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Biomedical subjects

D J Eedy

Publications and source records attributed to D J Eedy.

At least 55 records · Page 3Linked to original sources

Distribution of interleukin 1 receptor antagonist protein (IRAP), interleukin 1 receptor, and interleukin 1 alpha in normal and psoriatic skin. Decreased expression of IRAP in psoriatic lesional epidermis.

The distribution of interleukin 1 alpha (IL-1 alpha), type 1 interleukin 1 receptor (IL-1R), and the interleukin 1 receptor antagonist protein (IRAP), was investigated in biopsies of normal skin, and in uninvolved and lesional skin of patients with psoriasis, using specific monoclonal antibodies. We report the novel finding that IRAP is distributed throughout the living layers of the epidermis in normal skin, and is also associated with sebaceous glands and eccrine sweat glands. Our finding that the inhibitor protein IRAP is present in areas where the pro-inflammatory cytokine IL-1 alpha is distributed provides strong evidence in favour of a cytokine regulatory system in normal skin. We further document for the first time that IL-1R in normal skin is localized to the living layers of the epidermis, sebaceous and eccrine glands, as well as to a prominent network of dermal dendritic cells, and upper dermal blood vessels. There was a consistent reduction in the level of IRAP expression in lesional compared with uninvolved skin in biopsies from six out of seven psoriasis patients. Decreased IRAP expression in lesions of psoriasis indicates that alterations in the level of this inhibitor protein may be important in the pathogenesis of inflammatory skin conditions.

Epidermis↗

Orthodontic headgear related to allergic contact dermatitis: a case report.

A case is reported of a 13-year-old girl who developed a facial rash shortly after orthodontic headgear was fitted. Patch testing revealed that she was strongly allergic to nickel and also allergic to cobalt and chrome. A diagnosis of allergic contact dermatitis was made. Painting the metal buckle of the cervical strap with polyurethane paint prevented further development of her rash, while allowing her orthodontic treatment to progress.

Adolescent↗

Neuropeptides of the primary sensory neurones in rat skin: an ontogenic study.

Cutaneous primary sensory neurones contain a number of biologically-active peptides, including substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP). However, little information is available on ontogenic changes in the tissue concentrations of these neuropeptides. In this study, the concentrations of these neuropeptides have been assessed in dorsal and ventral abdominal rat skin at various stages of development from foetal, early neonatal, late neonatal, weaner to adult, using sensitive and specific radioimmunoassays. In addition, the levels of peptide histidine isoleucine (PHI), a peptide found in non-sensory cutaneous nerves, were assessed to control the study. The levels of PHI and NKA immunoreactivity did not change significantly at any stage of development. However, the levels of SP and CGRP immunoreactivity were significantly elevated in the early neonate with CGRP remaining elevated in the late neonate. The levels of both SP and CGRP were not significantly different between other developmental groups. Significant elevations in cutaneous SP and CGRP concentrations in early neonatal life in the rat, at a time when the pups are blind and naked, may be related to control of cutaneous sensitivity, which during this period of development, has positive survival value for the pups.

Aging↗

Neuropeptides in psoriasis: an immunocytochemical and radioimmunoassay study.

The present study examines the presence of neuropeptides in the skin and plasma of patients with psoriasis using the techniques of immunocytochemistry and radioimmunoassay. Immunocytochemistry failed to demonstrate differences in the pattern of neuropeptide innervation in psoriatic lesional skin when compared to normal skin. However, radioimmunoassay of skin biopsy extracts, both substance P and vasoactive intestinal polypeptide, were significantly elevated in psoriatic lesional skin when compared with both psoriatic non-lesional and normal control skin (p less than 0.001). There was no significant difference between the plasma levels of neuropeptides in psoriatic patients compared to those of control subjects, and no significant correlation among the plasma levels of neuropeptides with the surface area of involvement with psoriasis. The finding of elevated levels of substance P and vasoactive intestinal polypeptide in lesional psoriatic skin suggests that these peptides may be involved in the pathogenesis or maintenance of the psoriatic skin lesion and the development of safe and stable antagonists of these neuropeptides may have applications in the treatment of psoriasis.

Adolescent↗

Minocycline-induced pigmentation occurring in two sisters.

