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Biomedical subjects

G Lawton

Publications and source records attributed to G Lawton.

At least 19 recordsLinked to original sources
PubMed2006

Elongational flow induced ordering in surfactant micelles and mesophases.

We have used small angle neutron scattering, SANS, to investigate the elongational flow induced ordering in surfactant micelles and mesophases. Spatially resolved SANS measurements have been used to determine the distribution of orientational ordering over the flow velocity pattern in an elongational flow cell, and comparison with the effects of shear flow are made. Two different surfactant systems have been studied, the charged wormlike mixed micelles of hexaethylene monododecyl ether, C16E6/hexadecyl trimethylammonium bromide, C16TAB (3% C16E(6)/5 mol% C16TAB), and the Lalpha lamellar phase of C16E6 (50.6 wt% C16E6 at 55 degrees C), and a substantially different response is observed. The orientational distribution of the Lalpha lamellar phase of C16E6 reflects the flow velocity pattern distribution within the cell, whereas for the wormlike mixed micelles of C16E6/C16TAB this is not the case, and this is associated with the shear thinning behavior of that system.

Journal Article↗
PubMed2006

Cross-cultural validity of FIM in spinal cord injury.

OBJECTIVE: To analyse cross-culture validity of the Functional Independence Measure (FIM) in patients with a spinal cord injury using a modern psychometric approach. SETTINGS: A total of 19 rehabilitation facilities from four countries in Europe. PARTICIPANTS: A total of 647 patients at admission, median age 46 years, 69% male. METHODS: Data from the FIM, collected on inpatient admission, was fitted to the Rasch model. A detailed analysis of scoring functions of the seven categories of the FIM items was undertaken before to testing fit to the model. Categories were rescored where necessary. Fit to the model was assessed initially within country, and then in the pooled data. Analysis of differential item functioning (DIF) was undertaken in the pooled data for each of the FIM motor and social cognitive scales, respectively. Final fit to the model was tested for breach of local independence by principle components analysis (PCA). RESULTS: The present scoring system for the FIM motor and cognitive scales, that is a seven category scale, was found to be invalid, necessitating extensive rescoring. Following this, DIF was found in a number of items within the motor scale, requiring a complex solution of splitting items by country to allow for the valid pooling of data. Five country-specific items could not be retained within this solution. The FIM cognitive scale fitted the Rasch model after rescoring, but there was a substantial ceiling effect. CONCLUSIONS: Data from the FIM motor scale for patients with spinal cord injury should not be pooled in its raw form, or compared from country to country. Only after fit to the Rasch model and necessary adjustments could such a comparison be made, but with a loss of clinical important items. The FIM cognitive scale works well following rescoring, and data may be pooled, but many patients were at the maximum score.

Activities of Daily Living↗
PubMed2005

The use of recombinant activated factor VII in the control of haemorrhage following blunt pelvic trauma.

This article reports two cases of severe blunt pelvic trauma associated with road traffic accidents, where the patients developed significant bleeding and haemodynamic instability, poorly responsive to conventional management. Both patients required massive transfusion of blood products with a resultant dilutional coagulopathy. In each case, a single dose of recombinant activated factor VII (rFVIIa) was used to achieve haemostatic control, with a subsequent decrease in blood product requirements and improvement in haemoglobin concentration and clotting profile.

Accidents, Traffic↗
PubMed2003

The Behcet's disease activity index.

OBJECTIVE: To identify a subset of clinical features of Behçet's disease (BD) that can be summated to form an overall index of disease activity appropriate for clinical and research use internationally. METHODS: Completed Behçet's Disease Current Activity Forms were collected from a total of 524 patients with BD from five countries. The data from 14 questions on the form were subjected to Rasch analysis to establish whether these items form a hierarchical and unidimensional scale of disease activity, both within and between countries. RESULTS: The data showed a good fit to the Rasch model within three countries using a dichotomous scoring function. However, when the data from these three countries were pooled, the fit to the model was poor. Cross-cultural differential item functioning (DIF) was found in seven items in the pooled data. When the items with DIF by country were separated and two items were removed, the resulting 26-item scale showed a good fit to the Rasch model. CONCLUSIONS: Within Turkey, Korea and the UK, the 14 items can be summated to give an index of disease activity. Analysis of the pooled data confirmed that the index is not suitable for comparison between countries or for pooling of data in the raw form, but after fitting the data to the Rasch model such comparisons can be made. This gives a scaling tool that is quick and easy to use in the clinical situation.

Behcet Syndrome↗
PubMed1997

Inhibition of bovine nasal cartilage degradation by selective matrix metalloproteinase inhibitors.

