Search PubMed⌕ Search

Biomedical subjects

J Brown

Publications and source records attributed to J Brown.

At least 37 records · Page 2Linked to original sources
PubMed2005

The EXPURT model for calculating external gamma doses from deposited material in inhabited areas.

EXPURT, NRPB's model for calculating external gamma doses in inhabited areas, was originally developed in the mid-1980s. Deposition on surfaces in the area, the subsequent transfer of material between different surfaces or its removal from the system, and dose rates in various locations from material on the different surfaces are modelled. The model has been updated to take account of more recent experimental data on the transfer rates between surfaces and to make it more flexible for use in assessing dose rates following an accidental release. EXPURT is a compartmental model and models the transfer of material between the surfaces using a set of first order differential equations. It enables the impact of the decontamination of surfaces on doses and dose rates to be explored. The paper describes the EXPURT model and presents some preliminary results obtained using it.

Air Pollutants, Radioactive↗
PubMed2005

Plasma level-dependent effects of methylphenidate on task-related functional magnetic resonance imaging signal changes.

RATIONALE: Methylphenidate (MPH) is a dopamine and noradrenaline enhancing drug used to treat attentional deficits. Understanding of its cognition-enhancing effects and the neurobiological mechanisms involved, especially in elderly people, is currently incomplete. OBJECTIVES: The aim of this study was to investigate the relationship between MPH plasma levels and brain activation during visuospatial attention and movement preparation. METHODS: Twelve healthy elderly volunteers were scanned twice using functional magnetic resonance imaging (fMRI) after oral administration of MPH 20 mg or placebo in a within-subject design. The cognitive paradigm was a four-choice reaction time task presented at two levels of difficulty (with and without spatial cue). Plasma MPH levels were measured at six time points between 30 and 205 min after dosing. FMRI data were analysed using a linear model to estimate physiological response to the task and nonparametric permutation tests for inference. RESULTS: Lateral premotor and medial posterior parietal cortical activation was increased by MPH, on average, over both levels of task difficulty. There was considerable intersubject variability in the pharmacokinetics of MPH. Greater area under the plasma concentration-time curve was positively correlated with strength of activation in motor and premotor cortex, temporoparietal cortex and caudate nucleus during the difficult version of the task. CONCLUSION: This is the first pharmacokinetic/pharmacodynamic study to find an association between plasma levels of MPH and its modulatory effects on brain activation measured using fMRI. The results suggest that catecholaminergic mechanisms may be important in brain adaptivity to task difficulty and in task-specific recruitment of spatial attention systems.

Aged↗
PubMed2005

Assessment of quality of life in the supportive care setting of the big lung trial in non-small-cell lung cancer.

PURPOSE: The Big Lung Trial (BLT) was a large, pragmatic trial to evaluate the addition of chemotherapy to primary treatment (ie, surgery, radical radiotherapy, or supportive care) in non-small-cell lung cancer (NSCLC). In the supportive care group, there was a small but significant survival benefit in patients treated with chemotherapy compared with supportive care alone (no chemotherapy). A substudy was undertaken to evaluate the quality of life (QoL) implications of the treatment options. QoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires C30 (QLQ-C30) and LC17, and daily diary cards. PATIENTS AND METHODS: EORTC QLQ-C30 and LC17 were collected at 0, 6 to 8, 12, 18, and 24 weeks. Diary cards were completed during the first 12 weeks of the study. The primary end point was global QoL at 12 weeks. RESULTS: A total of 273 patients were randomly assigned: 138 to no chemotherapy and 135 to chemotherapy. There was no evidence of a large detrimental effect on QoL of chemotherapy. No statistically significant differences in global QoL or physical/emotional functioning, fatigue and dyspnea, and pain were detected at 12 weeks. Higher rates of palliative radiotherapy in the no chemotherapy arm may have lessened differences in QoL. Global QoL, role functioning, fatigue, appetite loss, and constipation were prognostic indicators of survival at 12 weeks. CONCLUSION: There were no important adverse effects of chemotherapy on QoL.

Aged↗
PubMed2005

Requirements of future models for inhabited areas.

