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Biomedical subjects

Margitta Worm

Publications and source records attributed to Margitta Worm.

At least 19 recordsLinked to original sources

A cold-response index for the assessment of Raynaud's phenomenon.

BACKGROUND: Quantification of Raynaud's phenomenon (RP) is a prerequisite in the evaluation of novel therapeutic strategies. Fingertip rewarming in response to local cold provocation has been used in many studies but not been systematically validated. We have previously described the time elapsed before 63% of pre-cooling temperature is reached as a RP activity index. OBJECTIVE: A comprehensive evaluation of fingertip rewarming in primary and scleroderma-associated RP. METHODS: We defined a cold-response index (CRI) as the log transformation of the 63% rewarming time upon cold challenge. RESULTS: The CRI shows high intra-individual reproducibility. The mean CRI values were (mean+/-S.D.): 2.4+/-0.3 in controls (n=53) versus 2.7+/-0.3 in RP (n=50, p<0.0001 versus controls), and 2.7+/-0.3 in scleroderma patients (n=46, p<0.0001). In addition, baseline fingertip temperature was also found to be significantly reduced both in primary as well as scleroderma-associated RP. Kinetic analysis of rewarming temperature curves demonstrates that the CRI is independent of individual rewarming patterns. Finally, the CRI decreases significantly upon a single low-level systemic hyperthermia treatment in scleroderma patients (2.68+/-0.28 before versus 2.45+/-0.33 after, p=0.0003), while the extent of cooling remained unchanged, thus demonstrating sensitivity to change. CONCLUSION: Our results provide a solid basis for using the cold-response assay as an endpoint in addition to clinical activity scores in RP treatment trials.

Adult↗

Classical conditioning and expectancy in placebo hypoalgesia: a randomized controlled study in patients with atopic dermatitis and persons with healthy skin.

The effectiveness of placebos is unchallenged. However, it is still not clear on which mechanisms the placebo effect is based. Besides expectancy theories, classical conditioning is discussed as a major explanatory model. In an experimental conditioning design we tested 96 participants, 48 with atopic dermatitis (24 male, 24 female) and 48 with healthy skin (24 male and 24 female). All of them received a neutral ointment with a different briefing ("pain-reducing ointment" versus "neutral ointment"). Electrical pain stimuli were subsequently applied, which selectively induce a painful sensation. In the case of the learning condition (classical conditioning) and unbeknown to the participants, the intensity of the pain stimulus was reduced by 50% after the ointment had been applied. The study addressed the question whether the pain experienced by the patients with atopic dermatitis could be reduced through a placebo effect and whether the placebo effect was achieved through expectancy or through a process of classical conditioning or both. The results indicate that a placebo effect is achieved via expectancy and classical conditioning. However, conditioning processes seem to be necessary for a longer lasting effect. The extent of this effect seemed to be greater in atopics than in healthy controls. Expectancy, achieved through verbal instruction, might also be seen as a conditioned stimulus that reactivates earlier stimulus associations.

Adolescent↗

Filaggrin loss-of-function mutations predispose to phenotypes involved in the atopic march.

BACKGROUND: Childhood eczema often precedes the development of asthma and allergic rhinitis in the so-called atopic march. Recently, 2 loss-of-function mutations in the gene encoding the epidermal barrier protein filaggrin were reported to be predisposing factors for eczema and concomitant asthma, suggesting a possible role in disease transition. OBJECTIVE: We aimed to assess the importance of filaggrin loss-of-function mutations in the susceptibility to eczema and associated clinical phenotypes. METHODS: The filaggrin mutations were genotyped and tested for association with allergic disorders in 2 large European populations including 1092 children with eczema. RESULTS: Highly significant association of the filaggrin null mutations with eczema and concomitant asthma was replicated. Moreover, we found that these mutations predispose to asthma, allergic rhinitis, and allergic sensitization only in the presence of eczema. We show that the presence of 2 filaggrin null alleles is an independent risk factor for asthma in children with eczema, and that the 2 investigated mutations account for about 11% of eczema cases in the German population. CONCLUSION: These results lend strong support to the role of filaggrin in the pathogenesis of eczema and in the subsequent progression along the atopic march. The fact that previous expression of eczema is a prerequisite for the manifestation of allergic airways disease and specific sensitization highlights the importance of the epidermal barrier in the pathogenesis of these disorders. CLINICAL IMPLICATIONS: Our results suggest that the maintenance and repair of the epidermal barrier in infants with eczema may prevent the subsequent development of allergic airways disease.

