Showing papers by "Guy's and St Thomas' NHS Foundation Trust published in 1995"

Correlations between changes in disability and T2‐weighted brain MRI activity in multiple sclerosis: A follow‐up study

Abstract: Article abstract—We obtained two conventional unenhanced T2-weighted brain MRI scans, separated by an interval of 24 to 36 months, in 281 patients with multiple sclerosis (MS). At the time of each scan, clinical disability was rated using the Kurtzke Expanded Disability Status Scale (EDSS). Changes in disability between the two examinations correlated weakly but significantly with the number of new (Spearman9s rank correlation coefficient = 0.13; p = 0.02) and enlarging (Spearman9s rank correlation coefficient = 0.18; p = 0.002) MRI lesions. This result suggests that brain T2--weighted MRI is a useful supplementary marker of disease activity in definitive (phase 111) clinical treatment trials in MS.

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

Abstract: 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.

Epitope specificity of monoclonal anti-beta 2-glycoprotein I antibodies derived from patients with the antiphospholipid syndrome.

Abstract: beta 2-Glycoprotein I (beta 2GPI) has been identified as a cofactor in the recognition of the phospholipid Ag cardiolipin (CL) by anticardiolipin Ab (aCL) purified from patients with autoimmune diseases. However, there is considerable controversy as to the exact nature of the epitopes to which these Abs are directed. mAb derived from patients with the antiphospholipid syndrome bound to CL only in the presence of beta 2GPI. Synthetic peptides that span the fifth C-terminal domain of beta 2GPI supported the binding of one of the mAbs to CL in a beta 2GPI-free system. These peptides possessed the phospholipid binding sequence Cys281-Lys-Asn-Lys-Glu-Lys-Lys-Cys288. Three of the mAbs bound to beta 2GPI that had been adsorbed on gamma-irradiated microtiter plates. Binding to beta 2GPI was inhibited in a dose-dependent manner by the peptides from the carboxyl-terminal end of beta 2GPI and soluble beta 2GPI, indicating that the mAb bound to peptides and beta 2GPI in free solution. Thus, mAbs derived from patients with the antiphospholipid syndrome have specificity for epitopes on the fifth domain of beta 2GPI. Our results support the idea that beta 2GPI acts as a primary Ag for these Abs.

Survival after fetal aortic balloon valvoplasty

Abstract: The pre- and postnatal course of a child surviving after successful intrauterine balloon aortic valvoplasty for critical aortic stenosis is described. She is now well at 4 years of age. A clearer understanding of the hemodynamics in such cases and improved catheter technology are necessary before this is advocated as a generally applicable technique. However, the outcome in this case is promising for the future of fetal interventional procedures.

Cystic fibrosis mutation analysis: Report from 22 U.K. regional genetics laboratories

Abstract: We have collated the results of cystic fibrosis (CF) mutation analysis conducted in 22 laboratories in the United Kingdom. A total of 9,807 CF chromosomes have been analysed, demonstrating 56 different mutations so far observed and accounting for 86% of CF genes in the native Caucasian population of the United Kingdom. ΔF508 is the most common at 753% of CF mutations (range 56.5–83.7%), followed by G551D (3.08%; range 0.71–7.60%), G542X (1.68%; range 0.85–3.66%), 621 + 1 (G>T) (0.93%; range 0.41–3.16%), 1717-1(G>A) (0.57%; range 0.17-1.14%), 1898+ 1)(G>A) (0.46%), R117H (0.46%), N1303K (0.46%), and R553X (0.46%). The data show a clear geographical variation in the distribution of some of the mutations, most notably a marked regional variation in the distribution of 621 + 1 (G>T)and 1989+ 1(G>A), which are both apparently more frequent in Wales. R560T and R117H appear to be more frequent in Ireland and Scotland, and G551D more frequent in Scotland. In summary, these data illustrate that the mutations present within a particular population need to be defined in order to provide meaningful carrier screening and testing for rare mutations in affected individuals. Furthermore, it is apparent that the ethnic origin of a patient, even within a small country such as the United Kingdom, should be taken into account. © 1995 Wiley-Liss, Inc.

Derivation of pressure gradients from magnetic resonance angiography using multi-resolution segmentation

Abstract: The use of magnetic resonance (MR) angiography in cardiovascular assessment is steadily increasing on the merits of sensitivity to disease states, lack of ionising radiation and iodinated contrast agent, and widespread applicability to the vasculature. Because MR angiograms are usually obtained as a data set of parallel images, visualisation and analysis require post-processing. The sparsity of the macro-vasculature relative to the data volume. Coupled with the still variable results of MR studies has led to general very few widely used processing and viewing tools in clinical practice. We have implemented a model based multiresolution image segmentation technique which makes use of the velocity field information in phase contrast MR angiograms, and an a priori assumption that locally, blood vessels appear as line segments. The list structure of the resulting segmentation can be used efficiently in subsequent image analysis and processing. Within this segmentation, flow direction, vessel axis, diameter and velocity estimates can be made. We demonstrate its use in extracting vessels from patient data and in the calculation of pressure gradients in a model stenosis.

Multiresolution approach to flow feature extraction from phase contrast magnetic resonance angiography

Abstract: The authors considered a multi-resolution, model based segmentation method for magnetic resonance angiography (MRA). It is a spatial domain based technique and an extension to 3D of a 2D curve segmentation method reported elsewhere. The method has been demonstrated to produce a concise symbolic description of the MRA data (in the form of vessel centre lines) and is efficient in its computational complexity being equivalent in processing to filtering by a 3*3*3 kernel, and based on a generalised and flexible image model which has great potential as a basis for both qualitative and quantitative assessment of MRA data. The work and results presented thus far are preliminary and currently there are several areas where consolidation and enhancement is necessary. There is a need to assess the levels of noise in the data in situ, to better control the confidence levels used for the hypothesis testing. Curve tracing is currently done probabilistically based purely on the local curvature. By considering the physical measurements of the data being imaged, e.g. speed of blood and the vessel diameters, local connectivity could be established using a conservation of mass constraint. Also, there is need to explicitly define bifurcations as part of the signal model. With regards to visualisation, some experimentation has already been carried out to represent flow direction and using the multiresolution vectors for generating filtered maximum intensity projections and predicting probable flow. The segmentation is also being applied to the estimation of blood pressure gradients in vivo.