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Biomedical subjects

A Kobza-Black

Publications and source records attributed to A Kobza-Black.

At least 19 recordsLinked to original sources

A clinical study of 23 cases of female anogenital carcinoma.

BACKGROUND: Vulval carcinoma is a relatively rare disorder that may have various aetiologies. Objectives To document the features and outcome in a series of patients with this disorder. METHODS: Retrospective analysis of patients presenting to a vulval clinic over a 5-year period. RESULTS: Twenty-one women presented with a squamous cell carcinoma (SCC) and two with a verrucous carcinoma (VC). The age range was 43-83 years. Twenty-one had well-established (1-30 years) vulval symptoms prior to developing their tumour. Specific tumour-related symptoms ranged from 3 weeks to 11 months. Eight had had a prior diagnosis of lichen sclerosus (LS) or lichen planus (LP), only two of whom were on regular treatment and follow-up. At presentation, 12 patients had clinical signs of LS, three of LP, and five had some changes of both LS and LP. Two patients had multifocal vulval intraepithelial neoplasia (VIN3). Only one had no evidence of any background vulval skin disease. The commonest histological changes noted in the epithelium either adjacent to or distant from the SCC were those of atrophic LS (n = 8), LS with squamous cell hyperplasia (n = 3), LS with hyperplastic foci and lichenoid infiltrate (n = 4), and LS with differentiated VIN3 (n = 1). Four cases demonstrated the changes of LP, and three showed VIN3. All patients were treated surgically and, in those who had lymphadenectomy, four had positive nodes. There have been two deaths due to metastatic disease, and one further patient has developed a second primary SCC at a different site. CONCLUSIONS: An underlying skin disorder prior to the development of their carcinoma was found in 22 of 23 patients with vulval SCC and is therefore an important risk factor.

Adult↗

The extent and nature of disability in different urticarial conditions.

Chronic forms of urticaria are common, often adversely impacting on quality of life. No formal studies have assessed the extent and nature of disability in different types of urticaria. The Dermatology Life Quality Index (DLQI) is a simple and validated 10-item questionnaire designed to measure and compare disability in different skin conditions. In this study, we aimed to assess the disability in different urticarial groups using the DLQI, allowing comparison with previously published DLQI scores in common skin diseases. The DLQI was administered to 170 consecutive patients attending a specialist urticaria clinic over a 4-month period. Consistent with previous studies using the DLQI, mean scores were not influenced by gender or age. Patients with chronic idiopathic urticaria without a concurrent physical urticaria (n = 47) suffered moderate quality of life impairment (mean +/- SD DLQI 25 +/- 24%). In comparison, patients with chronic idiopathic urticaria with concurrent delayed pressure urticaria (DPU) (n = 26) suffered significantly higher quality of life impairment (mean +/- SD DLQI 43 +/- 23%, 95% confidence interval for difference 7-29%). Disability in this group was greatest in the dimensions of work/study, symptoms/feelings and leisure. Subjects with another form of physical urticaria, cholinergic urticaria, also endured high levels of disability (n = 9, mean +/- SD DLQI 50 +/- 34%). From our urticaria study group, we have shown that subjects with DPU and cholinergic urticaria endure the most quality of life impairment. The mean DLQI scores demonstrated in these groups are comparable with those previously seen in severe atopic dermatitis out-patients (60%) and higher than those seen in out-patients with psoriasis (29.7%), acne (24.3%) and vitiligo (16.1%).

Activities of Daily Living↗

Dermal mast cell activation by autoantibodies against the high affinity IgE receptor in chronic urticaria.

