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Biomedical subjects

D J Gawkrodger

Publications and source records attributed to D J Gawkrodger.

At least 73 records · Page 4Linked to original sources
PubMed1998

Foot dermatitis in children: causative allergens and follow-up.

Allergic contact dermatitis from shoes may have a typical pattern of presentation, but we have found that the distribution of dermatitis is often unhelpful in establishing the diagnosis. In this study, we aimed to define the features of foot dermatitis in children and to assess its outcome, in comparison to adults with foot eruptions. Relevant allergens were found in 15 out of 29 children and 26 out of 57 adults with foot eruptions. The most common allergens in children were rubber chemicals and topical medicaments. Adults showed a similar pattern, but also reacted to clothing dyes. The prognosis in both groups was good, with the dermatitis improving or resolving in 2/3.

Adolescent↗
PubMed1998

alpha-MSH and melanogenesis in normal human adult melanocytes.

Normal human skin melanocytes do not pigment consistently to alpha-melanocyte stimulating hormone (alpha-MSH) in culture. The aim of this study was to establish media conditions in which to obtain a reproducible melanogenic response to alpha-MSH in these cells. Twenty-five media of varying mitogen composition were examined. As previously noted by other workers, melanocyte morphology and proliferation are greatly affected by media composition. However, under the majority of media conditions that supported melanocyte survival and proliferation, cells did not respond to alpha-MSH with any consistent increase in dopa oxidase activity or melanin content. In only one medium condition, where basic fibroblast growth factor (bFGF) was the sole mitogen present, alpha-MSH induced both an increase in dopa oxidase activity (at 48%) and in melanin content (of 283%).

1-Methyl-3-isobutylxanthine↗
PubMed1997

Patch testing in children and adolescents: five years' experience and follow-up.

BACKGROUND: Allergic contact dermatitis in children is a significant clinical problem. Little information is available concerning the value of patch testing and the outcome in these children. OBJECTIVE: Our purpose was to assess the value of patch testing in children and the outcome of allergic contact dermatitis in childhood. METHODS: Clinical data on 83 children patch tested during a 5-year period were assessed. Clinical follow-up on 68 subjects was performed. RESULTS: Overall, 41 children had one or more allergic reactions (49%). Reactions to metals, topical preparations, and food additives were common. The clinical outcome at 6 months was significantly better for 36 children with a relevant allergen on patch testing than in 32 with no allergen or no relevant allergen (p = 0.006). CONCLUSION: Patch testing is useful in the management of children suspected of having an allergic contact dermatitis. Patch testing and subsequent allergen avoidance may improve the prognosis in children with a relevant contact allergen.

Administration, Cutaneous↗
PubMed1997

Immunoprecipitation of melanogenic enzyme autoantigens with vitiligo sera: evidence for cross-reactive autoantibodies to tyrosinase and tyrosinase-related protein-2 (TRP-2).

In the present study we describe the detection of TRP-2 antibodies in vitiligo patients using in vitro 35S-labelled human TRP-2 in a radioimmunoassay. Of 53 vitiligo sera examined in the assay, three (5 9%) were found to be positive for TRP-2 antibodies. In contrast, 20 control sera, sera from 10 patients with Hashimoto's thyroiditis and sera from 10 patients with Graves' disease were all negative. All three patients positive for TRP-2 antibodies (mean age 54 years, age range 50-63 years) had had vitiligo of the symmetrical type for more than 1 year and all of them also had an associated autoimmune disorder: Graves' disease in one and autoimmune hypothyroidism in two. In addition, antibodies to the melanogenic enzyme tyrosinase were present in their serum. To examine any immunological cross-reactivity between TRP-2 and tyrosinase, the three vitiligo sera positive for TRP-2 antibodies were preabsorbed with COS-7 cell extract containing either expressed TRP-2 or tyrosinase, and subsequently used in the radioimmunoassay. These absorption studies indicated that preincubation with both proteins inhibited the immunoreactivity of the positive sera in the immunoassay using in vitro translated 35S-TRP-2. This antibody cross-reactivity suggests the humoral response to the two melanogenic enzymes in these patients may not be entirely independent.

Absorption↗
PubMed1997

Detection of tyrosinase autoantibodies in patients with vitiligo using 35S-labeled recombinant human tyrosinase in a radioimmunoassay.