Models for inhabited areas are used in a variety of applications for accidental or continuous releases of radioactivity to atmosphere. Pathways of interest are external exposure from radioactive material in the cloud or deposited on indoor and outdoor surfaces and people, inhalation from the plume and from material resuspended from the ground. In developing a model for inhabited areas it is necessary to consider what the end users may need and ensure that the model is appropriate for the application; different levels of detail may be appropriate for different applications. This paper considers the main processes governing exposure in inhabited areas, commenting on the extent to which we understand them and how well current models reflect this understanding. It also identifies where the authors believe future modelling is needed and the key areas where the current inhabited area models could be improved.

Air Pollution, Indoor↗
PubMed2005

Developmental Vitamin D3 deficiency alters the adult rat brain.

There is growing evidence that Vitamin D(3) (1,25-dihydroxyvitamin D(3)) is involved in brain development. We have recently shown that the brains of newborn rats from Vitamin D(3) deficient dams were larger than controls, had increased cell proliferation, larger lateral ventricles, and reduced cortical thickness. Brains from these animals also had reduced expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor. The aim of the current study was to examine if there were any permanent outcomes into adulthood when the offspring of Vitamin D(3) deficient dams were restored to a normal diet. The brains of adult rats were examined at 10 weeks of age after Vitamin D(3) deficiency until birth or weaning. Compared to controls animals that were exposed to transient early Vitamin D(3) deficiency had larger lateral ventricles, reduced NGF protein content, and reduced expression of a number genes involved in neuronal structure, i.e. neurofilament or MAP-2 or neurotransmission, i.e. GABA-A(alpha4). We conclude that transient early life hypovitaminosis D(3) not only disrupts brain development but leads to persistent changes in the adult brain. In light of the high incidence of hypovitaminosis D(3) in women of child-bearing age, the public health implications of these findings warrant attention.

Aging↗
PubMed2005

A randomised study of whole-breast vs tumour-bed irradiation after local excision and axillary dissection for early breast cancer.

AIMS: Whole-breast radiotherapy (WBRT) after conservative surgery for early breast cancer is a routine standard of care. Despite this, a number of uncertainties in management still exist. Over recent years, a number of new technologies have allowed the development of partial-breast irradiation, with the intention of improving the risk-benefit relationship of routine breast radiotherapy. We report the results of a trial comparing partial- with WBRT, with prolonged follow-up. MATERIALS AND METHODS: Between 1986 and 1990, 174 women were randomised to receive conventional whole-breast radiotherapy (WBRT) (40 Gy in 15 fractions), with a tumour-bed boost or partial-breast irradiation by a variety of techniques. Recruitment was problematic, and the trial closed prematurely well before meeting its recruitment target. RESULTS: A trend was observed towards higher local recurrence and a higher locoregional recurrence rate after irradiation of the tumour bed alone. Distant recurrence and survival were the same. CONCLUSIONS: Conclusions are limited in view of the failure to complete accrual of the target of 400 participants, and in the context of the techniques of partial-breast radiotherapy used during this study, which would not compare with those in current use. Tumour-bed irradiation alone cannot currently be recommended as routine treatment outside the context of clinical trial.

Adult↗
PubMed2005

A new guide to mandibular resection for oral squamous cell carcinoma based on the Cawood and Howell classification of the mandible.

A new guide for mandibular resection in the management of oral squamous cell carcinoma based on the Cawood and Howell classification of the jaws is suggested. This was a retrospective review of case records and pre-operative orthopantomograms (OPG), bone scintigraphy and magnetic resonance imaging (MRI). The classification of the mandible was based on the residual bone height as measured in the molar region of the OPG to be equivalent to the Cawood and Howell classification of the mandible (Class I-II dentate or immediate post-extraction), Class III-IV >20mm well-rounded or knife-edge ridge, and Class V-VI <20mm (flat or depressed ridge form). Of the 77 patients, 58% (22/38) of Class I-II, 43% (9/23) of Class III-IV and 6% (1/16) of Class V-VI were treated with a marginal (rim) resection of the mandible. The predictability of the pre-operative investigations was more accurate in the edentulous mandible (Class III-VI). A simple guide is suggested for mandibular resection taking into account the pre-operative investigations, the estimation of invasion clinically, and the Cawood and Howell classification of ridge resorption.