Two sisters are described who developed facial pigmentation while on minocycline therapy for acne vulgaris. It is suggested that the possible mechanisms for this relatively uncommon complication occurring in these two patients may be due to either a genetically acquired alteration in metabolic handling of minocycline or to the ethinyloestradiol component of Dianette, which they were also receiving as treatment for their acne vulgaris. It is concluded that patients on minocycline should be regularly screened for signs of hyperpigmentation, especially if they are on other drugs which are known to accentuate pigmentation of skin.

Acne Vulgaris↗

Acromegaly and psoriasis.

A 56-year-old man with long-standing chronic plaque psoriasis was noted to be acromegalic. Investigations confirmed the presence of a large pituitary adenoma and following treatment of this by hypophysectomy his psoriasis cleared dramatically within 3 weeks.

Acromegaly↗

The nickel content of certain commercially available metallic patch test materials and its relevance in nickel-sensitive subjects.

The nickel contamination of the metallic patch test substances from 3 commercial sources was estimated by atomic absorption spectrophotometry. Contamination was generally greatest in the cobalt patch test substances. To determine whether the levels of contamination encountered were sufficient to produce a false positive patch test, 20 nickel-sensitive patients were patch tested to various concentrations of free elemental nickel in aqueous solution. The level of nickel contamination was less than that required to produce a false positive patch test in our patients, but was at a level which could produce false positive reactions in subjects highly sensitive to nickel.

Adolescent↗

A possible role for superoxide production in the pathogenesis of contact dermatitis.

Superoxide generation by blood monocytes was examined in patients with irritant, nickel, and chromate hand dermatitis. Phorbol myristate acetate stimulated monocytes generated significantly more superoxide in patients with nickel dermatitis, as did patients with hand eczema generally. No significant stimulation of monocyte superoxide generation occurred with either opsonized zymosan or PMA in the presence of excess superoxide dismutase in any of the groups of hand dermatitis. The results indicate a biochemical stimulation of superoxide which may accentuate the immunological damage in the skin that is observed in nickel and perhaps chromate dermatitis.

Adolescent↗

Elevated T cell subpopulations in dental students.

The absolute numbers of circulating white cells and lymphocyte subpopulations were studied in 25 final-year dental students and compared with a control group of 28 medical students. The total lymphocyte count, total T cell numbers (CD3), T helper/inducer (CD4), and T suppressor/cytotoxic (CD8) numbers were significantly elevated in the dental students as compared with the control group. There was no significant difference in the T helper/inducer to T suppressor/cytotoxic cell ratios or the circulating B cell (CD21) and natural killer cell (CD16) numbers between the study and control groups. Patch testing to mercury and mercuric compounds in both the study and control groups showed no evidence of cutaneous hypersensitivity to mercury. The reason for the observed elevations in T cell subpopulations in dental students is not clear. However, one possible explanation is the dental student's occupational exposure to mercury. Further work is underway to examine this possible relationship and it is suggested that dental personnel take adequate measures to reduce their exposure to mercury until the results of these studies are available.

Adult↗

Characterisation of xenopsin immunoreactivity derived from pepsinised human skin and possible mechanism of in vivo generation.

Human skin was subjected to a variety of extraction and enzymatic digestion procedures. Extracts and digests were subjected to neurotensin and xenopsin radioimmunoassays of known specificity. No neurotensin immunoreactivity was detected in any preparation with any region-specific antiserum. C-terminal xenopsin immunoreactivity was present in skin homogenates following incubation with both soluble and solid-phase pepsin and in those incubated with a leucocyte lysate or purified cathepsin D. The generation of xenopsin immunoreactivity was dependent on low pH and enzymes of pepsin-type specificity acting on a tissue precursor of approximately 30 kDa. Gel permeation chromatography of skin-derived xenopsin immunoreactivity identified a single molecular species larger than synthetic xenopsin which was resolved into two components by reverse-phase HPLC with retention times similar to synthetic xenopsin and kinetensin. Human skin thus contains a high-molecular-weight precursor protein and an endogenous acid protease, cathepsin D, capable of generating a peptide of similar size and C-terminal structure to amphibian xenopsin under acidic conditions such as might occur locally in wounds or at sites of inflammation.

Chromatography, Gel↗

Vasoactive intestinal peptide (VIP) and peptide histidine methionine (PHM) in human eccrine sweat glands: demonstration of innervation, specific binding sites and presence in secretions.

