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Biomedical subjects

M Goodfield

Publications and source records attributed to M Goodfield.

At least 19 recordsLinked to original sources
PubMed2004

Double-blind, randomised, multicentre, parallel group study comparing a 1% coal tar preparation (Exorex) with a 5% coal tar preparation (Alphosyl) in chronic plaque psoriasis.

BACKGROUND: Exorex lotion is a novel formulation of prepared coal tar indicated for the treatment of psoriasis. OBJECTIVES: To compare the efficacy and tolerability of 1% prepared coal tar lotion versus 5% coal tar extract in patients with mild to moderate plaque psoriasis. PATIENTS AND METHODS: This was a double-blind, randomised controlled study. Patients initially entered a 7-day washout period, during which they applied a yellow soft paraffin plus emulsifying wax ointment used as an emollient three times a day to their plaques. They were then randomised to receive treatment with 1% coal tar (Exorex) lotion or 5% conventional coal tar lotion (Alphosyl), three times a day for 12 weeks. Both treatment groups continued to apply the emollient throughout the duration of the study. Two target plaques were selected at entry for assessment. The clinical measures used were: 1) Total Sign Score (TSS), the sum of 5-point rating scores for erythema, induration and scaling averaged for the two target plaques (range 0-12), 2) the Psoriasis Area and Severity Index (PASI), and 3) patient and investigator 7-point global assessments of improvement at 12 weeks. Patients were assessed at 0, 4, 8 and 12 weeks during the treatment period or at the point of withdrawal. Spontaneously reported and observed adverse events were noted. RESULTS: Three hundred and twenty four of 338 randomised patients were evaluable (ITT analysis): 158 patients received 1% coal tar lotion and 166 patients received conventional coal tar. Both groups showed decreases from baseline to end of treatment in mean TSS (decrease of 2.4 points from 5.6 to 3.2 with 1% coal tar lotion and 1.8 points from 5.5 to 3.7 with conventional coal tar), and mean PASI (decrease of 2.4 points with 1% coal tar lotion and 1.5 points with conventional coal tar). Two hundred and twenty eight patients completed the full course of treatment. There was a statistically significant treatment difference in the percentage change in mean TSS at week 12, in favour of 1% coal tar lotion (-10.6%, 95% CI -20.6% to -0.5%, p=0.04). There was also a difference between treatments in the change in mean PASI in favour of 1% coal tar that was of borderline statistical significance (-11.7%, 95% CI -23.8% to 0.4%, p=0.06). Investigator global assessments also favoured 1% coal tar lotion (38% vs. 27% of patients showed clearance or marked improvement). The 1% coal tar lotion had a similar safety profile to 5% conventional coal tar lotion with the majority of treatment-related events being mild to moderate in severity. CONCLUSIONS: 1% coal tar lotion is more effective than a conventional coal tar lotion in mild to moderate psoriasis and may be preferred for first-line topical treatment.

Adolescent↗
PubMed2004

Efficacy of treatment with calcipotriol/betamethasone dipropionate followed by calcipotriol alone compared with tacalcitol for the treatment of psoriasis vulgaris: a randomised, double-blind trial.

BACKGROUND: A two-compound product containing calcipotriol 50 microg/g and betamethasone dipropionate 0.5 mg/g (Daivobet, Dovobet) has been demonstrated to be an effective, once daily, treatment for psoriasis vulgaris. OBJECTIVE: To compare the efficacy and safety of treatment with the two-compound product for 4 weeks followed by calcipotriol for 4 weeks, with that of tacalcitol for 8 weeks in patients with stable psoriasis vulgaris. METHODS: 501 patients were randomised to double-blind treatment with the two-compound product followed by calcipotriol 50 microg/g once daily, or to tacalcitol 4 microg/g once daily. RESULTS: Treatment with the two-compound product/calcipotriol was significantly more effective than tacalcitol in terms of mean percentage PASI reduction (65.0 vs. 33.3% at week 4 and 59.0 vs. 38.4% at week 8; p < 0.001 for both). CONCLUSION: A treatment regimen comprising calcipotriol/betamethasone ointment (Daivobet) for 4 weeks followed by calcipotriol for 4 weeks is superior to tacalcitol ointment for 8 weeks in patients with psoriasis vulgaris.

Administration, Topical↗
PubMed2003

The role of somatic mutation in determining the affinity of anti-DNA antibodies.