Adult↗
PubMed2005

Empowering primary care to tackle the obesity epidemic: the Counterweight Programme.

OBJECTIVE: To improve the management of obese adults (18-75 y) in primary care. DESIGN: Cohort study. SETTINGS: UK primary care. SUBJECTS: Obese patients (body mass index > or =30 kg/m(2)) or BMI> or =28 kg/m(2) with obesity-related comorbidities in 80 general practices. INTERVENTION: The model consists of four phases: (1) audit and project development, (2) practice training and support, (3) nurse-led patient intervention, and (4) evaluation. The intervention programme used evidence-based pathways, which included strategies to empower clinicians and patients. Weight Management Advisers who are specialist obesity dietitians facilitated programme implementation. MAIN OUTCOME MEASURES: Proportion of practices trained and recruiting patients, and weight change at 12 months. RESULTS: By March 2004, 58 of the 62 (93.5%) intervention practices had been trained, 47 (75.8%) practices were active in implementing the model and 1549 patients had been recruited. At 12 months, 33% of patients achieved a clinically meaningful weight loss of 5% or more. A total of 49% of patients were classed as 'completers' in that they attended the requisite number of appointments in 3, 6 and 12 months. 'Completers' achieved more successful weight loss with 40% achieving a weight loss of 5% or more at 12 months. CONCLUSION: The Counterweight programme provides a promising model to improve the management of obesity in primary care.

Adolescent↗
PubMed2005

Anticancer activities of pomegranate extracts and genistein in human breast cancer cells.

Previous studies have demonstrated the anticarcinogenic activity of pomegranate extracts and genistein in a series of human cancer cells. In the present study, the potential anticancer effects of pomegranate extracts and genistein on inhibition of cell proliferation and induction of apoptosis in human breast cancer cells was investigated. Human breast cancer cells (MCF-7) were cultured as monolayers in complete RPMI 1640 medium. The cells were cultured for 48 hours to allow growth and achieve about 80% confluence in 48-well culture plates, and then exposed to the agents for 24 hours in single and combination treatments. Post-treatment growth rate and apoptosis induction were assessed by the use of a series of bioassays-lactate dehydrogenase and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (inner salt) for viability and cytotoxicity; acridine orange-ethidium bromide and terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling assays for induction of apoptosis. Both pomegranate extracts and genistein had significant (dose- and time-dependent) cytotoxic and growth inhibition effects on MCF-7 cancer cells. Both growth inhibition and cytotoxicity were significantly higher (P < .01) in the combination treatments than in the single treatments with either agent. The data revealed that both drugs in single and in combination treatments induced apoptosis in MCF-7 cells. Apoptotic induction in the combination treatments was significantly higher (P < .01) than in single treatments. Both pomegranate extracts and genistein inhibit the growth of MCF-7 breast cancer cells through induction of apoptosis, with combination treatment being more efficacious than single treatments.

Antineoplastic Agents↗
PubMed2005

The inhibition of neutrophil-endothelial cell adhesion by hyaluronan independent of CD44.

