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Biomedical subjects

C B Archer

Publications and source records attributed to C B Archer.

At least 19 recordsLinked to original sources
PubMed1998

The intradermal effects of the H3 receptor agonist R alpha methylhistamine in human skin.

We have investigated the possible existence of the H3 histamine receptor in human skin with the highly selective ligands R alpha methylhistamine (RAMHA) (H3 agonist) and thioperamide (H3 antagonist). We compared the intradermal effects of RAMHA with histamine, and studied their potential modulation by the H1 antagonist terfenadine, and H2 antagonist cimetidine. The effects of RAMHA and thioperamide on codeine phosphate-, substance P- and histamine-induced weal and flare responses were also studied. RAMHA produced dose-related weal and flare responses that were approximately 10- and fivefold less, respectively, than responses to histamine. Flare responses to RAMHA were significantly inhibited by oral terfenadine (P < 0.05). Weal and flare responses to histamine after oral cimetidine showed much intersubject variation, and cimetidine did not significantly alter either RAMHA- or histamine-induced weal and flare responses. Codeine phosphate-, substance P- and histamine-induced responses were not significantly affected by concurrent administration of RAMHA. Thioperamide was not found to influence codeine phosphate-, substance P-, RAMHA- or histamine-induced effects. RAMHA induces vascular (weal and flare) responses in human skin, and these responses are partially inhibited by terfenadine. There is a trend for RAMHA to have an additive effect to the weal induced by substance P and histamine, although our results largely do not reach statistical significance. Thioperamide does not affect the vascular responses to RAMHA, codeine phosphate, histamine or substance P. We cannot conclude that the effects of RAMHA are induced by H3 receptors on cutaneous endothelial or mast cells.

Adult↗
PubMed1997

Long-term efficacy and safety of cyclosporin in severe adult atopic dermatitis.

A prospective, open, multicentre study was performed to investigate the efficacy and safety of long-term treatment with cyclosporin in adults with severe atopic dermatitis. Subjects were treated for a maximum of 48 weeks. For the first 8 weeks, cyclosporin was administered at 2.5 mg/kg per day. The dose was then adjusted according to response. Disease activity was monitored using the six-area, six-sign score and the proportion of skin involved. Pruritus and sleep disturbance were assessed using four-point scales. Response was further evaluated on a five-point scale. Adverse events, blood pressure and serum biochemistry were monitored. Tolerability was assessed on a five-point scale. One hundred subjects were enrolled and 65 completed 48 weeks of treatment. Withdrawals occurred due to remission (three), inadequate response (seven), protocol violations (11) and adverse events (14, of which seven were probably treatment related). Cyclosporin produced rapid and highly significant improvements in all indices of disease activity. Sixty-five subjects considered that they had shown a considerable improvement or complete clearance of disease. Most patients relapsed after cessation of treatment, but neither signs nor symptoms had returned to baseline severity 8 weeks later. Blood pressure and serum creatinine levels increased slightly, and in one subject renal impairment was a major factor contributing to withdrawal of the drug. Overall, 85 subjects rated the tolerability of cyclosporin as good or very good. The results indicate that cyclosporin has a place in the long-term treatment of severe atopic dermatitis provided that appropriate patients are selected and careful monitoring is performed.

Adolescent↗
PubMed1997

Urinary leukotriene E4 levels in patients with atopic dermatitis.

Leukotriene synthesis may be increased in a variety of inflammatory diseases. Urinary leukotriene E4 is a stable metabolite of leukotrienes C4 and D4 which has previously been found to be increased in exacerbations of severe asthma and after antigen inhalation. Levels of urinary LTE4 in seven patients during and after a severe flare of atopic dermatitis were measured by high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA). Mean urinary LTE4 levels (+/- SEM) were not increased during (16.7 +/- 3.7 pg/mumol) or after (16.9 +/- 4.8 mumol) the acute exacerbation of atopic dermatitis when compared with the normal range (mean = 23.8 [95% confidence interval 19.9-28.2] pg/mumol creatinine). These findings do not provide evidence of cysteine leukotriene involvement in the pathogenesis of atopic dermatitis.

