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Biomedical subjects

J D Wilkinson

Publications and source records attributed to J D Wilkinson.

At least 19 recordsLinked to original sources

Darier-White disease: a review of the clinical features in 163 patients.

BACKGROUND: Darier's disease is a rare, dominantly inherited genodermatosis; there have not been any large clinical studies of patients with this disease. OBJECTIVE: Our purpose was to document the clinical features in a large group of patients with Darier's disease. METHODS: Data were collected from 163 affected persons. RESULTS: The onset usually occurred between the ages of 6 and 20 years. The disease has a predilection for the skin in seborrheic areas; 96% had acral signs; 6% had hypertrophic flexural involvement; and 13% had oral mucosal lesions. There was no remission. Topical therapy sometimes provided relief of symptoms but had no effect on the progress of the disease. Oral retinoids were effective, but long-term therapy was tolerated poorly. Most patients did not have other medical problems. CONCLUSION: Although Darier's disease is a chronic and unremitting burden, most patients manage to lead a relatively normal life.

Adolescent

Differential effects of structurally unrelated chemical irritants on the density of proliferating keratinocytes in 48 h patch test reactions.

Alterations in the proliferative capacity of human epidermis following topical exposure to structurally unrelated chemical irritants were investigated, with the aim of improving our understanding of the cellular changes that take place during the development of irritant contact dermatitis (ICD). Healthy volunteers were patch tested for 48 h with the following six irritants and their appropriate vehicle and occlusion controls: 5% sodium lauryl sulphate (SLS), 0.5% benzalkonium chloride, 80% nonanoic acid (NAA), 0.02% dithranol, 0.8% croton oil, and 100% propylene glycol (PG). After the degree of inflammation induced was visually graded, biopsy samples were removed and the dividing keratinocytes were identified immunocytochemically by using the monoclonal antibody Ki-67, with quantification being performed on the basis of the number of positive cells/100 basal keratinocytes. Statistically significant increases in the density of proliferating cells occurred in the reactions to SLS, NAA, and PG, whereas, in contrast, dithranol caused a marked decrease in the number of dividing keratinocytes. Overall, the density of proliferating keratinocytes did not show a linear relationship with the visually assessed intensity of inflammation, indicating that the changes observed were related to the chemical nature of the individual irritants and their specific biochemical interactions with the keratinocytes, rather than being the consequence of a generalized inflammatory response. Differential release of epidermal cytokines and mediators by the six irritants may account for these varying states of keratinocyte proliferation. Application of the Spearman rank coefficient of correlation revealed that the changes in mitotic activity of keratinocytes were unrelated either to the total density of leukocytes infiltrating the epidermis and dermis, or to the individual densities of the major phenotypic classes of inflammatory cells present. This makes it unlikely that the localized release of cytokines by infiltrating leukocytes is, by itself, the primary factor in the alteration in epidermal cell kinetics seen in ICD. Our results provide a further demonstration of the diverse actions of different chemical irritants on human skin and emphasize the need to regard ICD as a heterogeneous disorder.

Cell Division

Unilateral linear capillaritis.

We present four cases of a distinctive type of pigmented purpuric eruption occurring in a striking linear and pseudo-dermatomal distribution in young males. Whilst these cases share some of the clinical and histological features of other pigmented purpuric dermatoses, they are not readily classified with any of the entities so far defined in this group of disorders. We believe these cases represent a distinct group not previously described. Four patients with an unusual pigmented purpuric eruption are presented.

Adolescent

Selective expression of immune-associated surface antigens by keratinocytes in irritant contact dermatitis.

The expression of three immunoregulatory surface antigens by epidermal keratinocytes was studied in irritant contact dermatitis (ICD), in order to assess whether keratinocytes have a modulatory role in the pathogenesis of this disorder. Biopsies were taken from 48-h patch test reactions to six structurally unrelated irritants, and frozen sections immunolabeled with monoclonal antibodies to the major histocompatibility complex class II antigen, HLA-DR, intercellular adhesion molecule-1 (ICAM-1), and the 88-Kd glycoprotein CD36 (OKM5), as well as to the CD3 (T cells) and CD11a (lymphocyte function associated antigen-1, LFA-1) antigens. We found that there was very limited expression of HLA-DR by keratinocytes, with no correlation between the extent of HLA-DR positivity and the degree of T cell infiltration into the epidermis and dermis, suggesting that interferon gamma may not be a significant mediator of ICD at 48 h. In contrast, keratinocytes showed extensive upregulation of ICAM-1, with an excellent spatial association between ICAM-1 expression and LFA-1 positive leucocytes in the epidermis. This indicates that keratinocyte ICAM-1 induction is not restricted to diseases in which antigen presentation is pivotal, but that it has a generalized role in cutaneous inflammatory reactions, promoting the infiltration of leucocytes into the epidermis. Immunolabeling with OKM5 revealed that CD36 is present to a variable degree on keratinocytes in normal skin. Differential changes in the pattern of keratinocyte expression occurred between irritants, in a manner that suggested that the CD36 antigen does not act as an adhesion molecule in ICD, but rather that its expression is related to the proliferative state of the epidermis. The results of this study demonstrate that immune-associated antigens are selectively expressed on the surface of keratinocytes in 48-h ICD biopsies, implying that these cells play an important regulatory role in the development of the inflammatory response to irritant chemicals.

Antigens, Differentiation

Long-term survival and preservation of natural killer cell activity in a xeroderma pigmentosum patient with spontaneous regression and multiple deposits of malignant melanoma.