Tyrosinase antibodies recently have been reported to occur frequently in patients with vitiligo. We describe the detection of tyrosinase antibodies in vitiligo patients using in vitro 35S-labeled human tyrosinase in a radioimmunoassay. Of 46 vitiligo sera examined in the assay, five (10.9%) were found to be positive for tyrosinase antibodies. In contrast, 20 control sera and sera from 10 patients with Hashimoto's thyroiditis were negative. Four of the sera positive in the radioimmunoassay were also positive in an ELISA using mushroom tyrosinase as antigen. Absorption studies indicated that pre-incubation with mushroom tyrosinase absorbed out the immunoreactivity of the positive sera in the radioimmunoassay, suggesting cross-reactivity, but this absorption was never complete, indicating that there are tyrosinase antibodies in human sera that do not react with the mushroom protein. There was no obvious association between the presence of tyrosinase antibodies and the age of the patients (range: 22-62 y), their duration of disease (range: 5-20 y), or the type of vitiligo (one segmental, one symmetrical/periorificial, three symmetrical), although the three patients with the highest antibody levels also had an associated autoimmune disorder (one with Graves' disease; two with autoimmune hypothyroidism). The results confirm that tyrosinase autoantibodies are present in the sera of vitiligo patients but at a low frequency. The technique described is sensitive and quantitative and allows the detection of conformational epitopes. It will be useful in longitudinal studies to determine the relation between the clinical features of vitiligo and tyrosinase antibody levels.

Adult↗
PubMed1997

Azathioprine in dermatology: a survey of current practice in the U.K.

Azathioprine has an important role in treatment of many inflammatory dermatoses. In view of the current emphasis on evidence-based medicine, we performed a questionnaire-based survey to establish current practice in the use of azathioprine by consultant dermatologists and associate specialists in the U.K. The response rate was 68%. In contrast with the manufacturer's recommendation, our data provide evidence that azathioprine is useful in the treatment of a wide variety of dermatological diseases. However, there is still a need for controlled trials in some conditions. The most common conditions treated were pemphigoid, pemphigus and atopic eczema. In addition, we found that only 13% of dermatologists prescribe azathioprine according to body weight. Most dermatologists felt that azathioprine was well tolerated. No one tested for thiopurine methyltransferase (TPMT) activity, which is thought to be a predictor of severe myelosuppression. The combination of prescribing azathioprine according to body weight and measuring TPMT activity would optimize efficacy and minimize potential severe myelotoxicity.

Azathioprine↗
PubMed1997

Contact sensitivity in pruritus vulvae: patch test results and clinical outcome.

BACKGROUND: Persistent vulval pruritus is common and may not be associated with signs of a primary vulval dermatosis. Patients with established vulval disease may develop contact sensitivity as a secondary problem after the application of topical therapy. OBJECTIVE: A retrospective study was performed to establish the prevalence of allergic contact dermatitis in patients with pruritus vulvae. In addition, the results of patch testing in women with vulval lichen sclerosus were compared with those in patients with primary pruritus vulvae and essential vulvodynia. METHODS: Over a 5-year period, 121 women with vulval problems were patch tested to the European Standard Series, selected preservatives, perfumes, local anesthetics, medicaments, and a vulval battery. RESULTS: Fifty-seven patients (49%) had one or more relevant allergic positive reactions. Medicaments or their constituents were the most common allergens to give reactions. Seven of the 16 patients (44%) with lichen sclerosus had positive reactions. Symptoms resolved or improved significantly in 67 patients (55.4%) overall. Six of the seven women with lichen sclerosus who had positive reactions noted an improvement in their symptoms. Patients who had a relevant allergy were much more likely to improve than those whose tests were negative (p < 0.001). CONCLUSION: Patients with pruritus vulvae and lichen sclerosus are at high risk of contact sensitivity. Patch testing is useful in the management of these patients and many can be helped by allergen avoidance.

Administration, Topical↗
PubMed1996

Delayed and immediate orofacial reactions following contact with rubber gloves during dental treatment.