Acute Disease↗
PubMed1997

The effects of topical doxepin on responses to histamine, substance P and prostaglandin E2 in human skin.

The tricyclic antidepressant, doxepin, is known to have H1 and H2 antihistaminic effects. Recently, 5% doxepin cream has been marketed in the U.S.A. for treatment of eczematous dermatoses. We investigated the effects of topical doxepin treatment on histamine-, substance P- and prostaglandin E2- (PGE2) induced responses in the skin of normal and atopic subjects. We compared the effects of topical doxepin with those of the oral antihistamine terfenadine. The weal volume and flare area responses to histamine were significantly reduced by treatment with topical doxepin or oral terfenadine in both normal and atopic subjects (P < 0.05). The mean +/- SEM percentage reduction in flare area for 10 micrograms/site of histamine in non-atopics and atopics was 48 +/- 8% and 60 +/- 17% with terfenadine, and 54 +/- 12% and 81 +/- 4% with topical doxepin, respectively. The mean percentage reduction in weal volume for the same dose of histamine in non-atopics and atopics was 70 +/- 9% and 63 +/- 16% with terfenadine, and 96 +/- 2% and 89 +/- 6% with topical doxepin, respectively. The flare but not the weal response to substance P was inhibited by both treatments in all subjects (P < 0.05). The mean +/- SEM percentage reduction in flare area for 200 pmol/site of substance P in non-atopics and atopics was 53 +/- 10% and 73 +/- 4% with terfenadine, and 74 +/- 7% and 75 +/- 4% with topical doxepin, respectively. The cutaneous responses to PGE2 were not affected by either drug. The inhibitory effects of doxepin were as great as those of terfenadine, and doxepin had a significantly greater effect than terfenadine in inhibiting the weal response to histamine and flare response to substance P in normal volunteers (P < 0.05). There was no significant difference between atopics and non-atopics in the percentage reduction of cutaneous responses by oral terfenadine or topical doxepin. Marked sedation occurred in three of the first 10 subjects treated with topical doxepin, necessitating a reduction in dosage for the remaining six subjects. In summary, topical doxepin was as effective as, and sometimes more effective than, a standard dose of oral terfenadine in the inhibition of histamine-induced and axon-reflex-mediated cutaneous responses. The marked sedative effect may limit its clinical use in some patients.

Administration, Topical↗
PubMed1996

Effects of H1- and H2-antihistamines on platelet-activating factor and bradykinin-induced inflammatory responses in human skin.

