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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
PubMed2005

Thyroid autoimmunity in chronic urticaria.

BACKGROUND: Chronic urticaria (CU) is an autoimmune process in some patients. An association between CU and autoimmune thyroid disease has also previously been proposed. Our group has identified functionally significant histamine-releasing autoantibodies in one subset of CU patients (subset 1), predicted by positive autologous intradermal serum tests and positive histamine release from donor basophil leucocytes in vitro. Sera from a second subset of patients (subset 2), all of whom had positive autologous intradermal serum tests, failed to release histamine from donor basophils. A final disease subset (subset 3) has no identifiable skin reactivity (negative autologous serum skin test) or in vitro histamine releasing activity. OBJECTIVES: In order to examine further the possible relationships between thyroid autoimmunity, thyroid dysfunction and CU, we have examined thyroid autoantibodies and thyroid-stimulating hormone (TSH) levels (an indirect measure of thyroid dysfunction) in the three CU subsets. PATIENTS/METHODS: We studied 182 patients (69% female), of whom 90 had a positive autologous intradermal serum test. RESULTS: Eighteen skin test-positive and four skin test-negative patients had thyroid microsomal antibodies (TMA). TSH outside the normal range was found in 13 skin test-positive and one skin test-negative patient. These findings represent clustering of TMA positivity [risk ratio (RR) 4.06, 95% confidence interval (CI) 1.56-10.6] and of abnormal thyroid function (RR 15.5, CI 2.07-11.6) among the skin test-positive patients. However, in the overall study group an elevated TSH was present in seven patients (3.8%, CI 1.6-7.8) comparable to the 5% expected prevalence in the community. Thyroglobulin antibodies (TGA) were present in two of 182 patients. CONCLUSIONS: There were significant differences between skin test-positive and skin test-negative patients with regard to autoimmune thyroid disease. Evidence for autoimmune thyroid disease and abnormal thyroid function was largely found among the skin test-positive patients, supporting the theory of an autoimmune aetiology in this group.

Adolescent↗
PubMed2002

An audit of the use of self-administered adrenaline syringes in patients with angio-oedema.

BACKGROUND: Self-administered adrenaline syringes may be prescribed for patients at risk of life-threatening episodes of angio-oedema or anaphylaxis. OBJECTIVES: To determine whether patients are able to use these syringes appropriately and adequately. METHODS: Twenty-nine consecutive patients who had been prescribed self-administered adrenaline syringes for severe angio-oedema were recruited. All completed a questionnaire (unsupervised), and were asked to demonstrate how to use a dummy syringe. RESULTS: Three of 29 (10%) patients had been prescribed syringes in the absence of severe angio-oedema or collapse. Seventeen of 29 (59%) patients had been prescribed two syringes, and 21 of 29 (72%) kept a syringe with them at all times. Twenty of 28 (71%) patients had had the use of a syringe demonstrated to them with the initial prescription, but two of 29 (7%) had never been shown how to use it. Only six of 26 (23%) patients had been told to telephone for an ambulance after using a syringe. Only seven of 29 (24%) patients would use a syringe for an episode of collapse, whereas eight of 28 (29%) would use one for an episode of lip swelling. Nine of 21 (43%) patients had not been warned about adverse effects, although 13 of 20 (65%) given adrenaline had had at least one adverse effect. Of the 25 patients asked to demonstrate their use of a syringe, only 14 (56%) were able to perform all steps correctly, and three (12%) were unable to perform any of the steps. Despite this, all 29 patients felt confident about giving themselves an injection, and most felt more secure having been prescribed syringes. CONCLUSIONS: As self-administered adrenaline syringes are prescribed for life-threatening events, it is vital that they are given to appropriate patients with adequate written instructions and proper demonstration at the time of the initial prescription. As a result of this study we have developed a more detailed patient information leaflet, and all patients are shown how to use a syringe for a second time when attending the clinic for follow-up.

Adolescent↗
PubMed2000

Randomized double-blind study of cyclosporin in chronic 'idiopathic' urticaria.

