Search PubMed⌕ Search

Biomedical subjects

T Zuberbier

Publications and source records attributed to T Zuberbier.

At least 73 records · Page 4Linked to original sources
PubMed1998

Differential effects of new-generation H1-receptor antagonists in pruritic dermatoses.

In search of an improved treatment of pruritic dermatoses, we have studied azelastine, a novel H1-receptor antagonist, during a 2-week treatment period, using a double-blind, placebo-controlled design. The potent H1-antagonist cetirizine was used for comparison. Symptoms were recorded daily by the patients on a diary card, using a 4-point scale. The same parameters and adverse events were evaluated at weekly intervals, and global improvement was evaluated at the end of treatment. In all 230 evaluable patients with moderate to severe itching, azelastine caused an overall significant improvement in comparison to placebo (P = 0.02), with significance also for pruritus (P = 0.01 after 1 week and P = 0.02 after 2 weeks). Both drugs reduced itching more effectively in urticaria than in atopic eczema. Azelastine was superior to cetirizine in reducing pruritus, whereas cetirizine caused a more marked reduction of whealing. Both drugs rarely caused fatigue and dry mouth, but taste perversion occurred only in azelastine-treated patients (9.7%) and headaches only with cetirizine (10.4%). Therefore, the two H1-blockers exert differential effects on pruritus verses whealing and a distinctive adverse events pattern. The data also underline the low efficacy of antihistamines in atopic eczema, compared to urticaria.

Adolescent↗
PubMed1998

Most chronic urticaria is food-dependent, and not idiopathic.

Although chronic urticaria is generally thought to be mostly idiopathic, we have recently provided convincing evidence that in the majority of patients, food ingredients provoke the symptoms and sustain the disease. On a diet largely avoiding preservatives, dyes and natural pseudoallergens, 73% of patients experienced remission of more than 6 months duration, starting within the first 3 weeks after initiation of the diet. This response rate is clearly higher than the reported 24% spontaneous remission rate over the same time period. The specificity of the dietary effect was proven 1) by double-blind provocation with pureed pseudoallergen-low versus -rich food and 2) by induction of a clinical response to a 3-week diet low in pseudoallergens, but not to a standard diabetes diet in 3 patients studied in a double-blind crossover design. On double-blind, placebo controlled oral provocation, only 18% of diet-responsive patients reacted to known food preservatives and dyes, but 71% to pureed tomatoes and 44% to their steam extracts. These findings identify naturally occurring pseudoallergens in food as major elicitors of chronic urticaria. In contrast, autoantibodies against Fc epsilonRIalpha have been identified in only about 30% of chronic urticaria patients, and evidence for their truly causative role is still lacking since therapeutic measures work in patients irrespective of the presence or absence of the autoantibodies. For both food intolerance and Fc epsilonRIalpha-autoantibodies in chronic urticaria, the associated pathomechanisms are however still in need of clarification. Meanwhile, the diet-responsiveness in the majority of patients opens new perspectives for the management of chronic urticaria.

Animals↗
PubMed1997

C3a and C5a stimulate chemotaxis of human mast cells.

The factors that control migration of mast cells to sites of inflammation and tissue repair remain largely undefined. Whereas several recent studies have described chemotactic factors that induce migration of murine mast cells, only stem cell factor (SCF) is known to induce migration of human mast cells. We report here that the anaphylatoxins C3a and C5a are chemotactic factors for the human mast cell line HMC-1, human cord blood-derived mast cells (CBMC) and cutaneous mast cells in vitro. The presence of an extracellular matrix protein, laminin, was required for chemotaxis in response to complement peptides. Migration of mast cells towards C3a and C5a was dose-dependent, peaking at 1 microg/mL (100 nmol/L), and was inhibited by specific antibodies. Pretreatment with pertussis toxin inhibited the anaphylatoxin-mediated migration of HMC-1 cells, indicating that Gi proteins are involved in complement-activated signal transduction pathways in human mast cells. Both C3a and C5a also induced a rapid and transient mobilization of intracellular free calcium ([Ca2+]i) in HMC-1 cells. Besides SCF, other chemotactic factors tested, such as interleukin-3, nerve growth factor, transforming growth factor beta, RANTES (regulated upon activation, normal Tcell expressed and secreted), monocyte chemotactic protein-1 (MCP-1), MCP-2, MCP-3, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta, failed to stimulate migration of human mast cells. In summary, these findings indicate that C3a and C5a serve as chemotaxins for human mast cells. Anaphylatoxin-mediated recruitment of mast cells might play an important role in hypersensitivity and inflammatory processes.

