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Biomedical subjects

S Wöhrl

Publications and source records attributed to S Wöhrl.

16 recordsLinked to original sources

The performance of a component-based allergen-microarray in clinical practice.

BACKGROUND: Currently, the diagnosis of IgE-mediated allergy is based on allergen-specific history and diagnostic procedures using natural allergen extracts for in vivo and in vitro tests. OBJECTIVE: The aim of the study was to comparatively analyse a new component-based allergen-microarray and the 'quasi-standard' ImmunoCAP for their clinical relevance in patients with allergic rhinoconjunctivitis to five aeroallergens [house dust mite (HDM), cat dander, birch, grass and mugwort pollen] in a prospective, double-centre study. METHODS: We enrolled 120 subjects at the two study centres. Allergic patients were defined as having an allergen-specific history plus a concomitant positive skin-prick test (SPT) to natural allergen extracts and specific serum IgE was measured by both methods. Each allergen was analysed separately. RESULTS: The microarray performed equally well in receiver-operating characteristic curve (ROC) analyses when compared with the CAP in cat (23 allergic vs 97 non-allergic, ROC area under the curve microarray 0.950 vs CAP 0.894, P = 0.211), birch (31/89, 0.908 vs 0.878, P = 0.483) and grass pollen (47/73, 0.923 vs 0.915, P = 0.770). It was slightly less sensitive in HDM-allergic subjects (26 allergic vs 94 non-allergic, ROC area microarray 0.808 vs CAP 0.911, P = 0.053) and displayed a reduced sensitivity in the mugwort pollen-allergic patients (17/103, 0.723 vs 0.879, P = 0.032). CONCLUSIONS: Component-based testing and the whole-allergen CAP are equally relevant in the diagnosis of grass-, birch- and cat-allergic patients. Although slightly less sensitive, the microarray is sufficient for the diagnosis of HDM-allergic patients, but needs alternative and/or additional components for detecting mugwort allergy.

Adult↗

Patients with drug reactions -- is it worth testing?

BACKGROUND: Unevaluated drug reactions that lead to the prescription of expensive alternative medication is the reason why the European Academy of Allergy and Clinical Immunology guidelines recommend verification. We evaluated whether a structured test procedure in patients with drug reactions is worth the potential risk. METHODS: We retrospectively analysed the charts of a cohort of 291 (220 females/71 males) consecutive patients from January 2003 to June 2004, who presented at the department's allergy outpatient clinic with histories of drug reactions. Twenty-three patients reported more than one independent episode resulting in 325 cases. All patients underwent the following procedure: (1) detailed history; (2) skin test and/or beta-lactam-specific IgE and; (3) if inconclusive, each patient was offered provocation testing -- if needed with alternative medication. RESULTS: We evaluated reactions to 130 antibiotics, 90 to nonsteroidal anti-inflammatory drugs, 36 to local anaesthetics and 69 to other drugs. An association between drug intake and reaction was confirmed in 100 and excluded in 157 cases. Fourteen of 104 drug provocation tests (DPT), among these four reactions to placebo, yielded positive results but were managed without difficulty. In 68 cases, the procedure remained inconclusive. Additionally, we recommended 197 safe alternative regimens to 85 patients. Overall, our test procedure resulted in clear-cut recommendations to 82.1% (239/291) of the patients. CONCLUSIONS: A standardized work-up including DPTs in patients with drug reactions leads to clear-cut advice concerning future tolerability or avoidance of certain drugs including recommendations for alternative medication in the vast majority of patients at the cost of only a low risk of mild side effects.

Adult↗

Standard skin prick testing and sensitization to inhalant allergens across Europe--a survey from the GALEN network.

Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA(2)LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15-20 min exposure with positive results defined as a wheal >3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA(2)LEN Pan-European core SPT panel.

Administration, Inhalation↗

L-type Ca2+ current downregulation in chronic human atrial fibrillation is associated with increased activity of protein phosphatases.