BACKGROUND: Histamine-releasing activity (HRA) is detectable in up to 50% of patients with chronic ordinary urticaria. OBJECTIVES: To determine the effect of cyclosporin on clinical features and HRA in patients with chronic urticaria. METHODS: Thirty patients with severe unremitting disease, responding poorly to antihistamines and showing a positive autologous serum skin test (ASST) as a marker of HRA, were randomized to 4 mg kg-1 daily of cyclosporin (Sandimmun, n = 20) or placebo (n = 10) for 4 weeks. Non-responders were offered open-label cyclosporin for 4 weeks. All were followed for up to 20 weeks or until clinical relapse; all took cetirizine 20 mg daily throughout the study. The primary measure of efficacy was a daily urticaria activity score (UAS) of weal numbers and itch (maximum score 42 per week). A positive response was defined as a reduction to < 25% of baseline weekly UAS and relapse as a return to > 75%. The effect of cyclosporin on serum HRA was assessed by in vitro basophil histamine release assays and ASSTs before and after treatment. RESULTS: Twenty-nine patients (19 active, 10 controls) completed the randomized trial medication. Eight of 19 on active treatment but none on placebo had responded at 4 weeks (P < 0.05). Three others on active drug met the criterion for response at 2 weeks but not at 4 weeks. Mean reduction in UAS between weeks 0 and 4 was 12.7 (95% confidence interval, CI 6.6-18.8) for active and 2.3 (95% CI - 3.3-7.9) for placebo (P = 0.005). Seventeen non-responders (seven randomized to active and 10 to placebo) chose open-label cyclosporin and 11 responded after 4 weeks. Six of the eight randomized active drug responders relapsed within 6 weeks. Of the 19 responders to randomized and open-label cyclosporin, five (26%) had not relapsed by the study end-point. Mean in vitro serum HRA fell from 36% (95% CI 22-49%) to 5% (95% CI 1-8%) after cyclosporin treatment (n = 11, P < 0.0001). The ASST response to post-treatment serum was also reduced (P < 0.05). CONCLUSIONS: This study shows that cyclosporin is effective for chronic urticaria and provides further evidence for a role of histamine-releasing autoantibodies in the pathogenesis of this chronic 'idiopathic' disease.

Adult↗
PubMed1999

The autologous serum skin test: a screening test for autoantibodies in chronic idiopathic urticaria.

One-third of patients with chronic idiopathic urticaria (CIU) have circulating functional autoantibodies against the high affinity IgE receptor FcepsilonRI, or IgE. The intradermal injection of autologous serum causes a weal and flare reaction in many patients with CIU, and this reaction forms the basis of the autologous serum skin test (ASST). We have determined the parameters of the ASST which define the optimal sensitivity and specificity for the identification of patients with autoantibodies. Two physicians (R.A. S. and C.E.H.G.) performed ASSTs in a total of 155 patients with CIU, 40 healthy control subjects, 15 patients with dermographism, nine with cholinergic urticaria and 10 with atopic eczema. Patients were classified as having functional autoantibodies by demonstrating in vitro serum-evoked histamine release from the basophils of two healthy donors. There were significant differences (P < 0.001) in the mean weal diameter, weal volume, weal redness and flare area of the intradermal serum-induced cutaneous responses at 30 min between patients with CIU with autoantibodies and either those without autoantibodies or control subjects. The optimum combined sensitivity and specificity of the ASST was obtained if a positive test was defined as a red serum-induced weal with a diameter of >/= 1.5 mm than the saline-induced response at 30 min. For R.A.S. and C.E.H.G., the ASST sensitivity was 65% and 71% and specificity was 81% and 78%, respectively. Using these criteria, the following subjects had positive ASSTs: none of 15 dermographics, none of 10 atopics, one of nine cholinergics and one of 40 controls.

Autoantibodies↗
PubMed1999

Human leucocyte antigen class II associations in chronic idiopathic urticaria.

The major histocompatibility complex (MHC) acts as a marker for self during T-cell ontogeny and is associated with the pathogenesis of many autoimmune diseases. Recent investigations have shown about 30% of patients with chronic idiopathic urticaria (CIU) have IgG autoantibodies against the high-affinity IgE receptor, FcepsilonRI, or IgE. A link between MHC class II alleles and CIU has not been reported previously. DNA was extracted from blood of 100 Caucasian patients with CIU, and the MHC class II type determined using the polymerase chain reaction with sequence-specific primers, testing for DRB and DQB1 alleles. The frequency of alleles in CIU patients was compared with that found in 603 controls. Further human leucocyte antigen (HLA) typing on patient subsets, classified by the patients' responses to intradermal injection of autologous serum and their serum-induced histamine release from basophil leucocytes of healthy donors, was undertaken. HLA DRB1*04 (DR4) and its associated allele, DQB1*0302 (DQ8), are raised in CIU patients compared with a control population (P = 2 x 10-5 and P = 2 x 10-4, respectively). HLA DRB1*15 (DR15) and its associated allele, DQB1*06 (DQ6), are significantly less frequently associated with CIU. The HLA DRB1*04 association is particularly strong (corrected P = 3.6 x 10-6) for patients whose serum has in vivo and in vitro histamine-releasing activity. HLA class II typing is consistent with the concept that CIU is a heterogeneous disease, and supports an autoimmune pathogenesis in a subset of patients.