Combinatorial antibody libraries were constructed from the spleen of a patient with concomitant systemic lupus erythematosus and idiopathic thrombocytopenia. Following selection of the libraries with DNA, a panel of 15 anti-DNA Fabs was isolated. Sequence analysis of these antibodies coupled with measurements of their affinities for ss- and dsDNA were used to investigate the role of somatic mutation in affinity maturation of the anti-DNA response. Examination of the germline genes used by these Fabs supports previous studies that suggest there is no restriction of the gene usage in the anti-DNA response. However, data are presented indicating that VH3 genes and the A27 V(kappa) paired with the J(kappa)1 may be over-expressed in the anti-DNA repertoire. Analysis of the role of somatic mutation in increasing affinity for DNA indicates that affinity maturation has occurred and suggests that the CDR1 and CDR2 of the heavy chain are of importance in this process.

Adult↗
PubMed2000

The identification of endothelial cell autoantigens.

The identity of many endothelial cell autoantigens remains unclear. This study has used human monoclonal anti-endothelial cell autoantibodies isolated from patients with SLE to identify endothelial autoantigens. Thirteen antibodies reactive with endothelial cell membrane preparations were isolated and cloned, one of which has previously been demonstrated to be pro-inflammatory. Western blotting demonstrates that these antibodies recognize a variety of proteins in endothelial cell membrane preparations. Further characterization of five antibodies by cDNA library screening, immunofluorescence and Western blotting proves that two of these antibodies recognized the cytoskeletal proteins tubulin and vimentin. A further antibody identified a clone derived from human collagenase, an identification supported by Western blotting. The multiple clones selected by other antibodies are not compatible with the molecular weight of the antigen recognized in Western blotting studies. This study has clearly identified two endothelial cell autoantigens present in membrane preparations and provides strong evidence as to the identity of a third.

Antibodies, Monoclonal↗
PubMed1999

The relationship between pityriasis rubra pilaris and inflammatory arthritis: case report and response of the arthritis to anti-tumor necrosis factor immunotherapy.

Pityriasis rubra pilaris (PRP) refers to a group of erythematous, scaling dermatologic conditions that have been associated with seronegative arthritis. We report a case of polyarthritis in a young man with PRP in which magnetic resonance imaging suggested an entheseal-based pathology for the joint disease. The arthritis, but not the skin condition, demonstrated dramatic response to anti-tumor necrosis factor immunotherapy.

Adolescent↗
PubMed1998

Does the CDR3 of the heavy chain determine the specificity of autoantibodies in systemic lupus erythematosus?

Many factors are involved in the recognition of autoantigens by autoanti-bodies, including the use of specific germline genes, the sequence and structure of the CDR3 of the heavy chain, somatic mutation and selective heavy and light chain pairing. However, the relative importance of these factors remainsunclear. This study reports the results of sequence analysis of two anti-endothelial cell antibodies that recognise the same antigen. Sequence analysis of these antibodies shows that they use the same heavy chain germline genes as two anti-DNA antibodies but differ significantly in the sequence of the CDR3. Furthermore, one of the antibodies uses a light chain germline gene combination that has been reported for three anti-DNA antibodies. One of these antibodies shows significant mutation in the CDR2 of the heavy chain. Peptide analysis suggests that the differences between these anti-DNA and anti-endothelial cell antibodies result in consistent structural differences that may reflect the nature of the antigen recognised.

Amino Acid Sequence↗
PubMed1997

Optimal management of chronic leg ulcers in the elderly.

Chronic leg ulceration is a very common clinical problem in the elderly. Good management depends entirely on making an accurate diagnosis, and planning treatment after considering all aspects of patient well-being. All elderly patients with leg ulcers benefit from an assessment of their vascular status, since the effects of gravity influence treatment and healing irrespective of the diagnosis. The most common causes of ulceration are venous and arterial disease. Diabetes mellitus, pressure, vasculitis, metabolic abnormalities and skin cancer are all unusual causes of leg ulceration, but must be considered in the differential diagnosis. Almost all patients with ulcerated legs benefit from the use of compression bandaging at a level appropriate to their vascular status. In patients with venous ulcers, this can be achieved with a number of bandaging techniques; however, multilayer bandaging appears to be the most cost-effective means available, particularly when combined with community-based leg ulcer clinics. The effects of oral drug therapy for venous and arterial disease have been disappointing. Local dressings are important in ulcers that are not suitable for compression therapy. The choice of dressing depends on the nature of the ulcer and the tolerability of the dressing for the patient.

Administration, Oral↗
PubMed1995

Methotrexate for the treatment of severe mucocutaneous lupus erythematosus.