BACKGROUND: Although downregulation of L-type Ca2+ current (I(Ca,L)) in chronic atrial fibrillation (AF) is an important determinant of electrical remodeling, the molecular mechanisms are not fully understood. Here, we tested whether reduced I(Ca,L) in AF is associated with alterations in phosphorylation-dependent channel regulation. METHODS AND RESULTS: We used whole-cell voltage-clamp technique and biochemical assays to study regulation and expression of I(Ca,L) in myocytes and atrial tissue from 148 patients with sinus rhythm (SR) and chronic AF. Basal I(Ca,L) at +10 mV was smaller in AF than in SR (-3.8+/-0.3 pA/pF, n=138/37 [myocytes/patients] and -7.6+/-0.4 pA/pF, n=276/86, respectively; P<0.001), though protein levels of the pore-forming alpha1c and regulatory beta2a channel subunits were not different. In both groups, norepinephrine (0.01 to 10 micromol/L) increased I(Ca,L) with a similar maximum effect and comparable potency. Selective blockers of kinases revealed that basal I(Ca,L) was enhanced by Ca2+/calmodulin-dependent protein kinase II in SR but not in AF. Norepinephrine-activated I(Ca,L) was larger with protein kinase C block in SR only, suggesting decreased channel phosphorylation in AF. The type 1 and type 2A phosphatase inhibitor okadaic acid increased basal I(Ca,L) more effectively in AF than in SR, which was compatible with increased type 2A phosphatase but not type 1 phosphatase protein expression and higher phosphatase activity in AF. CONCLUSIONS: In AF, increased protein phosphatase activity contributes to impaired basal I(Ca,L). We propose that protein phosphatases may be potential therapeutic targets for AF treatment.

Aged↗

Specific sensitization to the common housefly (Musca domestica) not related to insect panallergy.

BACKGROUND: Allergy to houseflies is rare. We report a case of respiratory allergy from occupational exposure to houseflies in a farmer. CASE REPORT: A 30 year-old female farmer with a long-standing history of grass pollen allergy observed for 2 years rhino-conjunctivitis and mild asthma when entering livestock stables and barns. Allergy retesting revealed sensitization to various pollens but not to animal danders. Houseflies (Musca domestica) occurring on the farm in great quantity were suspected by the farmer herself as the causative agent. RESULTS: Skin prick testing with housefly was positive in the patient and negative in four controls. Experimental radioallergosorbant test was class 3 positive. Sensitization to house dust mite, storage mites and cockroach was not detectable. Western blots with housefly extracts revealed immunoglobulin E (IgE)-binding to bands of 70, 50, and approximately 16 kDa. Tropomyosin in the housefly extract (35 kDa) was recognized by a tropomyosin reference serum but not by the patient. In enzyme-linked immunosorbent assay (ELISA) inhibition assays using housefly as the solid phase, IgE-binding of the patient was inhibited by 75% by M. domestica and by 44% by the closely related lesser housefly (Fannia canicularis), but not by extracts from blowfly (Lucilia spp.), fruit fly (Drosophila spp.), horsefly (Haematopota pluvialis) and mosquito (Culex pipiens). The IgE-binding of the tropomyosin control serum was inhibited by 60-80% by all species. CONCLUSIONS: In accordance with previous reports, this case demonstrates that respiratory sensitization to insects may be highly specific. According to ELISA inhibition, cross-sensitization in the present case was restricted to species of the family of true flies (Muscidae).

Adult↗

Cross-reactivity between Ficus benjamina latex and fig fruit in patients with clinical fig allergy.

BACKGROUND: Anaphylactic reactions to fig fruits (Ficus carica) have been reported from subjects sensitized to Ficus benjamina (FB) latex allergens. Figs may also be involved in the latex-fruit syndrome. OBJECTIVE: To study the immunologic relationship between fig fruit, Ficus benjamina, natural rubber latex (Hevea brasiliensis), and other tropical fruits. METHODS: RAST inhibition and Western blotting with FB and fruit extracts was performed in five patients with oral allergy syndrome (OAS) or anaphylaxis after the ingestion of figs and one patient with symptoms from exposure to FB trees. Co-sensitization to rubber latex and tropical fruits (kiwi, banana, avocado, papaya, pineapple, mulberry) was studied by skin testing. RESULTS: RAST to FB was inhibited >95% by FB extracts and 16-65% (mean 49%) by extracts from fresh fig. RAST to fig fruit was inhibited >95% by FB and fresh fig, 63-97% (mean 86%) by dried fig, and 0-84% (mean 35.5%) by kiwi fruit. FB and fig extracts lost most of their allergenicity when denatured by heat (95 degrees C) or reduced by dithiothreitol. Western blotting after non-reducing gel electrophoresis revealed IgE binding to proteins of 22 and 28-34 kDa in FB latex; however, no corresponding allergens could be detected in fig extracts. Positive skin tests were obtained most often with kiwi fruit, papaya, and avocado. Sensitization to rubber latex could not be demonstrated in any of the patients. RAST to papain was positive in three of five patients. CONCLUSIONS: Allergic reactions to fresh or dried figs can present as a consequence of primary sensitization to airborne FB allergens independent of sensitization to rubber latex allergens. Kiwi fruit, papaya, and avocado as well as pineapple and banana may be other fruits associated with sensitization to Ficus allergens.