A 67-year-old man with xeroderma pigmentosum (XP) originally presented with malignant melanoma at the age of 28 years. This recurred 22 years later and subsequently numerous primary and secondary melanomas developed on the skin, several of which underwent spontaneous regression. Despite a marked lymphopenia, the proportion of natural killer cells was elevated and it is proposed that this led to the regression of the melanomas. Skin-derived fibroblasts from the patient were more sensitive to UVC (D10 approximately 3 J/m-2) than those from normal individuals (D10 approximately 15 J/m-2). The fibroblast culture was shown to be defective in excision repair with less than 10% of residual activity compared with controls. No assignment to a complementation group has yet been made. There was an elevated frequency of mutants resistant to 6-thioguanine in the circulating T lymphocytes.

Adult

Outcome after assisted ventilation in children with acquired immunodeficiency syndrome.

Twenty-two pediatric patients with AIDS required assisted ventilation during 27 pediatric ICU (PICU) admissions. Patients were retrospectively divided on the basis of whether they required assisted ventilation for acute respiratory failure (ARF) or for another reason. Sixteen (59%) courses of assisted ventilation were for ARF. The PICU mortality rate was 81% for the ARF group. Eleven (41%) courses of assisted ventilation were for reasons not involving ARF. The PICU mortality rate for the group without ARF was 9%, significantly lower (p less than .01) than for the ARF group. Pneumocystis carinii pneumonia (PCP) was documented during 48% of admissions. Occurrence of PCP did not affect mortality, nor was it more likely in those with than without ARF. Two patients with ARF survived to discharge from the hospital. Both died within 1 yr of ARF. Thus, the short-term prognosis for pediatric AIDS patients requiring assisted ventilation for ARF is extremely poor.

Acquired Immunodeficiency Syndrome

Differential effects of structurally unrelated chemical irritants on the density and morphology of epidermal CD1+ cells.

In order to gain a greater insight into the complex mechanisms of action of different irritant chemicals on the skin, we have studied the behavior of epidermal CD1+ cells in experimentally induced irritant contact dermatitis. Healthy, human volunteers were patch tested for 48 h with the following six chemically unrelated irritants and their appropriate vehicle controls; benzalkonium chloride, sodium lauryl sulphate, dithranol, nonanoic acid, croton oil, and propylene glycol. After visually assessing and grading the resulting inflammatory reactions, punch biopsies were taken and the morphology and density of CD1+ cells in the epidermis studied using immunocytochemical techniques in combination with image analysis and electron microscopy. Statistically significant decreases in the epidermal density of CD1+ cells occurred in the responses to dithranol (p less than 0.05) and nonanoic acid (p less than 0.01). Importantly, these changes in density were not simply due to variations in the intensity of inflammatory response (r = 0.1157). Alterations in the length of the dendritic processes of CD1+ cells were also induced, and semi-quantitative analysis revealed significant decreases in dendrite length in the reactions to sodium lauryl sulphate (p less than 0.05), nonanoic acid (p less than 0.001), croton oil (p less than 0.05), and dithranol (p less than 0.005). Unlike epidermal density, however, this effect on cell morphology was directly related to the severity of inflammation (r = -0.74, p less than 0.01). Morphologic evidence of cellular injury to Langerhans cells was seen by electron microscopy in the majority of biopsies, although relatively few cells were affected in sodium lauryl sulphate and propylene glycol reactions. Benzalkonium chloride, unlike the other irritants, also induced a state of metabolic activation in a high proportion of epidermal Langerhans cells. Lymphocyte/Langerhans cell apposition was observed in most samples, but was particularly prevalent in the reactions to dithranol. The results of this study demonstrate that significant changes in the morphology and density of Langerhans cells occur in irritant contact dermatitis, some of which are directly influenced by the chemical nature of the irritant.

Antigens, CD1

Angina bullosa haemorrhagica--a report of three cases and review of the literature.

Angina bullosa haemorrhagica (ABH) is a term that was first introduced by Badham in 1967 to describe a bullous disorder in which recurrent oral blood blisters appear in the absence of any identifiable systemic disorder. The aetiology of this condition remains obscure. Three cases are described, and their similarities and differences discussed. In one case the histopathology showed an intradermal blister; this feature has not previously been recorded for this condition.

Adult

Contact allergy to Bronopol.

A total of 8149 patients were patch tested with the preservative Bronopol in 7 European contact clinics. The majority of patients (6507) were investigated in London. Reactivity was low, with a total of 10 irritant (0.12%) and 38 allergic reactions (0.47%). In only 17 cases (0.21%) was the patch test reaction to Bronopol considered to be of current or past clinical relevance. Concomitant sensitization to formaldehyde was present in about 1/3 of patients. Based on these figures, the present sensitization rate to Bronopol in Europe seems to be quite low, which may be related to its less frequent use as a preservative in cosmetics and medicaments in comparison to parabens or isothiazolinones.

Adolescent

European multicenter study of TRUE Test, Panel 2.

Panel 2 of the standardized, ready-to-apply patch test, the TRUE Test, has been evaluated on 808 patients with suspected contact dermatitis. The patients were tested with 11 different allergens and the negative control, and compared with corresponding allergens in pet. (or aq.) in Finn Chambers fixed with Scanpor. The TRUE Test, Panel 2 and the control were applied symmetrically on the upper back. Left/right application of the respective test varied at random. Most tests were removed after 48 h and evaluated after 72 or 96 h, according to generally accepted recommendations. There were positive test reactions to all 11 allergens tested in the patient group. The concordance of positive reactions (1+, 2+, 3+) was 63% between TRUE Test, Panel 2 and the control method; 17% of positive reactions occurred only with TRUE Test, Panel 2 and 20% only with the compared method. Approximately 75% of all positive test reactions were explained by the patients' present or past history. Irritant/questionable reactions occurred in the same frequency for the 2 methods. Such reactions were recorded in less than 1% of all patches applied. No late reactions were recorded.

Allergens