OBJECTIVE: To study the effect of hyaluronan on cell adhesion and recruitment both in vitro and in vivo, since hyaluronan both inhibits restenosis and is anti-inflammatory. When administered to animals undergoing angioplasty the recruitment of cells into the restenotic plaque is inhibited, as well as into inflammatory lesions. The recent discovery that ICAM-1 binds hyaluronan and exhibits the B(X(7))B HA binding motif, led us also to investigate whether cell adhesion could be modulated by hyaluronan. MATERIALS AND METHODS: Human neutrophils were adhered to human umbilical vein (HUVEC) or Ea.hy.926 HUVEC cells stimulated with phorbol myristate acetate (PMA) or tumour necrosis factor (TNFalpha). Neutrophil binding in vivo utilized FMLP-stimulated hamster cheek pouch post-capillary venules. RESULTS: Hyaluronan inhibited human neutrophil adhesion to both PMA and TNFalpha-stimulated HUVEC. Ea.hy.926 human immortal HUVECs expressed ICAM-1 in response to TNFalpha and PMA. E-selectin was also upregulated by 6 h with TNFalpha but not significantly with PMA. TNFalpha induced CD44 expression within 4 h, but PMA not significantly up to 6 h. However, specific binding of [125I]hyaluronan to Ea.hy.926 cells was increased by PMA-stimulation at 4 h. Neutrophil adhesion to PMA-stimulated Ea.hy.926 HUVECs was inhibited in a concentration dependent fashion by both anti-ICAM-1 and hyaluronan (1 ng/ml-10 microg/ml) at 4 h. At 1 mg/ml adhesion was stimulated by hyaluronan. Hyaluronan had no effect on neutrophil adhesion to resting Ea.hy.926 cells. Hyaluronan (25 mg/kg, i.v.) inhibited cell adhesion to FMLP-stimulated post capillary venules of the hamster cheek pouch, whilst leaving cell rolling unaffected. CONCLUSIONS: These results show that hyaluronan, at concentrations below those where intra-molecular associations occur, binds selectively to stimulated endothelial cells and inhibits neutrophil adhesion in vitro and in vivo via a mechanism which may involve molecules other than CD44, such as ICAM-1.

Animals↗
PubMed2005

Newborn screening for congenital heart defects: a systematic review and cost-effectiveness analysis.

OBJECTIVES: To provide evidence to inform policy decisions about the most appropriate newborn screening strategy for congenital heart defects, identifying priorities for future research that might reduce important uncertainties in the evidence base for such decisions. DATA SOURCES: Electronic databases. Groups of parents and health professionals. REVIEW METHODS: A systematic review of the published medical literature concerning outcomes for children with congenital heart defects was carried out. A decision analytic model was developed to assess the cost-effectiveness of alternative screening strategies for congenital heart defects relevant to the UK. A further study was then carried out using a self-administered anonymous questionnaire to explore the perspectives of parents and health professionals towards the quality of life of children with congenital heart defects. The findings from a structured review of the medical literature regarding parental experiences were linked with those from a focus group of parents of children with congenital heart defects. RESULTS: Current newborn screening policy comprises a clinical examination at birth and 6 weeks, with specific cardiac investigations for specified high-risk children. Routine data are lacking, but under half of affected babies, not previously identified antenatally or because of symptoms, are identified by current newborn screening. There is evidence that screen-positive infants do not receive timely management. Pulse oximetry and echocardiography, in addition to clinical examination, are alternative newborn screening strategies but their cost-effectiveness has not been adequately evaluated in a UK setting. In a population of 100,000 live-born infants, the model predicts 121 infants with life-threatening congenital heart defects undiagnosed at screening, of whom 82 (68%) and 83 (69%) are detected by pulse oximetry and screening echocardiography, respectively, but only 39 (32%) by clinical examination alone. Of these, 71, 71 and 34, respectively, receive a timely diagnosis. The model predicts 46 (0.5%) false-positive screening diagnoses per 100,000 infants with clinical examination, 1168 (1.3%) with pulse oximetry and 4857 (5.4%) with screening echocardiography. The latter includes infants with clinically non-significant defects. Total programme costs are predicted of pound 300,000 for clinical examination, pound 480,000 for pulse oximetry and pound 3.54 million for screening echocardiography. The additional cost per additional timely diagnosis of life-threatening congenital heart defects ranges from pound 4900 for pulse oximetry to pound 4.5 million for screening echocardiography. Including clinically significant congenital heart defects gives an additional cost per additional diagnosis of pound 1500 for pulse oximetry and pound 36,000 for screening echocardiography. Key determinants for cost-effectiveness are detection rates for pulse oximetry and screening echocardiography. Parents and health professionals place similar values on the quality of life outcomes of children with congenital heart defects and both are more averse to neurological than to cardiac disability. Adverse psychosocial effects for parents are focused around poor management and/or false test results. CONCLUSIONS: Early detection through newborn screening potentially can improve the outcome of congenital heart defects; however the current programme performs poorly, and lacks monitoring of quality assurance, performance management and longer term outcomes. Pulse oximetry is a promising alternative newborn screening strategy but further evaluation is needed to obtain more precise estimates of test performance and to inform optimal timing, diagnostic and management strategies. Although screening echocardiography is associated with the highest detection rate, it is the most costly strategy and has a 5% false-positive rate. Improving antenatal detection of congenital heart defects increases the cost per timely postnatal diagnosis afforded by any newborn screening strategy but does not alter the relative effects of the strategies. An improvement of timely management of screen positive infants is essential. Further research is required to refine the detection rate and other aspects of pulse oximetry, to evaluate antenatal screening strategies more directly, and to investigate the psychosocial effects of newborn screening for congenital heart defects.