Vasoactive intestinal peptide (VIP) and peptide histidine methionine (PHM) immunoreactivities have been detected in alcohol extracts of human axillary skin using sensitive and specific radioimmunoassays. VIP immunoreactivity (7.63 + 2.33 pmol/g, x + SE, n = 9) was more abundant than PHM immunoreactivity (3.86 + 0.56 pmol/g, x + SE, n = 9). Immunocytochemistry of sections of skin revealed a network of VIP/PHM immunoreactive nerve fibres around the perimeter of eccrine but not apocrine sweat glands. In vitro autoradiography of skin sections using 125I-labelled VIP and PHM, demonstrated binding sites on the membranes of eccrine gland secretory cells. The binding of each radiolabelled ligand was eliminated by the presence of a large molar excess of appropriate cold peptide but was unaffected when incubated with related peptide, indicating the presence of specific binding sites for both VIP and PHM. Radioimmunoassay of Sep-pak concentrated human sweat identified the presence of both VIP immunoreactivity (30.6 pmol/l) and PHM immunoreactivity (43.4 pmol/l). Reverse-phase HPLC analysis of axillary skin extracts and sweat, followed by radioimmunoassay of fractions, identified single resolved peaks of VIP and PHM immunoreactivity with identical retention times to synthetic standards. Eccrine sweat glands in human axillary skin have VIP and PHM peptidergic innervation and possess specific binding sites for each peptide which are both secreted to the surface of the skin.

Binding Sites↗

Beta-adrenergic stimulation of cyclic AMP is defective in cultured dermal fibroblasts of psoriatic subjects.

Epidermal cells from psoriatic lesions demonstrate a very low cAMP response to beta-adrenergic stimuli. We have shown that a similar abnormality occurs in dermal fibroblasts from affected areas of skin. The cells, after 5-12 passages in tissue culture, had a much reduced response to 10(-8) M and 10(-6) M isoproterenol when compared with fibroblasts from control subjects. The abnormality was not abolished by the addition of the phosphodiesterase inhibitor, 3-isobutyl-I-methylxanthine. Other putative agonists tested were vasoactive intestinal peptide and peptide histidine methionine. Neither of these had an effect on dermal fibroblasts from either normal controls or from lesions of psoriasis.

1-Methyl-3-isobutylxanthine↗

Anaphylactic reactions to topical antibiotic combinations.

We describe two patients who developed anaphylaxis type reactions following the application of the topical antibiotic Polyfax (polymixin B and bacitracin). We draw attention to this potentially serious complication of topical antibiotic preparations and emphasize the need for careful history taking before prescribing such preparations.

Aged↗

Irritant contact facial dermatitis due to nebulizer therapy.

A case is reported of a patient with long-standing, severe airflow obstruction requiring long-term nebulizer therapy developing a facial dermatitis in the area bounded by the nebulizer mask. The facial dermatitis seems to be the result of the combined irritancy of the nebulizer solutions and moisture, and prophylactic measures are suggested for patients requiring long-term nebulizer therapy.

Atropine Derivatives↗

Diabetic ketoacidosis in a district general hospital, 1981-1986.

The outcome of therapy of poorly controlled insulin-requiring cases of diabetes mellitus needing admission to a district general hospital from 1981 to 1986 was examined. There were 156 admissions to the hospital, 17 of these classified as severe diabetic ketoacidosis (serum standard bicarbonate less than 14 mmol/l). A 'low dose' insulin regimen was used in each case of severe ketoacidosis. No patient who was admitted died within a six-month period. These figures emphasise the value of a policy of direct hospital admission for poorly controlled diabetics and suggest that early diagnosis in general practice is vital to allow the application of relatively simple and standard hospital treatment.

Adult↗

Thirteen-year retrospective study of Bowen's disease in Northern Ireland.

In a retrospective study we measured the incidence of internal malignancy in patients diagnosed as having Bowen's disease, in Northern Ireland, between 1970 and 1983. Data on 157 patients were obtained from hospital notes, death certificates, the Northern Ireland Cancer Registry and the patients' general practitioners. There was a preponderance of females with Bowen's disease with a female to male ratio of 2.8:1. The incidence of internal malignancy was significantly greater in patients with Bowen's disease than that expected for the general population, suggesting that these patients should be screened for occult malignancy. Patients with multiple areas of Bowen's disease did not appear to be more at risk of internal malignancy than those with a single lesion.

Adult↗