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Biomedical subjects

J Brasch

Publications and source records attributed to J Brasch.

At least 37 records · Page 2Linked to original sources

Reproducibility of irritant patch test reactions to sodium lauryl sulfate in a double-blind placebo-controlled randomized study using clinical scoring. Results from a study group of the German Contact Dermatitis Research Group (Deutsche Kontaktallergie-Gruppe, DKG).

Reading of doubtful patch test reactions can be improved by comparing them to defined negative, allergic and irritant controls. For the latter, an irritant patch test is needed that gives sufficiently reproducible results. In our double-blind, placebo-controlled, randomized study, we have analysed the synchronous reproducibility of patch tests with 0%, 0.0625%, 0.125%, 0.25%, 0.5% and 1.0% sodium lauryl sulfate (SLS). Tests and readings were done according to ESCD guidelines. 139 patients (75 women, 64 men) 18 to 77 years old were tested. The % of positive patients as well as the % of reproducible positive reactions increased with rising concentrations of SLS to a maximum of approximately 90% and 85%, respectively, with 1% SLS. Time courses of reactions were also related to the concentration of SLS: with 1% SLS, plateau-type time courses were most common (65%), followed by decrescendo- (23%) and crescendo-type reactions (12%). With 1% SLS, very similar mild to moderate reactions were obtained on days 2 and 3. The reaction threshold and reproducibility of tests were not related to age and sex of patients or to their own assessment of skin irritability. We conclude that 1% SLS is appropriate for an irritant patch test that gives sufficiently reproducible results.

Adolescent↗

[Differentiated contact allergy lists serve in quality improvement].

Through cooperation between the German Contact Dermatitis Research Group (DKG) and the Information Network of Departments of Dermatology (IVDK), results of standardized patch tests performed by the participating centres are centrally recorded in Germany. For this study, data from 24 departments of dermatology (19678 patients) were evaluated retrospectively and separately for 1995 and 1996. With decreasing frequency, nickel, fragrance mix, balsam of peru, and thimerosal yielded positive reactions most often; surprisingly high numbers of positive reactions were also seen with amerchol L-101 and palladium. Differentiated lists of allergens were compiled for 1995, referring to subgroups of patients (defined by gender, age, localization of eczema, geographical region, occupation, sensitization) and particular problems. In men, percentages of positive reactions were markedly lower for nickel, fragrance mix and balsam of peru than in women. Younger patients reacted more often to thimerosal and older ones to topical medical preparations. Medical allergens were also often positive in patients with leg eczema, whereas occupational allergens were found more frequently in patients with hand eczema. A comparison of positive reactions obtained in distinct geographical regions was problematic because of differences between test populations. The spectrum of allergens found in office workers was similar to that of the whole test population. Patients with positive reactions to nickel and fragrance mix had more positive reactions to unrelated allergens than the total test population. Sex- and age-adjusted frequencies of sensitization revealed a decrease in reactions to nickel and an increase in reactions to mercury allergens from 1995 to 1996. The clinical relevance of mercury reactions was often not apparent. Differentiated lists of allergens can be used to improve the quality of diagnostic and prophylactic procedures in allergic contact dermatitis.

Adolescent↗

[Tinea caused by Trichophyton equinum].

We report on the first human infection with Trichophyton equinum in Germany, which was transmitted from an infected pony to a 12-year old girl. Trichophyton equinum was identified by its morphology, dependency on nicotinic acid, hair perforation, and enzyme production. A noteworthy new observation was the development of white pleomorphic tufts on the surface of thalli grown on potatoe-dextrose agar. The girl's tinea was non-inflammatory and responded promptly to topical treatment, whereas the pony's strongly inflammatory lesions persisted for months. In supernatants of cultures supplemented with different nutrients, enzyme patterns were measured for Trichophyton equinum that correspond to other species of dermatophytes more pathogenic for humans. Therefore, a lack of enzymes is apparently not the explanation for the rarity of human infections with Trichophyton equinum. More likely, predisposing factors of the host are necessary in combination with a close contact to infected horses. Treatment of infected humans appears to be no major problem.

Animals↗

Genotype and phenotype of N-acetyltransferase 2 (NAT2) polymorphism in patients with contact allergy.

We investigated whether patients with contact allergy differed from non-contact-allergic, non-atopic controls with regard to genotype and phenotype of the polymorphic enzyme N-acetyltransferase 2 (NAT2). 55 contact-allergic patients recruited from the Information Network of Departments of Dermatology (IVDK) were compared to 85 controls from among local health care personnel. NAT2 activity was calculated from HPLC analysis of the ratio of the caffeine metabolites 5-acetylamino-6-formylamino-3-methyluracil (AFMU) and 1-methylxanthine (1MX) in the urine. NAT2 genotype was determined by polymerase chain reaction (PCR). A statistically significantly increased proportion of rapid acetylators was found in contact-allergic patients. This may have 2 possible implications: acetylation may enhance contact sensitization; or NAT2 status may be a genetic marker for contact sensitizability.