Calcium↗
PubMed1997

Enhanced P-selectin expression in chronic and dermographic urticaria.

In both chronic and dermographic urticaria, superficial perivascular leukocytic infiltrations are seen histologically in lesional skin. We have therefore investigated the role of endothelial adhesion molecule expression in these diseases. E-selectin, P-selectin, ICAM-1 and VCAM-1 expression was examined immunohistologically, and the serum levels of the soluble forms of these adhesion molecules were determined by EIA in patients with chronic urticaria, dermographic urticaria as well as in healthy controls (n = 8 in each group) and subjects with symptomatic allergic rhinitis (n = 7) for comparison. A significant increase (p<0.01) was observed for soluble P-selectin in dermographic urticaria (mean 487+/-44 ng/ml) and chronic urticaria (mean 464+/-74 ng/ml) compared to healthy controls (mean 149+/-15 ng/ml) and rhinitis subjects (mean 177+/-30 ng/ml). In contrast, the other adhesion molecules were not significantly elevated in both urticaria groups. Immunohistologically, a strong expression of P-selectin was found in superficial vessels of lesional and nonlesional skin in dermographic urticaria with only a mild increase of the other adhesion molecules studied, supporting the findings observed with the soluble forms in the patients' sera. Since an alteration of soluble P-selectin was not seen in symptomatic allergic rhinitis, an unspecific effect due to inflammation appears to be unlikely. These results therefore point to a potentially relevant role of the endothelial P-selectin expression in the evolution of urticarial whealing.

Case-Control Studies↗
PubMed1996

[Epidemiology and clinical aspects of cold urticaria].

To study the frequency and clinical aspects of cold urticaria in Central Europe, patient data from a university dermatology clinic and a private dermatology office between 1984-94 were analysed and the patients re-examined if possible. The incidence of cold urticaria was found to be 0.05%. Of the 56 patients with cold urticaria (31 women, 25 men), 49 had idiopathic cold urticaria. The mean age was 41.0 +/- 15.6 year, the mean duration of disease 7.9 +/- 5.8 years. Atopy was found in 46.5% of patients, and 23.2% of the patients suffered from other types of urticaria (cholinergic, chronic idiopathic, dermographic, aquagenic and heat-induced). Laboratory examinations were only rarely abnormal. 44 patients were treated with antihistamines, with generally only moderate symptomatic improvement. Treatment with antibiotics (penicillin, 1-2 mil IU/d over 2-4 weeks, n = 18, or tetracyclines, 2 g/d over 2 weeks, n = 10) induced full remission in 13 patients and symptomatic improvement in 8. During an average of 6.5 year-follow-up, 20 of 43 symptomatic patients went into spontaneous remission. The good therapeutic response to antibiotics in this study underlines the need for a better elucidation of the cause of cold urticaria, in view of possible infectious causes.

Adolescent↗
PubMed1996

Histamine releasability of basophils and skin mast cells in chronic urticaria.

