Topical glycopyrrolate should not be overlooked in treatment of focal hyperhidrosis.
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Biomedical subjects
Publications and source records attributed to G M Kavanagh.
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BACKGROUND: Lithium carbonate is the most widely used long-term treatment for bipolar affective disorders, but its ability to trigger and exacerbate psoriasis can become a major problem in patients for whom lithium is the only treatment option. Inositol depletion underlies the action of lithium in bipolar affective disorders and there are good theoretical reasons why the use of inositol supplements might be expected to help this group of patients. OBJECTIVES: To determine whether inositol supplements improve the psoriasis of patients on lithium therapy. METHODS: Fifteen patients with psoriasis, who were taking lithium, took part in a randomized, double-blind, placebo-controlled, crossover clinical trial comparing the effect of inositol supplements with those of a placebo (lactose). Changes in the severity of their psoriasis were measured by Psoriasis Area and Severity Index scores recorded before and after the different courses of treatment. The effect of inositol supplements on the psoriasis of 11 patients who were not taking lithium was evaluated in the same way. RESULTS: The inositol supplements had a significantly beneficial effect on the psoriasis of patients taking lithium. No such effect was detected on the psoriasis of patients not on lithium. CONCLUSIONS: The use of inositol supplements is worth considering for patients with intractable psoriasis who need to continue to take lithium for bipolar affective disorders.
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We report two patients with severe palmar hyperhidrosis who responded to BOTOX delivered not by injection, the usual method of delivery, but by iontophoresis. The Botulinum molecule has been considered too large for delivery into the skin this way. However, other large peptides, both non-ionic and cationic, have been delivered successfully by this method, so we suspected that BOTOX could in fact be iontophoresed. Our saline-controlled treatment of these two patients with a small iontophoresis unit (Iomed Phoresor II) allowed small volumes of standard BOTOX dilutions to be used, and demonstrates that iontophoresis can indeed deliver BOTOX successfully. This has important therapeutic potential for the large number of patients with focal hyperhidrosis. They may be spared painful injections, and in more severe cases, invasive surgery.
The aim of this study was to compare the efficacy and tolerability of twice-daily vs. once-daily regimes of dithranol (anthralin) in Lassar's paste. Over a 4-year period, 61 inpatients with stable plaque psoriasis gave informed consent and entered a randomized controlled trial, having twice or once-daily application of dithranol in Lassar's paste as part of otherwise standard Ingram's regime. Primary outcome measurements were time required in hospital, nursing time, changes in total body surface area affected by psoriasis and thickness of a target plaque and in some patients, an assessment of the recurrence of psoriasis. Doctors were blinded as to the regime being used. At entry, mean patient age, lesional surface area and target plaque thickness were comparable in both groups and no patient had received systemic therapy in the preceding 3 months. Forty-two patients completed the study, two (11%) in the twice-daily group withdrawing due to skin irritation or 'burning'. Mean lesional surface area and target plaque thickness were similar in both groups at hospital discharge. Mean (+/- SD) time spent in hospital was not significantly different in each group, being 13.3 (+/- 6.2) days and 13.9 (+/- 4.5) days for the twice-daily and once-daily groups, respectively (P = 0.36). Duration of hospitalization did not correlate with surface area or plaque thickness on admission. Mean (+/- SD) nursing time spent on treatment was significantly greater in the twice-daily group, at 0.82 (+/- 0.33) hours per day compared with 0.51(+/- 0.25) hours per day in the once-daily group. Relapse rate at 6 months was not different between the two groups.
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Heat-set gels and aggregates from beta-lactoglobulin (beta-Lg), one of the major globular proteins from milk, have been studied on a molecular distance scale using negative-staining transmission electron microscopy (TEM), wide-angle X-ray diffraction (WAXD), and Fourier transform infrared spectroscopy (FTIR). The microscopy showed long linear aggregates forming in solutions at pH 2 (and sometimes 2.5) after prolonged heating. While there appeared to be no differences in aggregates formed under these conditions in H(2)O as compared with D(2)O, at all other pH and pD values, and in the presence of added salt, much shorter linear aggregates were formed. These became slightly more extended the further the pH was removed from pI. Wide-angle X-ray diffraction (WAXD) showed a diffuse beta-sheet halo at 2θ=19 degrees in patterns for both dried native and aggregated protein (irrespective of pH) with only a small change (sharpening) of this feature on heat treatment. Solution FTIR spectra, measured at pD=2, 2.5, 3, and 7, during heating, indicated shoulder development at 1612 cm(-1) in the carbonyl-stretching Amide I region diagnostic of a modest increase in intermolecular beta-sheet. In terms of the shoulder size, no distinctions could be made between acid and neutral aggregate structures. At all pHs, beta-lactoglobulin showed only limited secondary and tertiary structural changes in aggregation, in contrast to previous studies of insulin aggregation, where highly ordered crystalline fibrils were indicated. The current work has implications both in structural studies of food biopolymers and in ongoing studies of pathological protein self-assembly in disease states, such as spongiform encephalopathies.
We report two patients who satisfied the diagnostic criteria for actinic reticuloid (AR) on initial presentation, in whom genotypic analysis of early skin biopsies failed to show T-cell gene receptor rearrangements. Both patients progressed to widespread skin involvement associated with histopathological and genotypic features of mycosis fungoides (MF). Arguably, these patients may have had photosensitive MF from the outset, but their clinical features, phototesting, and subsequent demonstration of a T-cell gene receptor rearrangement in the skin could also suggest progression of AR to MF.