Acetylation↗

[Hormones, fungi and skin].

It is indicated by some epidemiological and clinical observations, that steroidal hormones may belong to those factors that are capable to influence the clinical courses of mycotic infections in man. Several fungal species, including pathogenic ones, are able to produce or metabolize steroidal hormones, or their growth can be affected by such hormones. Since, on the other hand, the steroid-responsive human skin is also capable to synthesize and convert steroidal hormones, the relationship between pathogenic fungi and host may be influenced by hormonal mediators in dermatomycoses.

Dermatomycoses↗

[Dermatophytes do not produce sialidase in vitro].

Sialidase (EC 3.2.1.18) is a pathogenicity factor of many microorganisms, and may also play a role in adhesion of dermatophytes to the epithelia of their hosts by the hydrolytical cleavage of terminal, negatively charged sialic acids of glycoconjugates on the cell surfaces, thus allowing fungal lectins to bind to the subterminal sugars. Therefore, 116 strains of seven species of dermatophytes were investigated for sialidase production. Two highly sensitive, quantitative sialidase assays were applied to cell homogenates and culture supernatants from seven different media of the fungi, but were always negative for sialidase activity. However, sialidase activity was always detected in Ophiostoma stenoceras used as a positive control cultivated in parallel; the enzyme was inducible by sialylated mucins. A sialidase-dependent pathomechanism for dermatophytes appears unlikely based on the results presented.

Animals↗

More positive patch test reactions with larger test chambers? Results from a study group of the German Contact Dermatitis Research Group (DKG).

Test chambers of various sizes are commercially available for patch testing. Therefore, we asked the question whether the size of patch test chambers may affect allergic patch test reactions. A total of 495 patients were double tested synchronously with small and large Finn Chambers containing standard preparations of fragrance mix, wool wax alcohols, Kathon CG and formaldehyde. Double tests in 217 patients who had reacted with at least 1 allergic, questionable, or irritant reaction to 1 of these allergens were statistically evaluated. For each of the 4 allergens, a significantly higher number of stronger reactions was seen with the large chambers as compared to the small ones. It is concluded that large test chambers may be useful for detection of weak sensitizations to particular contact allergens.

Adult↗

Patch test results in schoolchildren. Results from the Information Network of Departments of Dermatology (IVDK) and the German Contact Dermatitis Research Group (DKG)

Our aim was to explore the current spectrum of contact allergens in schoolchildren, as a basis for diagnosis and prevention of allergic contact dermatitis. Results of patch tests in children 6-15 years old, performed in the years 1990-1995 by 22 centres of the German Contact Dermatitis Research Group and filed by the Information Network of Departments of Dermatology, were analysed and evaluated retrospectively, including epidemiologic data. Children with positive tests (62 out of 156 boys and 108 out of 260 girls tested) had a higher frequency of allergic contact dermatitis and a lower frequency of atopic dermatitis than patch test negative ones. 16 distinct allergens elicited positive reactions in > or = 1% of the children tested. Reactions to nickel sulfate occurred in 15.9% of all children tested, but in 25.0% of girls 14/15 years old, and in only 4.5% of boys 6-13 years old. Double-sensitizations with cobalt salts, potassium dichromate and palladium were seen. Mercury compounds were found in 2nd place (thimerosal: all children: 11.3%; 6-13 years old: 14.3%; 14/15 years old: 8.0%), followed by fragrance allergens. We conclude that contact allergy in children is related to their sex and age. Prophylaxis against nickel, mercury, and fragrance allergy needs to be improved. A shortened standard series may be sufficient for testing children.

Adolescent↗

Influence of epidermal permeability barrier disruption and Langerhans' cell density on allergic contact dermatitis.

Previously, we have showed that artificial epidermal permeability barrier disruption leads to an increase in epidermal Langerhans' cell (LC) density within 24 h. We now asked if this is accompanied by an enhancement of allergic contact dermatitis. Barrier disruption was induced by acetone on the upper arms in 6 volunteers with known sensitization to nickel, fragrance mix, or p-phenylenediamine. Twenty-four hours after this treatment the relevant allergen was applied without occlusion or with Finn chambers. Twenty-four hours after application of the allergen, clinical grading and transepidermal water loss (TEWL) measurements were performed and biopsies were taken. Immunohistochemical stainings for LCs (anti-CD1a, Leu6) and for epidermal proliferation (Ki-S3) were performed. Open applications of the allergens after acetone pretreatment resulted in strong allergic test reactions. TEWL, which showed a 70% recovery 24 h after acetone treatment, was increased again 4-fold by the allergic test reactions. LC density, which was increased by 80% 24 h after acetone-induced barrier disruption, was further enhanced 2.4-fold in total. Epidermal proliferation showed a 6-fold increase after open application of the allergens. Under patch test conditions after acetone pretreatment very strong bullous reactions were observed. We conclude that the increase in epidermal LC density induced by epidermal permeability barrier disruption is accompanied by an enhanced response in allergic contact dermatitis.