Previous studies identified autoantibodies against the IgE high affinity receptor alpha-chain, Fc epsilon RI alpha, in sera of selected patients with severe chronic idiopathic urticaria. We have now determined the incidence of anti-Fc epsilon RI alpha autoantibodies in a group of 163 patients. Intradermal injection of autologous serum caused skin reactions indicative of mast cell degranulation in 98 (60%) patients. Based on histamine release from IgE-sensitized and nonsensitized basophil leukocytes of healthy donors, we detected anti-Fc epsilon RI alpha autoantibodies in sera from 38 (23%) urticaria patients and evidence for anti-IgE antibodies in a further nine patients. The sera that released histamine from basophils induced histamine release (4-34%, n = 12) from mast cells in incubated skin slices. Protein-G affinity chromatography of sera demonstrated that mast cell histamine release was IgG-mediated. Preincubation of sera or the IgG fraction with a recombinant alpha-chain of Fc epsilon RI inhibited histamine release from mast cells and basophils. Further studies with the mouse anti-human Fc epsilon RI alpha antibody 29C6 showed that mast cells and basophils were similarly sensitive to IgG-mediated direct cross-linking of Fc epsilon RI, with 0.01-1.0 micrograms/ml 29C6 evoking histamine release in each case. These studies demonstrate that circulating levels of anti-Fc epsilon RI alpha autoantibodies mediate histamine release from skin mast cells in vitro and, taken together with in vivo evidence of mast cell degranulation following intradermal injection of autologous serum, support the concept that anti-Fc epsilon RI alpha autoantibodies are relevant to the pathogenesis of severe chronic urticaria in about 25% of patients.

Adolescent↗

Immunohistological comparison of granulated cell proteins in induced immediate urticarial dermographism and delayed pressure urticaria lesions.

Urticarial dermographism and delayed pressure urticaria are two forms of physical urticaria which are well defined clinically and histologically. Previous studies have shown eosinophil granule protein deposition in urticarial reactions, including chronic urticaria, solar urticaria and delayed pressure urticaria. To evaluate and compare the involvement of granulated inflammatory cells in urticarial dermographism and delayed pressure urticaria, we studied sequential biopsies of induced lesions of urticarial dermographism and delayed pressure urticaria by indirect immunofluorescence, to detect eosinophil granule major basic protein (MBP) and neutrophil granule elastase. Biopsies from dermographic lesions at time 0, 5 min, 15 min, 2 h and 24 h, showed few infiltrating eosinophils, with minimal extracellular MBP deposition, and a few infiltrating neutrophils, with minimal neutrophil elastase deposition, throughout the evolution of the lesions. Sequential biopsies of delayed pressure urticaria at time 0, 20 min, 6, 12 and 24 h, showed eosinophil infiltration with extensive MBP deposition beginning at 20 min, and neutrophil infiltration with variable elastase deposition beginning at 20 min. Control tissue specimens from normal volunteers showed neutrophil infiltration and slight degranulation, but no eosinophil infiltration or degranulation. Comparison of urticarial dermographism with delayed pressure urticaria showed marked differences in the patterns of infiltration. Delayed pressure urticaria, with eosinophil and neutrophil degranulation, was strikingly similar to the IgE-mediated late phase reaction. In contrast, eosinophil and neutrophil involvement in urticarial dermographism was minimal. Considering the extent of eosinophil granule protein deposition and the biological activities of the eosinophil granule proteins, the findings in delayed pressure urticaria point to an important pathophysiological role of eosinophils in the disease.

Blood Proteins↗

Crusted scabies in pregnancy.

An otherwise healthy 19-year-old pregnant woman developed crusted scabies. She and her husband had previously been treated for scabies. In spite of appropriate treatment both suffered several relapses, and later their infant was also affected. Ultimately, the infection was eradicated. As far as we are aware, this is the first recorded case of crusted scabies occurring in a healthy pregnant woman.

Adult↗

Adult Still's disease.

Adult Still's disease (ASD) is a rare disorder of unknown aetiology, characterized by an evanescent, erythematous, maculopapular rash, fever, arthralgia, and a variety of systemic features. We report a case which illustrates the typical features of ASD, and manifests the hitherto unreported complication of diffuse cutaneous mucinosis.

Female↗

Increased interleukin 6, but reduced interleukin 1, in delayed pressure urticaria.

Interleukin 1 (IL-1) and interleukin 6 (IL-6) were measured by bioassays in suction-blister exudates from lesional skin, from skin immediately following a pressure challenge, and from control skin (not subjected to pressure) of patients with delayed pressure urticaria. IL-6 activity in lesional exudates was significantly higher than in exudates from the other two sites. IL-1 activity in lesional exudates was not significantly higher than in the control exudates, but significantly less IL-1 activity was found immediately after pressure challenge than from the control site.