Previous studies show that oral antihistamines affect the weal and flare response to intradermal injections of the inflammatory mediators platelet-activating factor (PAF) and bradykinin (BK). The aim of this study was to compare the effects of terfenadine (an H1-antagonist) and cimetidine (an H2-antagonist) on weal and flare responses to PAF and BK in healthy non-atopic human volunteers. The effects of doxepin on PAF responses were investigated, as there is evidence that doxepin may have direct anti-PAF effects in addition to its known antihistaminic actions. Terfenadine significantly reduced weal and flare responses to PAF (mean reduction 53 and 73%, respectively) and flare responses to BK (mean reduction 78%) but had no effect on weal responses to BK. Doxepin significantly reduced both weal and flare responses to PAF (mean reduction 43 and 68%, respectively, at higher doses of PAF). Cimetidine had no effect on weal or flare responses to PAF or BK. These findings suggest that the flare response to intradermal BK is mediated via histamine release while the weal response is not. The effects of the various antagonists of PAF-induced responses suggest that its effects too may be mediated via histamine, the similarity of the effects of terfenadine and doxepin on these responses indicating that the effects of doxepin may be due to its known antihistamine activity rather than to any specific PAF-antagonistic properties. Platelet-activating factor (PAF) is a phospholipid which is released from a wide range of cell types and also from vascular endothelium. PAF is formed by the conversion of ether-linked phospholipids initially to the biologically inactive lyso-PAF and then by acetylation to PAF. Intradermal injection of PAF in human skin causes vasodilatation and increased vascular permeability, producing a weal and flare response with accompanying pruritus. Bradykinin (BK) is a vasoactive polypeptide formed by the action of enzymes known as kallikreins on inactive precursors called kininogens. Its effects include an increase in blood flow and vascular permeability and stimulation of the release of prostaglandins and histamine. On intradermal injection in human skin it causes a weal and flare response with associated pain rather than pruritus. Previous studies have suggested that the weal and flare response to PAF may be mediated in part by histamine release. Given that BK is known to cause histamine release it appears possible that the responses to both compounds may be modified by conventional antihistamines. Experiments based on this premise have found that antihistamines have a pronounced effect on the flare response to PAF but a less marked effect on weal responses. The weal response to BK was unaffected by systemic antihistamines but studies have produced conflicting results with regard to effects on the flare response. The aim of this study was to compare the effects of terfenadine (an H1-antagonist) and cimetidine (an H2-antagonist) on PAF- and BK-induced weal and flare responses in healthy, non-atopic human volunteers. Based on the treatment of cold urticaria it has been suggested that doxepin, which has known H1- and H2-antagonistic effects, may in addition show specific anti-PAF activity. We compared the effects of doxepin on PAF-induced intradermal responses with those of terfenadine and cimetidine in this study.

Administration, Oral↗
PubMed1996

Comparison of the actions of kallidin and bradykinin in the skin of normal and psoriatic subjects.

With the recent development of selective drugs acting on the kinin system and the identification of a kallikrein-like enzyme from psoriatic blister fluid, there is now much interest in the possible role of kinins in psoriasis. We have examined the time-course of the inflammatory (weal and flare) responses to intradermal kallidin (lysbradykinin) and bradykinin in normal volunteers, and have compared the dose-response effect of these agents in normal volunteers and patients with psoriasis. Initially, normal subjects (n = 5) received coded intradermal injections of 50 microliters normal saline containing kallidin or bradykinin (0.1, 0.5, 1.0 and 5.0 micrograms). Weal volume, weal area and flare area were calculated at 5, 15, 30 and 60 min by measuring two perpendicular diameters and change in skinfold thickness. Weal and flare measurements were subsequently made at 15 and 5 min, respectively. Patients with psoriasis (n = 9) and normal subjects (n = 10) were given intradermal injections of kallidin (0.1 and 1.0 microgram) and bradykinin (0.1, 0.5 and 1.0 microgram) in clinically normal forearm skin, using histamine and normal saline as controls. The dose-response effects of kallidin on weal and flare responses in human skin were established in the study and compared with those of bradykinin. There was wide inter-individual variability for both agents and, although mean responses to the highest doses of kallidin and bradykinin were decreased in psoriatic skin, no significant differences were found between the psoriatic and normal group for kallidin, bradykinin or histamine. Hence, there do not appear to be any obvious altered vascular responses to kallidin or bradykinin in patients with psoriasis, despite the fact that kinins may be generated in psoriatic tissue.

Adult↗
PubMed1996

Minocycline-induced discolouration of the sclerae.

We report two patients with minocycline-induced pigmentation of the sclerae. Cutaneous pigmentation is a well-recognized complication of minocycline therapy, but only five cases of pigmentation of the sclerae have been described previously. These five patients have a number of features in common with the two reported here. We propose that these patients represent the most severe end of the spectrum of minocycline-induced cutaneous changes. Patients should be warned about the possibility of the occurrence of pigmentary changes before starting therapy.

Aged↗
PubMed1994

The U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis. I. Derivation of a minimum set of discriminators for atopic dermatitis.