Asthma↗

Frequency of atopic dermatitis and relevance of food allergy in adults in Germany.

Many factors may aggravate atopic dermatitis. The aim of this study was to determine the frequency of atopic dermatitis in an unselected population sample and to evaluate the role of food allergy. Patients with atopic dermatitis were recruited from the population in Berlin, Germany, using a postal questionnaire. Skin prick tests for allergens were performed, followed by food challenges. A total of 1739 questionnaires was returned. In all, 23.5% of patients stated that they had atopic dermatitis, and 146 persons (8.4%) fulfilled our atopic dermatitis criteria after a detailed telephone interview. Of these, 111 were examined, and 28 (1.6%) were identified as currently suffering from atopic dermatitis. Twenty-seven patients were further evaluated: 9/27 were found to be skin prick test negative, 19/27 were skin prick test positive either to pollen and/or food allergens. Nine of 27 were challenged with the suspected food allergen: 1/9 showed a worsening of the eczema, 3/9 had oral symptoms, and 5/9 were negative. In conclusion, only 20% of adults with a positive history of atopic dermatitis show active eczema lesions at a given time point. The data indicate that most individuals with atopic dermatitis were sensitized against pollen allergens and according to that, pollen-associated food allergens. A non-selected AD patient cohort does not frequently suffer from clinically relevant pollen-associated food allergy.

Adolescent↗

Direct access to CD4+ T cells specific for defined antigens according to CD154 expression.

The direct assessment of T helper (T(H))-cell responses specific for antigens is essential to evaluate pathogenic and protective immunity. Presently, analysis and isolation of antigen-specific T(H) cells is restricted to cells that produce cytokines, or can be performed only with a rare selection of specific peptide major histocompatibility complex class II (MHC II) multimers. Here we report a new method that enables the assessment and isolation of T(H) cells specific for a defined antigen according to CD154 expression induced after stimulation in vitro. We show that antigen-induced CD154 expression is highly sensitive and specific for human and mouse antigen-specific T(H) cells. Moreover, the isolation of antigen-specific CD154(+) T(H) cells necessitates only surface staining with antibodies, thereby enabling the fast generation of antigen-specific T(H) cell lines. Our approach allows assessment of T(H) cells with a defined specificity for the combined quantitative and qualitative analysis of T(H)-cell immunity as well as for the isolation of specific T(H) cells for targeted cellular immunotherapies.

Animals↗

Introducing genetic testing for adult-type hypolactasia.

BACKGROUND AND AIMS: To evaluate genotyping for two DNA variants (c.1993+327C>T and c.1438+117G>A), recently found to be associated with adult-type hypolactasia, in the diagnosis of lactose intolerance. METHODS: In total, 166 consecutive patients with gastrointestinal symptoms mimicking hypolactasia admitted to the clinic between March 2002 and December 2002 were included. Genotyping for the two DNA variants (c.1993+327C>T and c.1438+117G>A) and standard H2 breath test was performed. RESULTS: Among 116 patients with positive H2 breath test, the c.1993+327C variant was detectable in 106 (91.4%) patients. Among 50 patients with negative H2 breath test, the c.1993+327C variant was seen in 2 patients. Sensitivity, specificity, positive and negative predictive values for the c.1993+327C variant were 91.4, 96.0, 98.1 and 82.8%, respectively. Genotyping for the c.1438+117G variant did not bring any additional information. Among 4 of the 10 patients with positive H2 breath test but negative for the c.1993+327C and the c.1438+117G variant,further evaluation revealed other diseases known to cause secondary hypolactasia such as celiac disease and short bowel syndrome. CONCLUSION: In symptomatic patients, genotyping for the DNA variant c.1993+327C is a reliable test for adult-type hypolactasia with high sensitivity and specificity and thus provides a new tool in the diagnostic workup of hypolactasia.

