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Biomedical subjects

M J Peters

Publications and source records attributed to M J Peters.

At least 19 recordsLinked to original sources
PubMed1996

Computation of neuromagnetic fields using finite-element method and Biot-Savart law.

The finite-element method in combination with the Biot-Savart law is described to compute the magnetic field distribution generated by a dipolar source within a homogeneous volume conductor of an arbitrary shape. In order to calculate the three independent components of the magnetic field outside the volume conductor by means of the Biot-Savart law, the distribution of the current throughout the medium is required. A finite-element mesh is constructed using four-node tetrahedral elements. The potential in each node is computed numerically by the finite-element method using the proper continuity conditions across the boundaries. The gradient of the potential denotes the current density within an element. The components of the magnetic induction are calculated by numerical integration, applying the current density within the tetrahedrons. Simulations are carried out to assess the numerical accuracy for a homogeneous spherical volume conductor. Errors of 3% can be obtained with a locally refined spherical mesh containing about 1000 nodes, for dipoles at any depth and any orientation. A homogeneous realistically shaped model with the shape of the inside of the skull is obtained from magnetic resonance images.

Biomedical Engineering↗
PubMed1995

Beta-adrenoceptor agonists interfere with glucocorticoid receptor DNA binding in rat lung.

Inhaled beta 2-adrenoceptor agonists are the most effective bronchodilator treatment in asthma, yet paradoxically high doses may be associated with increased asthma morbidity and mortality. Steroids are the most effective therapy in controlling asthmatic inflammation and act by binding to specific sequences of DNA (GRE), thus modulating gene transcription. We report that in rat lung, the beta 2-adrenoceptor agonists, salbutamol and fenoterol, decrease the binding of glucocorticoid receptors to GRE, by 46 +/- 4% although it has no effect on the affinity or number of glucocorticoid receptors. The inhibition of GRE binding by salbutamol is concentration-dependent, can be blocked by propranolol and is seen following forskolin treatment. This effect appears to be due to an interaction between the glucocorticoid receptor and the transcription factor, cAMP response element binding protein (CREB), which is activated by high concentrations of beta 2-adrenoceptor agonists. We suggest that by this mechanism high doses of inhaled beta 2-adrenoceptor agonists may inhibit the anti-inflammatory effects of endogenous glucocorticoids and exogenous corticosteroids used for asthma therapy.

Albuterol↗
PubMed1995

Differences in binding of glucocorticoid receptor to DNA in steroid-resistant asthma.

Although glucocorticosteroids are a very effective treatment for asthma and other chronic inflammatory diseases, a small proportion of patients are resistant to their therapeutic effects. The molecular mechanism for this steroid resistance is unclear. Steroid resistance cannot be explained by pharmacokinetic mechanisms, by a defect in the binding of steroids to glucocorticoid receptors, nor by defective nuclear translocation of this receptor, thereby suggesting that the molecular abnormality lies distal to nuclear translocation. We examined the ability of nuclear translocated glucocorticoid receptors to bind to their DNA binding sites (GRE) using electrophoretic mobility shift assays in PBMC from patients with steroid-sensitive and steroid-resistant asthma. The binding of the glucocorticoid receptor to DNA in these patients was also studied using Scatchard analysis. Dexamethasone induced a significant rapid and sustained twofold increase in GRE binding in PBMCs from steroid-sensitive asthmatic patients and nonasthmatic individuals, but this was markedly reduced in steroid-resistant asthmatic patients. Scatchard analysis of glucocorticoid receptor-GRE binding showed no change in binding affinity but did show a reduced number of receptors available for DNA binding in the steroid-resistant patients. These results suggest that the ability of the glucocorticoid receptor to bind to GRE is impaired in steroid-resistant patients because of a reduced number of receptors available for binding to DNA.

Adult↗
PubMed1995

Individually shaped volume conductor models of the head in EEG source localisation.

Inverse solution techniques based on electroencephalograph (EEG) measurements have become a powerful means of gaining knowledge about the functioning of the brain. A model of the head and a potential computation method are necessary to describe the EEG problem mathematically. The generation of realistically shaped three-compartment models of the head is discussed. The isolated problem approach for the boundary element method is applied to develop a fast and accurate numerical solution of the EEG forward problem. Accuracy studies with this approach show that dipole positions can be reconstructed within a distance of 3 mm from the original positions. Inverse simulations indicate that the incorporation of the individual head shape may significantly influence the reconstructed dipole position but not its magnitude and orientation, in comparison with the commonly used three-sphere model. However, the presence of noise in the simulated potential data affects the solutions based on realistically shaped models more than those of the simple three-sphere model. The increased sensitivity of the former models to noise in the data remains a serious drawback for their practical application to EEG source localisations.

Electroencephalography↗
PubMed1995

Cytomegalovirus retinitis in AIDS.

Cytomegalovirus retinitis is common in adults with AIDS but has been reported infrequently in children with perinatally acquired HIV infection. The cases are presented of two infants with vertically acquired HIV infection who developed disseminated cytomegalovirus infection and retinitis, and who posed difficult management issues.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Effects of glucocorticoids on transcription factor activation in human peripheral blood mononuclear cells.

Glucocorticoids have an inhibitory effect on inflammatory and immune responses, and this may be through the modulation of transcription factor binding to DNA. The interaction of the transcription factors, activator protein-1 (AP-1), nuclear factor kappa B (NF kappa B), and cAMP-responsive element binding protein (CREB) with DNA and glucocorticoid receptors (GR) was analyzed in human peripheral blood mononuclear cells by gel mobility shift assays. TNF-alpha, IL-1 beta and phorbol myristate acetate (PMA) treatment increased AP-1 and NF kappa B DNA binding by up to 200% but decreased CREB binding (38%) over a 60-min time course. Dexamethasone produced a rapid and sustained increase in glucocorticoid response element binding and a concomitant 40-50% decrease in AP-1, NF kappa B, and CREB DNA binding that was blocked by combined dexamethasone and cytokine or PMA treatment. These latter effects were due to increases in the nuclear localization of GR, not to reduced amounts of the other transcription factors. This suggests that in these cells GR within the nucleus interacts with cytokine-stimulated transcription factors by the process of cross coupling. This may be an important molecular site of steroid action.