Adolescent↗
PubMed1999

Rowell's syndrome.

Rowell's syndrome is the name given to a distinct group of patients with lupus erythematosus who develop erythema multiforme-like lesions and have a characteristic serological picture. We report a case of a 29-year-old woman of Afro-Caribbean origin who presented with an erythema multiforme-like eruption on the hands. Subsequently she developed painful erythematous swellings on the feet and scaly plaques on the forearm and thigh consistent with subacute cutaneous lupus. She developed a positive antinuclear factor and had positive anti-Ro and anti-La antibodies and a positive rheumatoid factor. All of these features are consistent with Rowell's syndrome which we believe is a rare but distinct variant of cutaneous lupus erythematosus.

Adult↗
PubMed1998

Scombrotoxic fish poisoning.

We report the case of a 30-year-old patient who developed scombrotoxic fish poisoning after eating cooked fresh tuna. Symptoms included a bright red rash, tightness of the chest, palpitations, anxiety, mild headache and dizziness, all of which resolved spontaneously within 2-3 h. Such poisoning results from the consumption of spoiled fish of the families Scomberesocidae or Scombridae - in particular tuna, mackerel, skipjack and bonito - which contain high levels of histidine. Incorrect storage of fish allows bacterial histidine decarboxylase to convert histidine to histamine. The ensuing symptoms are thought to result from the ingestion of histamine. Scombrotoxic fish poisoning is preventable by the correct handling and refrigeration of these fish.

Adult↗
PubMed1995

Mast cells and T lymphocytes in chronic urticaria.

Mast cells are considered to be the primary effector cells in urticaria but it is possible that lymphocytes contribute to the formation of weals by secreting histamine releasing factors. The aim of this study was to examine the population of mast cells and to quantify the T cell subsets and their activation status in delayed pressure urticaria (DPU), chronic idiopathic urticaria and normal controls. Three biopsies were obtained from each of four patients with chronic idiopathic urticaria but not DPU. Three biopsies were taken from each of 13 patients with DPU, from a combination of unchallenged skin and at 0, 2, 6, 24, 48, and 120 h after weighted steel rods (diameter 1.5 cm) had been applied to the thighs. Three biopsies were similarly obtained from each of four normal controls before an identical pressure challenge and at 6, 24 and 48 h afterwards. The chloracetate esterase stain was used to demonstrate mast cells and an alkaline phosphatase anti-alkaline phosphatase immunohistochemical technique to assess the phenotypic and activation characteristics of the T cell infiltrate. The mast cell count did not differ significantly between unchallenged skin from DPU patients and normal controls. Following a pressure challenge to the DPU patients, the number of stainable mast cells decreased significantly to a level comparable with that in spontaneous weals of chronic idiopathic urticaria. Investigation of T cell subsets showed a preponderance of CD4+ cells over CD8+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Platelet activating factor (PAF) and lyso-PAF in psoriasis.

Previous studies have shown that scale from lesional psoriatic skin contains substantial amounts of platelet activating factor (PAF). In this study, PAF and its immediate precursor, lyso-PAF, were measured in exudates from abrasions on lesional and uninvolved psoriatic skin, and from skin of healthy subjects. The mean amounts of PAF recovered from lesional and uninvolved psoriatic skin (n = 13) and from healthy skin (n = 14) were not significantly different (range 0.05-2.14 pmol/sample). Mean recoveries of lyso-PAF from lesional psoriatic skin (n = 9) and skin of healthy subjects (n = 13) were also similar (9.5 +/- 1.9 and 11.0 +/- 1.9 pmol/sample, respectively), but significantly less lyso-PAF was found in exudates from the uninvolved psoriatic skin (n = 9; 3.1 +/- 0.4 pmol/sample; P < 0.01 relative to both lesional psoriasis and healthy skin). The finding of reduced lyso-PAF in uninvolved psoriatic skin was unexpected because increased phospholipase-A2 activity is associated with psoriasis. These results do not support the hypothesis that extracellular PAF contributes significantly to the inflammation associated with psoriasis.