Adolescent↗
PubMed2004

Pulmonary metastasectomy for pediatric solid tumors.

Most pediatric thoracic malignancy is pulmonary disease secondary to solid tumors of childhood. The management of isolated pulmonary metastases in adulthood is well documented. Little has been published to document the long-term outcome of pulmonary metastasectomy in childhood. A retrospective study was undertaken to assess the results of surgery for isolated pulmonary metastases. Twenty children underwent surgery over 12 years (mean follow-up 8 years). Five had Wilms' tumor (mean age 51 months), eight had osteogenic sarcoma (mean age 141 months), three had rhabdomyosarcoma (mean age 92 months), two had hepatoblastoma (mean age 30 months) and two had teratoma (mean age 72 months). Four had bilateral synchronous metastases and thoracotomies, and one had bilateral metachronous metastases and thoracotomies. Nineteen children were discharged well within 10 days of surgery. There was one early complication: a death due to pneumonia. Four children subsequently died postoperatively with cranial metastases (mean 29 months postoperatively). The remaining 16 children remain alive and well. As part of the combined therapy, these results would support an aggressive surgical approach to this disease. Preoperative assessment should include contrast enhanced computed tomogram of the head and chest as well as chest X-ray taken immediately preoperatively to exclude metastases. Bilateral synchronous and metachronous thoracotomy is well tolerated in childhood.

Child↗
PubMed2004

Potent activation of multiple signalling pathways by C-peptide in opossum kidney proximal tubular cells.

AIMS/HYPOTHESIS: Proinsulin C-peptide is generally believed to be inert without any appreciable biological functions. However, it has been shown to modulate a variety of cellular processes important in the pathophysiology of diabetic complications. We therefore investigated the ability of C-peptide to stimulate intracellular signalling pathways in kidney proximal tubular cells, the altered activation of which may possibly be related to the development of diabetic nephropathy. METHODS: Extracellular signal-regulated kinase (ERK) and Akt phosphorylation were evaluated by western blotting. ERK activity was measured by in vitro kinase assay. Intracellular Ca(2+) was evaluated by confocal imaging. The membrane and cytosol-associated fractions of protein kinase C (PKC) isoforms were evaluated by western blotting. Proliferation was assessed by thymidine incorporation assay. RESULTS: Using the opossum proximal tubular kidney cell line as a model, we demonstrated that at high picomolar to low nanomolar concentrations, C-peptide stimulates extracellular signal-regulated mitogen-activated kinase (3.3+/-0.1-fold over basal at 3 minutes) and phosphatidylinositol 3-kinase (4.1+/-0.05-fold over basal at 5 minutes). ERK activation was attenuated by pre-treatment with a PKC inhibitor and abolished by pertussis toxin. Elevations of intracellular [Ca(2+)] are seen in response to 5 nmol/l C-peptide with consequent activation of PKC-alpha. Pre-treatment with pertussis toxin abolished PKC-alpha. C-peptide is also a functional mitogen in this cell type, stimulating significantly increased cell proliferation. Proliferation was attenuated by wortmannin and pertussis toxin pre-treatments. None of these effects is reproduced by scrambled C-peptide. CONCLUSIONS/INTERPRETATION: This study provides evidence that C-peptide, within physiological concentration ranges, stimulates many signalling pathways in opossum kidney cells.

Androstadienes↗