Wales. This is a small proportion of the estimated pound100 million cost of switching to first-line prescribing of SSRIs for depression.

Adolescent↗
PubMed1999

Lupus anticoagulants form immune complexes with prothrombin and phospholipid that can augment thrombin production in flow.

Lupus anticoagulants (LA) are a family of autoantibodies that are associated with in vitro anticoagulant activity but a strong predisposition to in vivo thrombosis. They are directed against plasma phospholipid binding proteins, including prothrombin. We found that a murine monoclonal antiprothrombin antibody and 7 of 7 LA IgGs tested enhanced binding of prothrombin to 25:75 phosphatidyl serine:phosphatidyl choline vesicles in a concentration-dependent manner. We hypothesized that enhanced binding of prothrombin to phospholipid in the presence of LA IgG might result in increased thrombin production when reactions are performed in flow. Thrombin production by purified prothrombinase components was measured in a phospholipid-coated flow reactor. The flow reactor was incubated with prothrombin, calcium ions, and the IgGs and then perfused with prothrombin, calcium ions, the IgGs, factor Va, and factor Xa. A murine monoclonal antiprothrombin antibody and 4 of 6 LA IgGs from patients with a history of thrombosis increased thrombin production up to 100% over control in the first 15 minutes. In summary, LA IgGs concentrate prothrombin on a phospholipid surface that can augment thrombin production by prothrombinase in flow. These observations suggest that LA might propagate coagulation in flowing blood by facilitating prothrombin interaction with the damaged blood vessel wall.

Animals↗
PubMed1999

Setup reproducibility in radiation therapy for lung cancer: a comparison between T-bar and expanded foam immobilization devices.

PURPOSE: Physiologic and non-physiologic tumor motion complicates the use of tight margins in three-dimensional (3D) conformal radiotherapy. Setup reproducibility is an important non-physiologic cause of tumor motion. The objective of this study is to evaluate and compare patient setup reproducibility using the reusable T-bar and the disposable expanded foam immobilization device (EFID) in radiation therapy for lung cancer. METHODS AND MATERIALS: Two hundred forty-four portal films were taken from 16 prospectively accrued patients treated for lung cancer. Patients were treated with either a pair of anterior and posterior parallel opposing fields (POF), or a combination of POF and a three-field isocentric technique. Each patient was treated in a supine position using either the T-bar setup or EFID. Six patients were treated in both devices over their treatment courses. Field placement analysis was used to evaluate 3D setup reproducibility, by comparing positions of bony landmarks relative to the radiation field edges in digitized simulator and portal images. Anterior-posterior, lateral, and longitudinal displacements, as well as field rotations along coronal and sagittal planes were measured. Statistical analyses of variance were applied to the deviations among portal films of all patients and the subgroup treated with both immobilization methods. RESULTS: For the T-bar immobilization device, standard deviations of the setup reproducibility were 5.1, 3.7, and 5.1 mm in the anterior-posterior, lateral, and longitudinal dimensions, respectively. Rotations in the coronal plane and the sagittal plane were 0.9 degrees and 1.0 degrees, respectively. For the EFID, corresponding standard deviations of set up reproducibility were 3.6 mm, 5.3 mm, 5.4 mm, 0.7 degrees and 1.4 degrees, respectively. There was no statistically significant difference (p = 0.22) in the 3D setup reproducibility between T-bar and EFID. Subgroup analysis for the patients who were treated with both immobilization devices did not reveal a difference either. There was no consistent systematic error from simulator to treatment unit identified for either immobilization device. CONCLUSION: Although the optimal immobilization technique and patient positioning for thoracic radiotherapy have yet to be determined, this study indicates that T-bar is comparable with EFID in its setup reproducibility. In view of the inherent advantages of T-bar, it has become a standard immobilization device at our institution. The observed range of displacements in field positioning with either immobilization device implies that one cm (two standard deviations [SD] of setup error) will be a more appropriate margin to allow for setup variability in radiation therapy for lung cancer.

Equipment Design↗
PubMed1999

Direct measurement of recombination frequency in interspecific hybrids between Hordeum vulgare and H. bulbosum using genomic in situ hybridization.

Two different genotypes of diploid Hordeum vulgare x H. bulbosum hybrids, which differ in their pattern of meiotic metaphase pairing behaviour, were investigated at MI and AI by genomic in situ hybridization (GISH). One hybrid, 102C2, showed a high frequency of bivalents at metaphase I whereas the other, 103K5, showed a high frequency of univalents. The GISH analysis of both hybrids established that pairing occurred only between chromosomes of different parental genomes and revealed that pairing frequency greatly exceeded recombination. Hybrid 102C2 had a significantly higher recombination frequency than 103K5, but in both hybrids recombination involved only distal chromosome regions. However, an interesting finding is that the ratio of recombination to pairing frequency in 103K5 (1:8.9) is twice as high compared with 102C2 (1:17). The hybrids also differed in chromosome stability; little chromosome elimination occurred in 102C2 but 103K5 showed extensive chromosome loss. It appears that the high frequency of bound arms at MI favours retention of H. bulbosum chromosomes and maintains stability of chromosome numbers in PMCs. Various ideas are put forward to explain the discrepancy between meiotic pairing frequency and recombination in these hybrids.

Hordeum↗