Allergens↗

A cream containing the chelator DTPA (diethylenetriaminepenta-acetic acid) can prevent contact allergic reactions to metals.

Chelating agents in protective barrier creams have often been used in the prevention of allergic contact dermatitis to nickel. In a pilot study, we demonstrated the preventive effect of 10% diethylenetriaminepentaacetic acid (DTPA) in an oil-in-water emulsion in nickel-sensitized patients. Now we reproduced these results in a randomized, double-blind study. Additionally, we investigated the efficacy of the barrier cream in other clinically relevant metal allergies. Individuals sensitized to various metals had a significant decrease in positive patch test reactions after pre-treatment with the DTPA-cream: 2.5% nickel sulfate (24/28 positive without pre-treatment versus 1/28 with pre-treatment; p<0.0001), 5% nickel sulfate (30/32 versus 15/32; p=0.0003), 1% cobalt chloride (19/20 versus 6/20; p=0.001) and 5% copper sulfate (13/14 versus 5/14; p=0.02). However, the cream had no protective effect with 1% palladium chloride (17/23 versus 16/23) and with 0.5% potassium dichromate (9/13 versus 7/13). We conclude that the DTPA-cream clearly abrogates positive patch test reactions in nickel-, cobalt- and copper-sensitized subjects and that it may therefore be helpful in the management of allergic contact dermatitis.

Chelating Agents↗

The significance of fragrance mix, balsam of Peru, colophony and propolis as screening tools in the detection of fragrance allergy.

BACKGROUND: Patch testing to fragrances is an important step in the diagnosis of fragrance allergy. OBJECTIVES: To determine the usefulness of adding propolis to the European standard series to test for fragrance allergy. PATIENTS AND METHODS: A total of 2660 consecutive patients were patch tested with a standard patch test series; 747 suspected of fragrance allergy were tested further with a special fragrance series. RESULTS: The positive results to the standard series in 2660 patients were: fragrance mix 243 (9.1%), Myroxylon Pereirae [balsam of Peru] 144 (5.4%), colophony 32 (1.2%); these fragrance mixtures are used as screening substances for fragrance allergy in the European standard series. Propolis, also known as bee's glue, was also an important allergen in this locally revised standard series (n = 35, 1.3%). Positive reactions to the aforementioned allergens were associated significantly among each other (P < 0.01, chi2-test) and did not differ between the sexes. The primary locations of dermatitis in patients with a positive test to one or more fragrance allergens (n = 162) among those suspected of fragrance allergy (n = 747) were: face 46.9%, hands 23.5%, neck 17.9%, axillae 12.3%; 92 of the 747 patients suspected of fragrance allergy had positive skin tests to the special fragrance series comprising the eight constituents of the fragrance mix (most frequent: isoeugenol 5.4%, oakmoss absolute 5.0%, eugenol 2.5%) and 14 other fragrance allergens (most frequent: clove oil 1.6%, lemon grass oil 0.8%, cedar wood oil 0.7%). The additional value of propolis as another screening substance for fragrance allergy in these patients was low. The likelihood of a reaction to one or more of the extra fragrance allergens increased with the number of reactions to fragrance screening allergens in the standard series. CONCLUSIONS: The number of positive reactions to fragrance screening allergens in a standard patch test series may be used as a rule of thumb for predicting a positive outcome of a more detailed testing to fragrances. Propolis is an important allergen in its own right but its value as a screening substance for fragrance allergy is limited.

Adult↗

Hypopigmentation after non-permanent henna tattoo.

A young girl presented with a hypopigmentation in the shape of the sun. During a holiday in Egypt 3 months before a non-permanent henna tattoo had been applied on her right upper arm. Three to 4 days later there was a severe cutaneous reaction followed by massive swelling of the arm. The lesion took 6 weeks to subside. Patch testing revealed positive reactions to para-phenylenediamine (PPD) but not to henna or any other standard allergen. Especially in Arabic countries PPD is a common additive in natural henna preparations to enhance the weak colouring properties of the natural henna dye. We conclude that henna preparations may contain 'hidden' allergens, such as PPD, which can provoke severe cutaneous reaction without any cosensitization to the henna dye itself.