In order to clarify the pathogenetic role of basophils and mast cells in chronic urticaria, histamine and leukotriene (LT)C4 release was examined in washed mixed leukocytes (n = 8) and skin mast cells (n = 5) from patients with chronic urticaria and compared with the same cells from normal controls (n = 9). Anti-IgE-stimulated basophil histamine release was significantly reduced in urticaria patients (median 2.9% vs 15.1% in normal controls), whereas histamine release to A23187, FMLP, and PAF, as well as anti-IgE-induced LTC4 release, showed no differences in both groups. In contrast, anti-IgE-stimulated skin mast cells from urticaria patients reacted similarly to those of controls (median histamine release 11.4% vs 14.2% in normal controls). Pretreatment of the cells with interleukin (IL)-3 upregulated responsiveness of basophil histamine release to anti-IgE in urticaria patients (median histamine release 14.3%), but pretreatment with the H2-antagonist cimetidine showed no effect. These data show that reduced basophil histamine releasability in chronic urticaria is not H2 mediated. It is a stimulus-, mediator-, and cell type-restricted phenomenon that can, at least partially, be reversed in the presence of the cytokine IL-3.

Adult↗
PubMed1996

Allergic sensitization to native and heated celery root in pollen-sensitive patients investigated by skin test and IgE binding.

The rates of sensitization and allergy to four birch pollen related plant foods were investigated in a group of 167 patients who were sensitive to at least one kind of pollen and one particular food. Sensitivity was concluded from a positive skin prick test or the determination of specific IgE, whereas allergy was based on anamnestic data. The positivity rates for sensitization and allergy, respectively, were: apple, 93 and 84%; hazelnut, 90 and 78%; celery, 70 and 14%; carrot, 60 and 37%. Comparative testing by skin prick test and enzyme allergosorbent test (EAST) with extract from native and microwaved (750 W, 30 min, 100 degrees C) celery root was performed on 46 of these patients. At least one positive test result (either prick test or EAST) was obtained for native celery in 36/46 (78%) and for heated celery in 20/46 (43%) of these patients. Although the concordance between the EAST and the skin test was very low, extended control experiments of both test procedures revealed no evidence for nonspecificity. Immunoblot analyses of extract from native celery and sera of 60 patients with a positive EAST (class > or = 2, > or = 0.7 U/ml) for celery resulted in the following rates of IgE binding to known cross-reactive celery allergens: Api g 1:33%, celery profilin: 17%; multiple bands most probably due to carbohydrate epitopes: 32%. The rate of binding to other allergens was below 10%. Since these three important structures are also present in birch pollen, no allergen could be identified as a candidate to mediate an exclusive celery/mugwort association. Investigation of extract from native and heated celery by immunoblotting pointed to a high lability of Api g 1, whereas profilin and carbohydrate epitopes appeared to be more resistant to heat. It has been concluded that sensitization to celery in German patients is without clinical significance in the majority of cases, in contrast to other birch-pollen-related plant foods such as apple and hazelnut. For the particular kind of extract used, neither the EAST nor the skin test alone represents an appropriate diagnostic method for testing sensitization to celery.

Allergens↗
PubMed1996

Double-blind crossover study of high-dose cetirizine in cholinergic urticaria.

BACKGROUND: Cholinergic urticaria does not respond well to treatment with conventional antihistamines and is difficult to study because of its highly variable clinical expression which depends on the presence of eliciting factors. OBJECTIVE: We have therefore designed a double-blind, crossover, placebo-controlled trial, with a 3-week treatment period using either 20 mg/day of cetirizine or placebo. METHODS AND RESULTS: Presence of eliciting factors and symptoms were scored daily on a diary card by the patient, with a scale from 0 to 3 for erythema, wheals and pruritus. Statistical analysis was done on 11 evaluable patients during the last 2 weeks of each treatment period (to allow for 1 week of washout) and only for days when eliciting factors were present. Compared to placebo, cetirizine caused a statistically significant reduction of wheals (p = 0.015), erythema (p = 0.033), pruritus (p = 0.006) and all symptoms (p = 0.013). No adverse events were observed. CONCLUSION: These data show a high efficacy of cetirizine at twice its normally recommended dose which may be related to the specific antiallergic effects of this newer-generation antihistamine.

Adolescent↗
PubMed1996

Quantitative detection of soluble adhesion molecules in sera of melanoma patients correlates with clinical stage.