Cryosurgery is an alternative treatment option to surgical excision for lentigo maligna. Clinical evidence of recurrence is usually characterized by repigmentation at the treated site. We report two patients who developed amelanotic malignant melanoma following cryosurgery for a pigmented lentigo maligna. These cases illustrate the potential risk of treating lentigo maligna with cryosurgery.
From the Scottish Melanoma Group database for south-east Scotland we evaluated 5-year follow-up in patients with cutaneous malignant melanoma excised between 1979 and 1994 and devised an 'evidence-based' review protocol. Of the 1568 with stage I melanoma, 293 (19%) developed a recurrence, 32 had a second primary melanoma and 97 had an in-situ melanoma. The disease-free interval shortened progressively with increasing tumour thickness. Overall, 80% of recurrences were within the first 3 years, but a few patients (< 8%) had recurrences 5 or 10 years after the initial surgery. In-situ melanomas did not recur. Almost half (47%) the recurrences were noted first by the patient, and only 26% were detected first at a follow-up clinic. One hundred and thirty-nine patients (89%) were still under review when their recurrences were detected, and 102 (65%) had been seen within the previous 3 months. Questionnaires were completed by 120 patients: sun protection and avoidance, and mole examination were more likely after melanoma excision. We recommend 3-monthly review of patients with invasive lesions for the first 3 years. Thereafter, those with lesions >/= 1.0 mm need two further annual reviews. Patients with in-situ lesions should be reviewed once, to confirm adequate excision (0.5 cm margins) and to give appropriate education. Surveillance beyond 5 years is only justified if there are special risk factors.
Weal volume and flare area responses to intradermal platelet activating factor (PAF) and histamine, both in the presence and absence of the protein carrier, human serum albumin (HSA), were measured in the skin of normal subjects, atopics without dermatitis, and in the normal-appearing skin of patients with atopic dermatitis. The ultrastructural effects of intradermal PAF were also studied in the same groups of subjects. Weal and flare dose-responses to PAF were enhanced by the presence of human serum albumin, HSA itself producing a significantly greater mean weal response in each group than lyso-PAF (P < 0.01). However, comparison of normal subjects, atopics without dermatitis and patients with atopic dermatitis, showed the differences in dose-response effects of PAF and histamine on weal volume and flare area to be nonsignificant. The cellular response to PAF in normal subjects and atopics consisted predominantly of neutrophil extravasation; eosinophils were noted in the normal-appearing skin of atopics and patients with atopic dermatitis 30 min and 4 h after injection. At an ultrastructural level PAF induced opening of endothelial gaps and extravasation of neutrophils in each group.
Aneurysmal fibrous histiocytoma (AFH) (Santa-Cruz DJ, Kyriakos M. Aneurysmal ('Angiomatoid') fibrous histiocytoma of the skin. Cancer 1981;47:2053-2061) is a distinct but poorly recognized clinicopathological variant of cutaneous fibrous histiocytoma (CFH) that may result from the slow extravasation of blood into the tumour. The resulting lesion can have a very different clinicopathological appearance resulting in diagnostic confusion. We describe a patient with an AFH that presented as a pigmented nodule on the foot and discuss clinical recognition and histological differentiation from other tumours.
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.
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We have examined 14 of 28 members of a four-generation family, 10 of whom demonstrated the clinical features of the scleroatrophic syndrome of Huriez, a cancer-prone dermatosis. Several members of this family demonstrated additional features, previously unrecorded in this syndrome, including poikiloderma-like changes on the nose, flexion contractures of the little finger, a distinctive little finger nodule, and telangiectasia on the lips. Genetic linkage was excluded to distal chromosome 4q (LOD score-4.399 at theta = 0.001). This concurs with the recent reappraisal study of one of the two original families described by Huriez, in which no evidence of linkage between this syndrome and the MNSs erythrocytic system (mapped to 4q28-q31) was found. This is the first report of a family from the U.K. with this syndrome.
We report two cases of the trigeminal trophic syndrome, complicating peripheral and central interruption of the trigeminal sensory pathways. These cases illustrate the diagnostic and management problems that this syndrome presents.
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The effect of dithranol on superoxide generation in vivo has not been studied previously. Neutrophils produce large amounts of superoxide following stimulation by phorbol 12-myristate-13-acetate (PMA). We studied the effect of dithranol on PMA-activated superoxide generation by isolated neutrophils from normal subjects, and measured whole blood luminescence in response to PMA, using samples from 13 psoriatic patients before and during dithranol treatment. Oxidized dithranol had no effect on the PMA-stimulated superoxide generation in neutrophils, but there was a modest dose-related increase in superoxide generation by neutrophils exposed to dithranol before activation. Similar results were found with neutrophils obtained from the 13 psoriasis patients. Three of these patients suffered a dithranol burn and developed a neutrophilia, with a marked increase in stimulated superoxide generating ability. Our findings suggest that dithranol treatment of a psoriasis plaque is associated with a decrease in oxygen radical generating capacity in vivo. However, where inflammation of perilesional and uninvolved skin occurs, neutrophils appear to become semi-activated or primed.