Allergic reactions during or after dental examination are uncommon. However, such reactions may be serious and distressing. Allergy to local anaesthetics and dental materials may be considered, but reactions to rubber in gloves worn by the dentist should be remembered. Two patients are reported who experienced symptoms following contact with rubber gloves worn by their dentists, with skin tests subsequently showing an allergic reaction to glove constituents, and in one case latex. With the increasing use of rubber gloves by dental and medical personnel, reactions in sensitised patients are likely to become more common. In patients with a history of symptoms related to dental work, it is important to remember delayed and immediate reactions to rubber.

Dermatitis, Allergic Contact↗
PubMed1996

Investigation of the influence of extracellular matrix proteins on normal human melanocyte morphology and melanogenic activity.

Several studies have indicated that extracellular matrix (ECM) proteins can influence melanocyte behaviour in vitro. However, the choice of medium is known to have a profound effect on melanocyte behaviour and it is currently difficult to ascribe which reported effects are due to ECM proteins and those which are attributable to the medium used in these different studies. The purpose of this study was to learn more about the influence of ECM proteins on melanocyte function by examining a range of cell-derived and individual ECM proteins for their impact on melanocyte tyrosinase activity in cells cultured under conditions of varying mitogenic drive. We found that ECM derived from human dermal fibroblasts, bovine endothelial cells and a human endothelial cell line as well as collagen I, collagen IV, fibronectin, and to a lesser extent laminin, were all capable of increasing tyrosinase activity in cultures of normal melanocytes. Effects of these ECM were seen most consistently in media with relatively few mitogens, for example ECM proteins influenced melanocyte morphology and this was seen most readily in cells cultured in medium without any mitogens (which ordinarily fails to support melanocyte survival). This study illustrates that ECM proteins can influence melanocyte morphology, proliferation, and tyrosinase activity in vitro and supports a possible role of ECM proteins in the regulation of melanocyte function in vivo.

Cell Count↗
PubMed1996

Prognosis of occupational hand dermatitis in metalworkers.

Hand dermatitis is common in workers employed in the cutting and grinding of metals. Previous studies have given conflicting results on the prognosis of this common occupational disease. This study was designed to determine the prognosis of hand dermatitis in metalworkers and the responsible allergens. A questionnaire survey was conducted on 64 patients seen between 1 and 5 years previously in the contact dermatitis clinic. Of the 51 patients responding, 82% still had hand dermatitis. There was no difference in outcome between those who continued to work with metals and oils, and those who had changed their occupation. Hand dermatitis in metalworkers carries a poor prognosis, with most workers remaining symptomatic even if they no longer had occupational exposure to metals or oils. This study also demonstrates that biocides are the most important allergen group in the aetiology of hand dermatitis in metalworkers.

Adult↗
PubMed1996

Nickel dermatitis: how much nickel is safe?

The Nickel Directive will become law in the countries of the European Union in 1996. This directive states that the concentration of nickel in post assemblies (used after ear piercing) may not exceed 0.05%, that products which come into direct and prolonged contact with the skin, e.g. earrings, watchstraps or zippers, may not release greater than 0.5 microgram/cm2/week, and that nickel release from coated products will not exceed this level after 2 years of normal use. The data relating to the threshold for reacting to nickel and the levels of nickel release from nickel-containing objects, are considered in this review. Although the level of 0.5 microgram/cm2/week is one below which a minority of nickel-allergic subjects will react, it is not safe in every nickel-sensitive individual. This level of nickel release is currently exceeded by many nickel-containing alloys and jewelery items that are made from high-sulfur stainless steel, and manufacturers are going to have to change the composition of jewelery to comply with the directive.

Alloys↗
PubMed1996

Chromium- and nickel-induced cytotoxicity in normal and transformed human keratinocytes: an investigation of pharmacological approaches to the prevention of Cr(VI)-induced cytotoxicity.