Adolescent↗
PubMed1993

Platelet activating factor, lyso-platelet activating factor and arachidonic acid release in normal human skin and the influence of topical steroid treatment.

1. Previous, in vitro, studies have established the synthesis of platelet activating factor (PAF) by the 're-modelling' pathways in which the activation of a phospholipase A2 (PLA2) enzyme catalyses the hydrolysis of an ether-acyl-phosphocholine to give concomitant release of lyso-PAF, the immediate precursor of PAF, and arachidonic acid, the precursor of the icosanoids. The aim of this study was to investigate the relationship between PAF and eicosanoid release in human skin, and to study the effect of treatment of skin with a topical steroid, on the release of PAF, lyso-PAF and arachidonic acid. 2. A novel assay procedure was developed for the simultaneous assay of PAF and lyso-PAF in skin exudates from abrasions and suction blisters in normal human skin. In addition we assayed arachidonic acid and prostaglandin E2 (PGE2), a representative eicosanoid. 3. The mean amounts of mediator recovered in the first 30 min period following abrasion were PAF 0.43, lyso-PAF 11.9, PGE2 25.7 and arachidonic acid 760 pmol/sample. The molar ratio of PAF:lyso-PAF:arachidonic acid in skin exudates from abrasions was 1:30:1800 and in suction blister exudates was 1:90:3660. 4. Time course studies showed a decline in the recoveries of arachidonic acid and lyso-PAF, of about 50% in 2 h. In contrast, PAF was recovered in exudates at a constant rate over 2 h but PGE2 release decreased by more than 90% after the initial 30 min period. 5. Topical application under occlusion, of 0.05% clobetasol propionate, a potent corticosteroid, significantly reduced lyso-PAF by 30% in suction blister exudates but did not significantly alter the concentrations of PAF or arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1992

H1 antagonists in the management of the itch of urticarias.

This article reviews the effect of H1 antihistamines on the pruritus of urticaria, from articles in which their therapeutic effect on chronic idiopathic and physical urticaria is assessed. In limited studies available pruritus improved concomitantly with wealing by an average of two thirds, though the response in individual patients was variable. In some physical urticarias the pruritus and wealing showed disproportionate improvement compared to erythema. The minimally sedating H1 antihistamines were as effective or more effective than classical H1 antihistamines. The dose of antihistamines that totally abolished a histamine weal only partly reduced urticarial weals (therefore by inference also of the associated pruritus). Additional therapy aimed at pruritogenic mediators other than histamine would be expected to improve urticarial pruritus.

Histamine H1 Antagonists↗
PubMed1991

Immediate-pressure urticaria--a distinct disorder.

We report a patient who has an immediate wealing response to pressure in the absence of symptomatic dermographism, which we designate 'immediate-pressure urticaria'. Our patient also suffered from cholinergic urticaria and chronic idiopathic urticaria in the past, demonstrating the clustering of urticarias which frequently occurs.

Female↗
PubMed1989

A timed study of the histopathology, direct immunofluorescence and ultrastructural findings in idiopathic cold-contact urticaria over a 24-h period.

The histopathology, immunofluorescence and ultrastructure of skin in idiopathic cold-contact urticaria have been studied over the 24 h following the application of a cold stimulus sufficient to provoke a confluent weal on the anterior thigh. Biopsies were taken 10 min, 2 h and 24 h after ice removal. Considerable epidermal and dermal oedema was present. Type I and Type II mast-cell degranulation was noted but was not universal. Lymphatics and capillaries were dilated and endothelial cells showed an increase in micropinocytotic activity, without evident vasculitis. In two cases packed platelets were seen within vessel lumina. There was no change in the infiltrating dermal cell population and direct immunofluorescence was negative. The evidence suggests that idiopathic cold-contact urticaria is an exudative rather than an infiltrative process.

Adolescent↗
PubMed1988

Prostaglandin D2 and histamine release in cold urticaria unaccompanied by evidence of platelet activation.

Six patients with acquired primary cold urticaria and six normal control subjects were challenged with a 5-minute immersion of an arm in cold water, at 10 degrees C, to induce cold urticaria. Venous blood draining the arm was sampled before and at 5 and 20 minutes after challenge. Prostaglandin D2 levels in the serum increased significantly after cold challenge but did not correlate with the severity of the urticaria. Significant elevations in histamine after cold challenge tended to be higher in the patients with a low threshold to cold reaction. Two markers of platelet activation, platelet factor 4 and beta-thromboglobulin, remained at basal levels 5 minutes and 20 minutes after challenge.

Adult↗