Adult↗

Arachidonic acid transformation is not stimulated in delayed pressure urticaria.

Little is known about the molecular mechanisms or inflammatory mediators involved in delayed pressure urticaria (DPU). Pressure sufficient to provoke lesions was applied to the back of six patients with DPU. The levels of products of arachidonic acid transformation in skin exudate from the pressure challenged skin were estimated immediately after pressure was removed and 6 h later when lesions were present. These were compared to levels estimated in a similar way from unchallenged skin in these patients. Levels of leukotriene C4/D4/E4, prostaglandin E2, 12-hydroxyeicosatetraenoic acid and leukotriene B4 were not raised in lesional skin. Our results suggest that arachidonic acid metabolism is not stimulated in DPU.

Adult↗

Combined cold urticaria and cholinergic urticaria--clinical characterization and laboratory findings.

Thirteen patients with both cold and cholinergic urticaria are reported. There was considerable variability, particularly in the cold urticaria which was of the common cold contact type in seven patients, of the generalized cold induced cholinergic type in two and in four patients the lesions induced by direct contact with ice were morphologically like cholinergic urticaria, but appeared despite prior application of an acetyl choline antagonist. The natural history, laboratory findings and the effects of therapy are discussed.

Adolescent↗

Polycythaemia rubra vera and water-induced pruritus: blood histamine levels and cutaneous fibrinolytic activity before and after water challenge.

We studied blood histamine activity (HA) and cutaneous fibrinolytic activity (CFA) in a patient with polycythaemia rubra vera (PRV) and water-induced pruritus, before and after water exposure. The results suggest that the water-induced itching in PRV is associated with an increase in HA. In addition, markedly increased levels of CFA were found both before and after water exposure. These findings have been previously reported in patients with aquagenic pruritus (AP) but not in patients with PRV. As the water-induced itching in PRV and AP share many common features, these findings suggest that the pathophysiology of the water-induced pruritus in these two conditions may be similar.

Fibrinolysis↗

Prostaglandin D2 and histamine release in cold urticaria.

Prostaglandin (PG) D2 and histamine concentrations have been measured in blood draining cold-challenged forearm skin in patients with cold urticaria. Local venous concentrations of both histamine and PGD2 rose in four patients who developed a whealing response. Plasma histamine concentration increased from a mean resting value of 0.24 +/- 0.09 (SD) ng/ml to peak values of 16.9 to 96.6 ng/ml. Resting concentrations of PGD2 were below the limit of detection (5 pg/ml) in three patients and 62 and 27 pg/ml in the fourth. Peak plasma PGD2 concentration after challenge ranged from 166 to 279 pg/ml. Time course of histamine and PGD2 release was similar with peak concentrations at 6 and 10 minutes, respectively. The maximum clinical response occurred between 10 and 20 minutes after challenge. Our findings demonstrate that PGD2 is produced in association with mast cell degranulation in man, but the amount, relative to histamine, is low. Despite its high potency in production of inflammatory effects, PGD2 probably has only minor direct effects in cold urticaria, although it may act to potentiate other mediators.

Adolescent↗

Cholinergic urticaria with associated angio-oedema.

Three patients are described who developed angio-oedema and urticaria after a hot bath challenge and physical exercise. In one patient this was accompanied by a fall in peak expiratory flow rate. Blood levels of smooth muscle biological activity, measured using a bio-assay, increased in all patients after experimental challenge. The association of angio-oedema with cholinergic urticaria is emphasized and possible mechanisms discussed.

Adolescent↗

Elevated blood histamine levels and mast cell degranulation in solar urticaria.

1 Ultraviolet radiation (UVR)-induced wealing was studied in four patients with solar urticaria, whose measured action spectra were within the range 300 to 700 nm. 2 Elevated histamine levels were found in blood draining wealed skin in all four patients. 3 Histological and electron microscopial studies of the irradiated skin showed evidence of mast cell degranulation. 4 These findings demonstrate an association between histamine release from mast cells and wealing in solar urticaria, and should encourage evaluation of drugs which suppress histamine release in this disorder.

Adult↗