Chromium and nickel compounds cause irritancy but can also induce allergic contact dermatitis. The aims of this study were to characterize the direct cytotoxic effects of Cr(VI), Cr(III) and Ni(II) salts on keratinocytes, and to investigate pharmacological strategies to protect cells against Cr(VI)-induced cytotoxicity. Normal human keratinocytes and the HaCaT keratinocyte cell line were used. Cell viability was assessed by neutral red dye uptake, the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) eluted stain assay and measurement of lactate dehydrogenase (LDH) activity in the medium. The assays varied slightly in their sensitivities (neutral red > MTT > LDH) although all three gave similar results. In both cell types, the relative order of cytotoxicity of the salts was Cr(VI) >> Ni(II) > Cr(III). There were no major differences between chromium salts of a common valency. Normal human keratinocytes showed a much greater variability in their response to Cr(VI) and Ni(II) salts than HaCaT cells and were generally more resistant to Cr(VI)- and Ni(II)-induced cytotoxicity. Several drugs were screened for their potential to protect both cell types against the cytotoxic effects of Cr(VI), specifically the reducing agents ascorbic acid, cysteine and glutathione, and the Cr(VI) cellular uptake inhibitors 4,4'-diisothiocyanato-2,2'-stilbenedisulphonic acid (DIDS) and 4-acetamido-4'-isothiocyanato-2,2'-stilbenedisulphonic acid (SITS). All five drugs provided concentration-dependent protection against Cr(VI)-induced cytotoxicity but only ascorbic acid offered complete protection. Several of these pharmacological approaches to the prevention of Cr(VI) cytotoxicity confirm previous clinical studies on the inactivation of Cr(VI), while the clinical potential of others has yet to be investigated.

Ascorbic Acid↗
PubMed1996

Differentiation of human keratinocytes is associated with a progressive loss of interferon gamma-induced intercellular adhesion molecule-1 expression.

Intercellular adhesion molecule-1 (ICAM-1) expression is a necessary requirement for leucocyte/keratinocyte interactions, and keratinocyte upregulation of ICAM-1 is seen in several inflammatory dermatoses. While keratinocytes have a very low constitutive expression of ICAM-1, they can be induced to upregulate ICAM-1 in response to several inflammatory cytokines, such as interferon-gamma (IFN gamma). There is some evidence to suggest that the state of keratinocyte differentiation may influence the level of ICAM-1 expression induced by IFN gamma. The purpose of this study was to investigate the hypothesis that keratinocytes, as they differentiate, may lose their ability to increase their expression of ICAM-1 in response to IFN gamma. Keratinocytes from 13 donors were cultured under conditions which either permitted (Green's medium) or inhibited (MCDB153) differentiation. The ICAM-1 expression in response to IFN gamma was assessed by a sensitive, cell-based, ELISA, and related to the state of differentiation of the cells (as assessed by a quantitative assay for involucrin). While keratinocytes grown in MCDB153 remained responsive to IFN gamma throughout 4 days of culture, the response of keratinocytes grown in Green's medium progressively decreased, so that, by day 3, only a high concentration of IFN gamma (500 U/ml) led to a significant increase in ICAM-1 expression. After 4 days in culture, no upregulation of ICAM-1 was seen. The deterioration in the response of Green's-cultured keratinocytes to IFN gamma mirrored an increase in their expression of involucrin in parallel cultures. Overall, our data demonstrate a progressive loss in the ability of keratinocytes to upregulate ICAM-1 in response to IFN gamma, which is associated with differentiation of these cells. This would support the view that only basal proliferative keratinocytes are responsive to inflammatory cytokines, and play a part in the initiation and amplification of inflammatory reactions in vivo.

Cell Culture Techniques↗
PubMed1996

Contact allergy in patients with oral symptoms: a study of 47 patients.

BACKGROUND: Patients may present with a range of unexplained oral symptoms, and there has been debate about the role of contact sensitivity in these patients. OBJECTIVE: The aim of this study was to review patch test results in patients presenting with oral and perioral symptoms and to determine the relevance of positive reactions. METHODS: Forty-seven patients with oral symptoms were studied. Patients were tested to the European Standard Series and a range of other allergens, including bakery products, dental materials, medicaments, and metals. RESULTS: Sixty-four percent of the patients had one or more positive allergic reactions. In 14 patients (30%), the results were believed to be relevant to their clinical problem. Relevant allergens included metals, rubber chemicals, food additives, and dental products. Symptoms resolved rapidly in all of the 13 patients in whom the source of the offending allergen was removed. CONCLUSION: Patch testing is a useful investigation in patients with unexplained oral and perioral symptoms. Avoidance of the relevant allergen can result in complete resolution of symptoms.

Adolescent↗