BACKGROUND: Adhesion is crucial in the metastatic process of malignant tumours. Recently, the expression of certain selectins on intratumoral vessels has been shown to be associated with the clinical outcome of melanoma patients. OBJECTIVES AND METHODS: For the first time, this study examines the serum concentrations of circulating soluble vascular cellular adhesion molecule 1 (CD 106), endothelial leucocyte adhesion molecule (CD62E), sP-selectin (CD62P) and sCD44v5 in comparison to soluble intercellular adhesion molecule 1 (sICAM-1, CD54) in a series of 34 melanoma patients at different clinical stages and 11 normal donors using ELISA: RESULTS: sICAM-1 and sP-selectin levels were statistically elevated in all subgroups of melanoma patients compared to controls (p < 0.01). Circulating ICAM-1 as well as sP-selectin might be valuable additional serological tumour markers which correspond to tumour load and correlate with progression of malignant melanoma. CONCLUSION: Measurement of sICAM-1 and sP-selectin serum levels might therefore provide a sensitive tool for monitoring the clinical course of melanoma.

Adult↗
PubMed1996

Acute urticaria: clinical aspects and therapeutic responsiveness.

Although acute urticaria is common, its eliciting factors, clinical course and therapeutic responsiveness have not been intensively investigated. We have therefore prospectively studied all patients with acute urticaria attending the department of dermatology (n = 72) and a rural dermatology office (n = 37) during the course of 1 year. After a standardized history and physical examination, patients were randomized into treatment with either loratadine (10 mg/day for 3 days) or prednisolene (50 mg/day for 3 days). All patients were followed up until complete remission. Most patients suffered from moderate (42%) to severe (40%) disease. Possible eliciting factors were identified in less than 50% of the cases. Associated upper respiratory tract infections were found most commonly (39.5%), followed by possibly eliciting drugs, mostly analgesics (9.2%) and suspected food intolerance (0.9%). The course of the disease was self-limited in all cases, the longest episode lasting for 3 weeks. Both treatment regimens were effective in controlling whealing, but in corticosteroid-treated patients, symptoms ceased earlier, with complete remission occurring within 3 days of treatment in 93.8%, compared to 65.9% of patients treated with loratadine (p < 0.001). Acute urticaria is thus frequently idiopathic and only rarely associated with IgE-mediated events. It is, however, largely self-limited, with prompt response to symptomatic treatment.

Acute Disease↗
PubMed1995

Gangliosides enhance IgE receptor-dependent histamine and LTC4 release from human mast cells.

Releasability of mast cells and basophils to an IgE-dependent stimulus is regulated by extra- and intracellular factors which are only partly understood. As gangliosides are known to modulate receptor-dependent processes in various cell types, we have evaluated the effect of these molecules on mast cell mediator release. Human skin mast cells and the human mast cell line HMC1 were pretreated with the gangliosides GM2, GM3 and GD1a as well as with asialo-GM3, heparin and buffer alone (controls). After washing, the cells were stimulated with anti-IgE, calcium ionophore A 23187, N-FMLP or substance P. All gangliosides but not asialo-GM3 and heparin augmented anti-IgE-induced mediator release in a dose-dependent fashion, whereas the release to A 23187, N-FMLP and substance P remained unaffected. Only sequential but not simultaneous addition of ganglioside and anti-IgE showed an enhancement in mediator release compared to controls. Mediator release in both ganglioside-pretreated cells and controls was calcium-dependent and could be inhibited by pretreatment of cells with staurosporine or dibutyryl cAMP, indicating an unchanged signal transduction. Gangliosides appear to specifically optimize IgE-receptor-ligand interaction and alterations in cellular gangliosides could thus induce enhanced releasability as observed in atopics.

Cell Line↗
PubMed1995

Serum manganese superoxide dismutase is a new tumour marker for malignant melanoma.