Base Sequence↗
PubMed1995

Reduced dose salbutamol in comparison with standard dosage for symptom relief in asthma.

Regular treatment with beta 2-agonists has been reported to be associated with an increase in risk of asthma death or near death, and with a deterioration in asthma symptom control. Low-dose beta 2-agonists provide effective bronchodilatation and bronchoprotection, even though maximal bronchodilatation is not achieved, and they may offer a better safety profile. In a double-blind, randomized,, cross-over study, we evaluated the efficacy of low-dose salbutamol metered-dose inhaler (50 micrograms.puff-1), used over a period of 2 weeks, compared with a standard dose (100 micrograms.puff-1) in control of asthma symptoms in 20 moderately severe asthmatic subjects using inhaled glucocorticosteroid therapy. Asthma control was assessed by symptom scores, peak flow rates, spirometry, inhaler usage and, where possible, by bronchial responsiveness to methacholine. Despite a 46% reduction in mean weekly salbutamol dosage, mean forced expiratory volume in one second (FEV1), morning and evening peak expiratory flow (PEF), PEF variability, dose of methacholine provoking a 20% decrease in FEV1 (PC20) (n=9), and symptom scores showed no difference between low-dose and standard inhaler treatment periods. Low-dose inhaler administration resulted in a small but significant increase in number of inhaler actuations. Low-dose salbutamol metered-dose inhaler may, thus, be useful for control of symptoms in moderately severe asthma. This strategy could be used to achieve a reduction in total beta 2-agonist usage, which may minimize any potential for adverse effects.

Administration, Inhalation↗
PubMed1994

The effects of glucocorticoids on phorbol ester and cytokine stimulated transcription factor activation in human lung.

Glucocorticoids have a wide variety of effects which result in the dampening of inflammatory and immune responses and other challenges to homeostasis. An important site of steroid action may be on the control of transcription factor binding to DNA. The interaction of the transcription factors, activator protein 1 (AP-1) and nuclear factor kappa from B cells (NF kappa B) with DNA and glucocorticoid receptors was analysed by gel mobility shift assays following stimulation by tumour necrosis factor alpha (TNF alpha) and a phorbol ester (PMA) that activates protein kinase C. PMA and TNF alpha both caused significant (180-340%) increases in AP-1 and NF kappa B DNA binding which peaked at 15 minutes and decreased to a constant elevated level at between 1-3 hrs and was sustained for 24hrs. Dexamethasone (1 microM) caused a rapid and long lasting 40-50% decrease in both AP-1 and NF kappa B DNA binding lasting over 24hrs. Combined treatment with dexamethasone and PMA or TNF alpha prevented the increase in both AP-1 and NF kappa B binding due to PMA and TNF alpha returning levels to those seen in control untreated samples. This suggests that in human lung, the glucocorticoid receptor functionally interacts within the nucleus with other transcription factors that are induced by inflammatory mediators such as cytokines. This may be an important molecular site of steroid action in chronic inflammatory lung diseases such as asthma.

Adolescent↗
PubMed1994

Rifampicin in pneumococcal meningoencephalitis.

The cases are reported of two infants with pneumococcal meningitis in whom initial antibiotic treatment was ineffective despite the organisms being sensitive to the drugs used. A clinical and radiological diagnosis of meningoencephalitis was made. A rapid improvement followed the addition of rifampicin treatment.

Anti-Bacterial Agents↗
PubMed1993

Topography and source analysis of brain activity associated with selective spatial attention and memory search.

We investigated the topographical aspects of the ERP reflections of visual spatial attention and memory search. Spatial attention was found to enhance the amplitudes of the P1 and N1 deflections. The brain activity in the P1-N1 latency range could be modeled with a single moving equivalent dipole, or alternatively with two stationary dipoles in a spatio-temporal dipole model. The dipoles were located in mesial and lateral posterior brain regions. Similar dipole solutions were obtained for ERPs to attended and unattended stimuli. Increasing the memory search requirements of the task resulted in an increase of late negativity, which was topographically distinguishable from the P3 component.

Attention↗
PubMed1993

Processing MRI data for electromagnetic source imaging.

Estimation of the source of activity in the brain from electro- and magneto-encephalographic measurements is becoming increasingly common. Structural information could assist in improving the calculation of the sources as well as providing the context of the source location. Magnetic resonance images are very useful for this purpose, but they still need to undergo various processing steps. The paper describes in detail a practical method for full automatic processing of MRI images of a head, including segmentation of the images and triangulation of the surfaces.

Brain↗
PubMed1993

A comparison of different numerical methods for solving the forward problem in EEG and MEG.

In view of the complexity of the conductivity and the geometry of the human head, a numerical method would appear to be necessary for the adequate calculation of the electric potential and the magnetic induction generated by electric sources within the brain. Four numerical methods that could be used for solving this problem are the finite-difference method, the finite-element method, the boundary-element method, and the finite-volume method. These methods could be used to calculate the electric potential and the magnetic induction directly. Alternatively, they could be applied to the electric potential or the electric field and the magnetic induction could then be determined by numerical integration of the Biot-Savart law. In this paper the four numerical methods are briefly reviewed. Thereafter the relative merits of the methods and the various options for using them to solve the EEG and MEG problem are evaluated.

Brain Mapping↗