A working party of 13 dermatologists, two family practitioners and a paediatrician was assembled, with the aim of developing a minimum list of reliable discriminators for atopic dermatitis. Each physician was asked to select 10 consecutive new cases of unequivocal mild to moderate atopic dermatitis and 10 controls with other inflammatory dermatoses. Each subject was examined by two independent observers, who were blind to the clinical diagnosis and study aim, with regard to 31 clinically useful diagnostic features for atopic dermatitis. Two hundred and twenty-four patients were studied (120 cases and 102 controls). Using the key physician's clinical diagnosis as a gold standard, the sensitivity and specificity of each of the 31 diagnostic criteria were tested. Using multiple logistic regression techniques, a minimum set of diagnostic criteria for atopic dermatitis was derived. These were: history of flexural involvement, history of a dry skin, onset under the age of 2, personal history of asthma, history of a pruritic skin condition, and visible flexural dermatitis. Adjustment for age, sex, region, social class and ethnic group did not alter the choice of final criteria. The discriminatory value of these criteria was also satisfactory when tested against a further sample of 150 patients drawn from the community, who did not have skin disease.

Adolescent↗
PubMed1993

Erythema elevatum diutinum associated with Wegener's granulomatosis and IgA paraproteinemia.

A 69-year-old man had erythema elevatum diutinum for several years before he developed IgA paraproteinemia and a limited form of Wegener's granulomatosis. This is the first report of an association between erythema elevatum diutinum and Wegener's granulomatosis. IgA paraproteinemia has been reported in association with erythema elevatum diutinum but not with Wegener's granulomatosis.

Aged↗
PubMed1993

Giant primary mucinous sweat gland carcinoma of the scalp.

Primary mucinous sweat gland carcinoma is a rare tumour which usually behaves in a relatively benign manner. This is illustrated by the massive proportions which this tumour reached in the case described, without evidence of metastases.

Adenocarcinoma, Mucinous↗
PubMed1992

Diagnosis of lichen planus pemphigoides in the absence of bullae on normal-appearing skin.

A case of lichen planus pemphigoides is described in which bullae and erosions affected the areas of lichen planus only. The diagnosis was confirmed by the finding of linear C3 and IgG deposition in the basement membrane zone (BMZ) of perilesional skin. Indirect immunofluorescence revealed circulating IgG anti-BMZ antibodies and a lamina lucida split was demonstrated by electron microscopy. This case challenges the clinical dogma that the occurrence of bullae on normal-appearing skin is essential for the diagnosis of lichen planus pemphigoides.

Humans↗
PubMed1990

Platelet activating factor-induced clinical and histopathologic responses in atopic skin and their modification by the platelet activating factor antagonist BN52063.

The clinical and histopathologic responses to intradermal platelet-activating factor (PAF-acether) in atopic subjects, without evidence of atopic dermatitis are documented. An immediate acute wheal and flare reaction was observed in all volunteers. Histopathologically, the reaction was characterized by a predominantly neutrophilic response, which was seen at 30 minutes and was maximal at 4 hours. Eosinophils were observed in the infiltrate as early as 30 minutes after injection, and were maximal by 12 hours. The specific PAF-acether antagonist BN52063 antagonized the acute flare response to intradermal PAF-acether but had little effect on cellular recruitment at the site of injection.

Adult↗
PubMed1990

Subcutaneous xanthomatosis.

A patient with multiple subcutaneous xanthomata in whom there were only minor abnormalities of the fasting serum lipid profile is described. To our knowledge, this is only the second published case of subcutaneous xanthomatosis.

Aged↗
PubMed1989

Kaposi's sarcoma in a homosexual--10 years on.

Kaposi's sarcoma is seen in one of several clinical settings. Before the recognition of the acquired immune deficiency syndrome (AIDS) in the early 1980s, the most frequent presentation of Kaposi's sarcoma in the UK was the so-called 'classical' form of the disease. The most common form of Kaposi's sarcoma in this country is now that associated with AIDS, which particularly affects young male homosexuals. Here we describe a homosexual man who has developed many Kaposi's sarcoma tumours during the past 10 years. The disease has run a benign course and there is no evidence of infection with human immunodeficiency virus (HIV).

Acquired Immunodeficiency Syndrome↗