We report three women with severe, chronic mucocutaneous lupus erythematosus who showed a significant improvement during oral methotrexate therapy; the improvement was sustained after the drug was discontinued. Their disease had previously been refractory to a wide range of conventional systemic immunosuppressive therapies. Other treatments were progressively withdrawn, and control was maintained, for a variable length of time, with methotrexate alone, or with a small dose of prednisolone.

Administration, Oral↗
PubMed1994

Skin lesions in psoriasis.

Psoriatic skin disease is common; it occurs at all ages and co-exists with joint disease in approximately 10% of cases. All areas of skin, scalp and nails may be involved. In the typical case, the skin lesions are easy to recognize. Atypical forms of skin involvement and lesions at unusual sites are less easily diagnosed by non-specialists. The cause is unknown, but there is a clear genetic element, with external factors being important in precipitation and exacerbations of the condition. Topical treatment is successful in most patients, but in resistant cases combinations of systemic therapy and ultraviolet radiation usually give good control. Although there is no cure, the majority of sufferers live normal lives and, with the exception of severe erythrodermic or generalized pustular psoriasis, there is no mortality. Morbidity, particularly social and occupational, is more of a problem than is often acknowledged.

Arthritis, Psoriatic↗
PubMed1994

Investigations of the 'active' edge of plaque psoriasis: vascular proliferation precedes changes in epidermal keratin.

We have investigated markers of epidermal proliferation and differentiation in terms of keratin expression, the morphology of the cutaneous vasculature, and numbers of cutaneous mast cells, in patients with chronic plaque psoriasis. Using the phenomenon of the 'active edge', we have studied these features in the psoriatic plaque itself, and in the clinically normal active and inactive edges of the same plaque. Our results confirm the anticipated changes in keratin profiles, mast cell numbers and psoriatic morphology of the vasculature within the plaque itself. They further indicate that the vascular changes precede the epidermal and mast cell features at the active edge, and that the inactive edge is inactive for all of these variables. Mediators responsible for the vascular proliferation and elongation must be present in increased amounts at the active edge when compared with the inactive, and include locally produced and circulating factors.

Cell Count↗
PubMed1994

A pathogenic role for endothelin in Raynaud's phenomenon?

Plasma endothelin response to a standardized cold challenge in 7 patients with primary Raynaud's phenomenon and 7 controls using a sensitive radioimmunoassay was measured. There was no difference between resting levels of plasma endothelin in patients with primary Raynaud's phenomenon (2.6 fmol/ml) and controls (2.4 fmol/ml). A decrease in plasma endothelin levels in both groups of patients during the initial phase of the cold challenge was detected; this was more pronounced in the patients with Raynaud's phenomenon. These results suggest that there is no persistent stimulus to overproduction of endothelin. The fall in levels in patients with Raynaud's phenomenon during the initial phase of the cold challenge might suggest that a different vasoconstrictive factor is initiating the start of the vasospastic process, with the decreased endothelin levels being a reactive response to increased vasoconstriction produced by this alternative factor.

Adult↗
PubMed1989

Cold-induced skin disorders.

Skin conditions caused by cold temperatures are not uncommon. Recognition is generally easy at a clinical level, but awareness of the much less common underlying disorders is important. Treatment, both physical and pharmacological, is aimed at keeping the body warm and maintaining vasodilation.

Chilblains↗
PubMed1989

Active and inactive edges of psoriatic plaques: identification by tracing and investigation by laser--Doppler flowmetry and immunocytochemical techniques.

In plaque psoriasis it is likely that biochemical and ultrastructural changes precede the appearance of the typical plaque that is recognizable clinically. Currently, no technique exists by which the very early changes in psoriasis can be investigated. We report a method in which plaques of psoriasis are serially traced to identify their advancing edge. Eight-two untreated plaques from 15 patients and 38 treated plaques from 6 patients were traced over a three-week period; 65% of untreated and 57% of treated plaques showed consistent asymmetrical movement, allowing identification of an active and an inactive edge of each plaque. Using this technique, the active edge of two or more plaques was identified in each of ten patients. Blood flow measured by laser Doppler flowmetry indicated a 2.5-to-4.5-fold increase in cutaneous blood flow at the active edge compared with the inactive edge of each plaque. Punch biopsies from the sites investigated by laser Doppler flowmetry were examined by routine histology and monoclonal antibody immunohistology, but revealed no epidermal change and no T lymphocytic excess when the two areas were compared. We infer from these findings that the earliest change in a developing plaque is an increased blood flow, probably associated with a diffusable, and possibly humoral, initiating factor that accumulates at the active edge, stimulating transformation of normal skin to psoriatic plaque.

Antibodies, Monoclonal↗