N-terminal analysis of aggrecan fragments lost from bovine nasal cartilage cultured in the presence of recombinant human interleukin 1alpha revealed a predominant ARGSVIL sequence with an additional ADLEX sequence. Production of the ARGSVIL-containing fragments has been attributed to the action of a putative proteinase, aggrecanase. The minor sequence (ADLEX) corresponds to a new reported cleavage product; comparison of this sequence with the available partial sequence of bovine aggrecan indicates that this is the product of a cleavage occurring towards the C-terminus of the protein. Matrix metalloproteinase (MMP) inhibitors inhibited aggrecan loss from bovine nasal explants incubated in the presence of recombinant human interleukin 1alpha. A strong correlation between inhibition of aggrecan metabolism and inhibition of stromelysin 1 (MMP 3) (r=0.93) suggests a role for stromelysin or a stromelysin-like enzyme in cartilage aggrecan metabolism. However, the compounds were approx. 1/1000 as potent in inhibiting aggrecan loss from the cartilage explants as they were in inhibiting stromelysin. There was little or no correlation between inhibition of aggrecan metabolism and inhibition of gelatinase B (MMP 9) or inhibition of collagenase 1 (MMP 1). Studies with collagenase inhibitors with a range of potencies showed a correlation between inhibition of collagenase activity and inhibition of collagen degradation in the cartilage explant assay. This indicates that in interleukin 1alpha-driven bovine nasal cartilage destruction, stromelysin (or a closely related enzyme) is involved in aggrecan metabolism, whereas collagenase is principally responsible for collagen degradation.

Aggrecans↗
PubMed1993

Inhibitors of protein kinase C. 3. Potent and highly selective bisindolylmaleimides by conformational restriction.

The protein kinase inhibitor staurosporine has been used to design a series of selective bisindolylmaleimide inhibitors of protein kinase C (PKC). Guided by molecular graphics, conformational restriction of the cationic side chain has led to ATP competitive inhibitors of improved potency and selectivity. Two compounds have been further evaluated and were shown to inhibit PKC of human origin and prevent T-cell activation in a human allogeneic mixed lymphocyte reaction. One of these compounds was orally absorbed in mice and antagonized a phorbol ester induced paw edema in a dose-dependent manner. This compound also selectively inhibited the secondary T-cell mediated response in a developing adjuvant arthritis model in rats and provides evidence for the potential use of PKC inhibitors as therapeutic immunomodulators.

Alkaloids↗
PubMed1992

Inhibitors of protein kinase C. 2. Substituted bisindolylmaleimides with improved potency and selectivity.

A hypothetical mode of inhibition of protein kinase C (PKC) by the natural product staurosporine has been used as a basis for the design of substituted bisindolylmaleimides with improved potency over the parent compound. Structure-activity relationships were consistent with the interaction of a cationic group in the inhibitor with a carboxylate group in the enzyme, and the most potent compound had a Ki of 3 nM. The inhibitors were competitive with ATP but inhibited cAMP-dependent protein kinase (PKA) only at much higher concentrations despite the extensive sequence homology between the ATP-binding regions of PKA and PKC. Three compounds were evaluated further and found to inhibit a human allogeneic mixed lymphocyte reaction pointing to the potential utility of PKC inhibitors in immunosuppressive therapy. One of these compounds was orally absorbed in the rat and represents an attractive lead in the development of PKC inhibitors as drugs.

Animals↗
PubMed1992

Oral, anti-inflammatory activity of a potent, selective, protein kinase C inhibitor.

The protein kinase C family of enzymes is thought to be important in mediating signal transduction. Ro 31-8830 is a novel, potent inhibitor of protein kinase C, derived from the non-selective protein kinase inhibitor staurosporine. In this paper we demonstrate the selectivity of Ro 31-8830 for protein kinase C over other protein kinases and its ability to inhibit protein kinase-C-mediated events in platelets and lymphocytes. In addition, we describe a novel system for the in vivo evaluation of inhibitors of protein kinase C, and we demonstrate the oral anti-inflammatory activity of Ro 31-8830. This finding has implications for the treatment of inflammatory disorders in the clinic.

Administration, Oral↗
PubMed1992

Inhibitors of protein kinase C. 1. 2,3-Bisarylmaleimides.

The design and synthesis of a series of novel inhibitors of protein kinase C (PKC) is described. These 2,3-bisarylmaleimides were derived from the structural lead provided by the indolocarbazoles, staurosporine and K252a. Optimum activity required the imide NH, both carbonyl groups, and the olefinic bond of the maleimide ring. 2,3-Bisindolylmaleimides were the most active, and the potency of these was improved by a chloro substituent at the 5-position of one indole ring (compound 28, IC50 0.11 microM). In a series of (phenylindolyl)maleimides, nitro compound 74 was most active (IC50 0.67 microM). Naphthalene 19 and benzothiophene 21 showed greater than 100-fold selectivity for inhibition of PKC over the closely related cAMP-dependent protein kinase (PKA).

Animals↗