Blood Glucose↗

[Efficacy of tracrolimus 0.1% ointment in prurigo].

BACKGROUND: Potent topical corticosteroids are used the intense pruritus in prurigo diseases. Their long-term application leads to local side effects such as atrophy and telangiectasia. PATIENTS AND METHODS: We treated 6 women (average age 64 years) with chronic prurigo with tacrolimus 0.1 % ointment (Protopic) to evaluate its efficacy in this clinical setting. Tacrolimus 0.1% ointment was applied twice a day for 4 weeks. RESULTS: After one week, both clinical improvement and reduced pruritus were observed in all patients. CONCLUSION: Tacrolimus 0.1% ointment represents a therapeutic option for the treatment of prurigo.

Aged↗

Immunoglobulin E-reactivity of wheat-allergic subjects (baker's asthma, food allergy, wheat-dependent, exercise-induced anaphylaxis) to wheat protein fractions with different solubility and digestibility.

Baker's asthma, food allergy to wheat, and wheat-dependent, exercise-induced anaphylaxis (WDEIA) are different clinical forms of wheat allergy. We investigated the correlation of solubility and digestion stability of wheat allergens with the IgE-reactivity patterns of different patient groups. Three wheat protein fractions were extracted according to their solubility: salt-soluble albumins and globulins, ethanol-soluble gliadins, and glutenins soluble only after treatment with detergents and reducing reagents. Sera from subjects with history of each variant of wheat allergy were characterized by CAP FEIA and immunoblotting. There was a high degree of heterogeneity of recognized allergens between the different subject groups as well as within these groups. However, subjects with WDEIA showed similar immunoglobulin E (IgE)-reactivity patterns to gliadins and especially to a 65 kDa protein. Subjects with baker's asthma as well as the food-allergic subjects had the most intense IgE-reactivity to the albumin/globulin fraction. The latter group additionally showed IgE-reactivity to the other fractions. Divergent results of immunoblotting and CAP-FEIA demonstrated that the detection of wheat-specific IgE highly depends on the applied method, thus the diagnostic tool must be carefully chosen. Most wheat allergens were rapidly digested as analyzed by determination of IgE-reactivity on immunoblots to wheat extracts after simulation of gastric and duodenal digestion. However, ethanol-soluble gliadins were stable to gastric enzymes and exhibit low solubility in gastric and duodenal fluids. Therefore, they are likely to be important in food allergy to wheat.

Albumins↗

Modulation of cytokine production by low and high retinoid diets in ovalbumin-sensitized mice.

Retinoids modulate many physiological processes such as the differentiation and growth of different cell types, including cells from the immune system. We have previously shown that retinoids modulate IgE production in vitro and in vivo. In the present study we investigated the effects of retinoids in non-sensitized and ovalbumin-sensitized mice that were fed for 11 weeks with three different vitamin A (VA) diets: a) VA-deficiency diet, b) base diet, and c) base diet supplemented with 0.5% all-trans-retinoic acid (ATRA). Phorbol-myristate-acetate (PMA)/ionomycin-stimulated SMC (splenic mononuclear cells) from mice fed with ATRA and the vitamin A-deficient diet group showed increased interleukin-4 (IL-4) responses in non-sensitized mice. After ovalbumin sensitization in the VA-deficient and the ATRA supplementation diet groups, no significant effects on IL-4 production were observed. By contrast, gamma interferon (IFN-gamma production from PMA/ionomycin-stimulated SMC was enhanced in the VA-deficient diet group in ovalbumin-sensitized mice, and also in non-sensitized mice compared to the base and the ATRA-supplemented diet group. The data indicate that VA and retinoid content in a diet influences the cytokine response in non-sensitized and also ovalbumin-sensitized mice. Therefore these molecules may serve as active modulators of cytokine production in vivo that are responsible for the induction and persistence of atopic diseases.

