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The phospholipid PAF-acether is released from a range of inflammatory cell types and, in experimental animals, has properties appropriate to a mediator of inflammation. We have studied the inflammatory characteristics of intradermally injected PAF-acether in human skin. An early weal and flare response was succeeded, in a proportion of subjects, by an area of late-onset erythema at the site of the resolved weal, reminiscent of the dual response to allergen in sensitized individuals. The time-course and dose-response relationship of the early response has been determined and a synergistic interaction between PAF-acether and prostaglandin E2 established. PAF-acether should therefore be considered as a potential mediator of both acute and persisting inflammation in man.

Polyethylene glycol (PEG) was used as a probe molecule to investigate intestinal absorption in eight patients with eczema and evidence of food allergy and ten with eczema alone. In both groups absorption of molecules of larger molecular weight was greater than in normal subjects but absorption of molecules of low molecular weight was normal. There was no difference in absorption between eczema patients with or without food allergy. These results suggest that there is an intestinal mucosal defect in eczema which exists whether or not there is coexistent food allergy. Half the patients with eczema alone and two of the eight with food allergy had more of the large molecular weight PEG recovered in their urine in the second 12 h after ingestion than in the first 12 h. This could be the result of abnormal permeability in the more distal small bowel or even in the colon.

Impaired beta-adrenergic and enhanced alpha-adrenergic reactivity have been implicated in the pathogenesis of atopic dermatitis. We have measured the elevation of cyclic AMP in peripheral blood leukocytes in response to isoprenaline, histamine and prostaglandin E2, in the presence and absence of a phosphodiesterase inhibitor. An impaired response to beta-adrenergic stimulation was demonstrated in subjects with atopic dermatitis but impaired responses were also observed with histamine and prostaglandin E2. In vivo, both noradrenaline and salbutamol caused significant inhibition of the histamine-induced weal response in atopic and normal subjects. However, there was no significant difference between the two groups when alpha- and beta-adrenoceptor responses were compared.

The ultrastructure of the human mucocutaneous end organ is described. The corpuscle is divided into sublobular units comprising axon terminals surrounded by generally concentric lamellar processes which are derived from laminar cells whose nuclei are situated towards the periphery of the sublobules. Interlamellar substance which contains elastic tissue, collagen and coarse periodicity crossbanded structures intervenes between lamellar processes. Specialized zones of contact resembling desmosomes are found at intervals seemingly connecting adjacent lamellar processes and axons with lamellar processes. The ultrastructural features of this end organ are similar to that of the Meissner corpuscle despite minor differences of the light microscopical appearance, which supports the view that differences in sensory end organs are merely variations on a common organizational basis.

The histopathological appearance of proliferative squamous lesions removed from the skin of iatrogenically immunosuppressed patients differs subtly from that of classical malignant and premalignant epidermal lesions. The majority of cases show 'Bowenoid' changes with a marked degree of cellular atypia including characteristic multinucleate cells.

The effects of the sequential stages of paraffin wax embedding on immunolabelling of cutaneous cell membrane antigens by monoclonal antibodies are described. Modifications in incubation times for fixation, dehydration, clearing and wax embedding of sections were examined. Labelling of the cell surface antigens deteriorates only after formal saline fixation for a period longer than 4 hr. Dehydration in ethanol had a minor adverse influence but clearing in xylene diminished immunoreactivity markedly. Both deleterious effects could be circumvented by conducting the procedures at 4 degrees C. The wax embedding procedure at 58 degrees C adversely affected labelling after 1 hr.

Platelet activating factor (Paf-acether, AGEPC) is a family of ether-linked phospholipids known to be released from a range of inflammatory cell types. In vitro and in experimental animals, it seems to be a mediator of inflammation, and intradermal injection of Paf-acether in man elicits a biphasic inflammatory response, reminiscent of the dual response to allergen in sensitized individuals. In the present study, cutaneous histology was assessed in sequential skin biopsies from six normal volunteers after intradermal injection of 200 or 800 pmol Paf-acether. Paf-acether (200 pmol) induced intravascular accumulation of neutrophils, accompanied by a perivascular mixed cellular infiltrate which was composed predominantly of neutrophils at 4 and 12 hours, and lymphocytes and histiocytes at 24 hours. Control injections of lyso-Paf and normal saline induced no noteworthy histological changes. Paf-acether (800 pmol) resulted in vessel destruction, gross endothelial swelling and a perivascular infiltrate of mononuclear cells and neutrophils, accompanied by occasional evidence of leucocytoclasis. By virtue of its ability to induce inflammatory cell accumulation in human skin, Paf-acether should be considered as a potential mediator of inflammatory disorders such as psoriasis.

The clinical and histopathological features of nineteen cases of Zoon's balanitis and a comparable lesion of the vulva have been reviewed. The condition is particularly distinguished by characteristic histological changes affecting the epidermis and the dermal vasculature. The presence of a plasma cell infiltrate is relatively non-specific. Recognition of these features should allow simple differentiation from premalignant, infective and other inflammatory penile lesions which may be more responsive to treatment.

A new method has been used to measure tissue levels of amiodarone and its major metabolite desethylamiodarone. Amiodarone-pigmented skin has a drug and metabolite concentration ten times that of non-pigmented skin. Iodine-rich amiodarone and its metabolite have been detected in secondary lysosomes by energy dispersive analysis of X-rays. Amiodarone induces a phototoxic reaction with an action spectrum in both the UV-B and UV-A wavelengths.

The light, polarization and electron microscopic changes in the liver of four cases of erythropoietic protoporphyria (EPP) are described. In one of these cases liver involvement resulted in death, whereas in the other three there were no symptoms of referable to hepatic disease. In two cases hepatic pigment was readily visible on light and polarization microscopy and corresponded to characteristic crystalline aggregates seen ultrastructurally. Pronounced micronodular cirrhosis and cholestasis were present in the fatal case, while in the other only mild periportal fibrosis and mononuclear inflammatory cell infiltrate occurred. The third and fourth cases showed no evidence of hepatic involvement on light microscopy. Electron microscopy, however, revealed characteristic crystal-containing vacuoles indicative of protoporphyrin deposition. The need for early detection of the hepatic lesion is emphasized.