Malignant melanoma in its disseminated stage is incurable. The most widely accepted criteria for the prognostic evaluation of melanoma are histopathological and clinical parameters, and the identification of additional simple, serological tumour markers is thus of paramount importance. Manganese-containing superoxide dismutase (MnSOD) belongs to a family of metalloproteins that catalyse the metabolization of oxygen radicals in order to protect these cells from radical damage. In patients with epithelial ovarian carcinomas, serum MnSOD levels have been shown to be elevated in accordance with the progression of their clinical disease. Recently, an overexpression of MnSOD was shown to suppress the malignant phenotype of human malignant melanoma cells. Therefore, we determined serum MnSOD concentrations in 33 patients with malignant melanoma at different clinical stages. Whereas MnSOD serum levels in normal subjects (n = 11) and in dermatological patients with type I allergies (n = 10) or chronic non-allergic urticaria (n = 7) were below 200 ng/ml, the MnSOD serum concentrations in melanoma patients were statistically elevated in all clinical stages compared with normal (p < 0.005). These data suggest that elevated MnSOD serum concentrations correspond to tumour load and correlate with progression of malignant melanoma. Measurement of MnSOD serum levels might therefore provide a sensitive tool for monitoring the clinical course of melanoma.

Adult↗
PubMed1995

Mast cells.

Explore the source record for details and available documents.

Animals↗
PubMed1995

Mast cells in the cytokine network: the what, where from and what for.

The basic understanding of mast cell ontogeny and function has been fundamentally changed in recent years with observations that the cells produce and respond to a broad range of cytokines. These rapidly accruing data and their potential significance were discussed at the recent symposium "Mast Cells in the Cytokine Network", and the overview lectures of most speakers are summarized in this special journal issue. In the present introductory manuscript, the organizers of the meeting discuss data fundamental to an understanding of the topic and highlight aspects of special interest. They consider mast cells to be defined most reliably by their unique ultrastructure since the cells are highly heterogeneous in dependence of the species studied, their tissue location, their stage of development and probably also in relation to cytokines. Most other characteristics of mast cells are shared with diverse other cell types. Murine mast cell development is induced by several cytokines. These factors are mostly ineffective in human cells except for stem cell factor which causes mast cell development from CD34+/c-kit+ progenitors. There is however recent evidence that fibroblasts and keratinocytes produce additional growth factors for human mast cells. Regarding cytokine secretion, most molecules known so far are produced by both murine and human mast cells. The cells furthermore bear receptors for several cytokines, enabling them to respond in an autocrine and paracrine fashion. Mast cells may thus function within a complex cytokine network, affecting physiological as well as immunological and inflammatory processes.

Animals↗
PubMed1995

Effect of CC chemokines on mediator release from human skin mast cells and basophils.

Chemokines are considered important mediators of various inflammatory processes. In human basophils, different CC chemokines are known to stimulate release of histamine and generation of leukotriene (LT)C4. In the present study, we have evaluated the effect of RANTES (regulated upon activation, normal T cell expressed and secreted), monocyte chemotactic protein (MCP)-1, MCP-2, MCP-3, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta on mast cell activation. Whereas all these CC chemokines caused dose-dependent release of histamine from basophils in mixed human leukocyte suspensions, none of them was able to induce release of histamine as well as tryptase or prostaglandin (PG)D2 from human skin mast cells, nor did priming with these substances enhance IgE-mediated mediator release. In addition, all chemokines failed to promote changes in the cytosolic free calcium level in the human mast cell line HMC-1. These results add further evidence for the differences between human mast cells and basophils regarding cytokine-dependent activation.

Basophils↗
PubMed1995

Efficacy of cetirizine in cholinergic urticaria.

In order to examine the efficacy of cetirizine in cholinergic urticaria, we studied 24 patients in a double-blind crossover design during 3-week treatment periods, with either 10 or 20 mg/d cetirizine or placebo. The placebo period was always placed in between the two verum treatments to allow for a washout of the drug. Evaluation of the patients' daily symptom scores based on itching, erythema and whealing showed a highly significant improvement (p < 0.01). The percentage of days with mild or no symptoms was also increased significantly with the drug (p < 0.05). Except for whealing (p < 0.05), no significant differences between the two dosages of cetirizine could be determined. Since antihistamines have previously been shown to be frequently unsatisfactory in the treatment of cholinergic urticaria, the present data are encouraging regarding the control of symptoms in this condition.

Adult↗