Animals↗

Frequency of contact allergy in German children and adolescents patch tested between 1995 and 2002: results from the Information Network of Departments of Dermatology and the German Contact Dermatitis Research Group.

Allergic contact dermatitis (ACD) affects approximately 7% of the general population. To evaluate the frequency of ACD in children, we analysed patch test results collected by the Information Network of Departments of Dermatology between 1995 and 2002. Data of 285 children (6-12 year) and 2175 adolescent patients (13-18 year) were analysed to determine the frequency of sensitization to the 30 most common contact allergens, adjusting for age and sex. As control group, we defined adult patients (60-66 year, n = 7904). The top allergens in children were thimerosal, gentamicin sulphate, nickel-II-sulphate, ammoniated mercury, cobalt-II-chloride, fragrance mix, bufexamac, Compositae mix, propylene glycol and turpentine. The overall proportion of sensitized patients according to the patch test results was 52.6% in the children group compared to 49.7% in the adolescent group. These findings were similar in the adult group at 52.2%. The detailed analysis regarding sex, occupation, atopy, site of eczema and age showed distinct patterns in each group indicating age-specific exposures. Atopy-related diseases were more common in children compared to adults. On the basis of the data of this study, the relationship between atopy and the risk of development of ACD, at least in children, needs further investigation.

Adolescent↗

Long-term efficacy and safety of pimecrolimus cream 1% in adults with moderate atopic dermatitis.

BACKGROUND: Pimecrolimus cream 1% is a non-steroid, selective inflammatory cytokine inhibitor indicated for atopic dermatitis (AD). OBJECTIVE: To compare the safety and efficacy of pimecrolimus cream 1%-based treatment versus conventional therapy in adults with moderate AD. METHODS: Patients were randomized to receive pimecrolimus cream 1% (n = 62) or vehicle (n = 68) at the first signs/symptoms of AD, for 24 weeks as required. A moderately potent topical corticosteroid (prednicarbate 0.25% cream) was allowed in both groups to treat flares. RESULTS: Corticosteroids were required on fewer days in the pimecrolimus group, compared with the vehicle group (9.7 vs. 37.8%, p < 0.001). Furthermore, 59.7% of pimecrolimus-treated patients experienced no flares during the study period, compared with 22.1% of vehicle-treated patients (p < 0.001). Pimecrolimus cream 1% was well tolerated throughout the study. CONCLUSION: For adults with moderate AD, pimecrolimus cream 1% is well tolerated, reduces the incidence of flares, reduces/eliminates corticosteroid use, improves long-term disease control and enhances the patients' quality of life.

Administration, Cutaneous↗

[Successful treatment of Stewart-Treves syndrome with liposomal doxorubicin].

The Stewart-Treves syndrome (STS) is a lymphedema-associated angiosarcoma which usually develops in female patients after mastectomy and axillary lymph node dissection. A 55-year old woman developed STS in her lymphedematous left arm seven years after breast-preserving surgery with axillary lymph node dissection and radiotherapy. Various therapies which have been employed are radiotherapy and isolated limb perfusion with cytostatic agents. Since our patient had a huge lesion with additional chest wall involvement, neither approach represented a good option. Radiological staging showed no evidence of further lesions or metastases. We started infusion therapy with liposomal doxorubicin (20 mg/m2 body surface) fort six cycles at regular intervals of 14 days. The patient tolerated the therapy well. Palmar-plantar erythrodysesthesia, a well-known side effect of doxorubicin, did develop. Because the disease was stable, the therapy interval was increased to six weeks after the 6th cycle. The patient has shown no recurrence for eight months. STS is a very rare variant of an angiosarcoma with poor prognosis. The case report shows that liposomal doxorubicin provides an effective therapeutic option.

Antibiotics, Antineoplastic↗