Child↗

Antibody binding to venom carbohydrates is a frequent cause for double positivity to honeybee and yellow jacket venom in patients with stinging-insect allergy.

BACKGROUND: Up to 50% of patients with stinging-insect allergy have double-positive RAST results to honeybee and yellow jacket (YJ) venom. True double sensitization and crossreactivity through venom hyaluronidases are considered main reasons for this multiple reactivity. OBJECTIVE: We investigated the role of antibodies against cross-reactive carbohydrate determinants in venom double positivity. METHODS: CAP inhibition experiments were performed with crude oilseed rape (OSR) and timothy grass pollen extracts and a neoglycoprotein construct displaying a MUXF glycan, as present in pineapple-stem bromelain (MUXF-BSA). CAP to OSR was used as a rough measure for carbohydrate-specific IgE in individual sera. RESULTS: CAP results to OSR pollen were positive in 2 of 14 single-positive honeybee venom sera, 2 of 16 single-positive YJ venom sera, and 33 (80.5%) of 41 double-positive sera (P < .00001, chi(2) test). CAP inhibition was performed in 16 selected patients with a CAP class of 3 or higher to both venoms. In 9 of 11 patients with a highly positive CAP result to OSR (CAP score to OSR > CAP score to second venom), pollen extracts, MUXF-BSA, or both were able to completely inhibit IgE binding to one of the venoms, whereas this was not the case in 5 patients with a negative or weakly positive CAP result to OSR (CAP score to OSR < CAP score to second venom). CONCLUSIONS: The data suggest that carbohydrate-specific IgE is a major cause for the double positivity to honeybee and YJ venom seen in patients with Hymenoptera allergy. Because these antibodies may have low clinical relevance, they may severely impede the correct diagnosis of Hymenoptera venom allergy.

Animals↗

Copper allergy revisited.

BACKGROUND: Positive patch tests to copper sulfate are regularly observed, although copper is reported as a rare allergen with a low sensitizing potential. Usually they are claimed to be irritant and unspecific. OBJECTIVE: The aim of this study was to assess the relevance and the diagnostic value of positive reactions to copper. METHODS: A total of 2660 routine patch tests were analyzed for positive reactions to copper and other metal allergens: copper, 3.53%; nickel, 21.02%; palladium, 5.90%; cobalt, 3.31%. RESULTS: Reactions to copper and nickel were highly significantly associated with each other. Twenty-six patients with a positive routine test to copper were retested. The reproducibility was modest (38%), but again significantly associated with nickel sensitization. CONCLUSION: These clinical data support a copper-nickel cross-reactivity concept on T-cell level based on recently published molecular data. We conclude that positive patch tests to copper are mostly specific; however, they are usually of low clinical relevance.

Adolescent↗

Activation of different Stat5 isoforms contributes to cell-type-restricted signaling in response to interferons.

Tyrosine phosphorylation and activation of the transcription factor Stat5 occur in response to stimuli like granulocyte-macrophage colony-stimulating factor, interleukin-3, or erythropoietin that stimulate both proliferation and differentiation of hematopoietic cells. It is unclear whether Stat5 is part of a proliferative response or part of the events leading to cellular differentiation. Here we report that agents promoting differentiation but not proliferation of hematopoietic cells, like phorbol ester or both types of interferons (IFNs), activate Stat5 in promonocytic U937 cells. Both IFN types caused tyrosine phosphorylation and DNA binding of predominantly one Stat5 isoform (Stat5a) despite expression of both Stat5a and Stat5b proteins. Monocytic differentiation of U937 cells led to a strong decrease in IFN-gamma-mediated activation of Stat5 but not of Stat1. Transactivation of Stat5-target genes occurred in response to IFN-gamma, which activates both Stat5 and Stat1, but not in response to granulocyte-macrophage colony-stimulating factor, which activates only Stat5. Tyrosine phosphorylation of Stat5 is not generally part of the IFN response. IFN-gamma did not cause Stat5 activation in HeLa cells, despite the expression of both Stat5 isoforms at similar levels. By contrast, IFN-alpha caused tyrosine phosphorylation and DNA binding of exclusively the b isoform of Stat5, and activated Stat5b formed a DNA binding activity previously found in HeLa cells and designated IFN-alpha activation factor 2. Taken together, our results demonstrate that ligand binding of IFN receptors leads to an isoform-specific activation of Stat5 in a restricted number of cell lineages. Moreover, they suggest that Stat5 might be part of the differentiation response of myeloid cells.

Cell Differentiation↗