Acetone↗

[Oral exposure testing in non-aspirin-induced analgesic intolerance].

Although intolerance reaction to analgesics are not uncommon, there is still a lack of standardized procedures to diagnose the problem. We retrospectively analyzed results of scratch tests as well as oral challenges with analgesics in order to evaluate risk and diagnostic relevance of these procedures. In 1987-1992 a total of 650 patients with supposed intolerance to drugs were tested by oral challenge. Among them were 98 patients with a positive history of intolerance to non-aspirin analgesics. In 56 patients the intolerance could be verified by oral challenge. In order of decreasing frequency, the most likely agents were propyphenazone, diclofenac, metamizole, ibuprofen, carbamazepine, indomethacin, phenazone (antipyrine), and paracetamol (acteaminophen). Oral provocation showed clear dose-response relationships. For propyphenazone, the half-effective provocation dose was the same for all symptoms (cutaneous, nasal, bronchial, anaphylactoid). Scratch testing was not of diagnostic significance. Standardized test protocols starting with low dose oral challenges are suitable and helpful in minimizing the risk of severe side effects.

Administration, Oral↗

Dermatophytes contain a novel lipid-like leukocyte activator.

In the early phase of dermatophytosis, neutrophils are regularly detected microscopically in the infected skin. Although neutrophil recruitment may at least in part occur indirectly by complement activation, we asked whether dermatophytes might release chemoattractants for neutrophils. We cultivated various strains of different dermatophytes and tested fungal extracts for the presence of neutrophil chemotactic activity. As a result, we detected neutrophil chemotactic activity only in diethylether extracts, but not in aqueous extracts. We purified this lipid-like leukocyte activator (LILA) to apparent homogeneity by reversed-phase high performance liquid chromatography and found that purified LILA does not show ultraviolet absorption at wavelengths > 210 nm. Biologic studies revealed that LILA is as effective as formyl-methionyl-leucyl-phenylalanine in eliciting neutrophil chemotaxis, degranulation, and activation of the respiratory burst. Desensitization experiments in chemotaxis and degranulation with leukotriene B4, platelet-activating factor, or 5-oxo-eicosanoids revealed that LILA does not cross-desensitize with any of these other lipid-like attractants and thus possibly acts via a distinct as yet postulated neutrophil receptor. It is hypothesized that LILA, similarly to formylated methionyl peptides in bacteria, represents a dermatophyte- and possibly fungus-specific lipid compound that allows the host phagocytes to specifically recognize fungal infection. This system would be similar to the recognition of bacteria by phagocytes via N-formylated methionyl peptides, which represent a characteristic and unique system to identify bacteria.

Arthrodermataceae↗

[LILAs (lipid-like leukocyte activators) isolated from Saccharomyces cerevisiae induce calcium mobilization in human neutrophilic granulocytes[].

Recently, we isolated some new and functionally identical panchemotactic factors (Lipid-like leucocyte activators = LILAs) from Candida albicans, Saccharomyces cerevisiae and various dermatophytes, which are chemotactic for human neutrophilic and eosinophilic granulocytes as well as for monocytes. In order to answer the question, whether human neutrophilic granulocytes express a specific receptor for LILA, we now investigated the mobilisation of the intracellular second messenger calcium within human neutrophils which were stimulated with LILA. Furthermore, LILA-mediated activation of neutrophils was subjected to desensitisation experiments with the well known neutrophil activators 5-oxo-eicosatetraenoic acid, leukotriene B4, platelet activating factor, C5a, Interleukin-8, and N-for-myl-methionyl-leucyl-phenylalanin (FMLP). The intracellular calcium concentration was measured by use of the fluorescence indicator FURA-2/AM. As a result we were able to show a significant dose-dependent increase in the intracellular calcium concentration after stimulation of human neutrophils with LILA. The desensitisation experiments revealed no cross-desensitisation between LILA and the well known stimuli. Our results show that LILA induces an intracellular calcium signal in addition to its panchemotactic activities. Therefore, calcium may act as second messenger in LILA-stimulated activation of neutrophils. Since LILA-mediated activation was maintained in the desensitisation experiments, LILA-specific receptors may be present on human neutrophils.

Calcium↗

Dynamic patterns of allergic patch test reactions to 10 European standard allergens. An analysis of data recorded by the Information Network of Departments of Dermatology (IVDK).

Insight into the dynamic time courses of patch test reactions may be useful for patch test evaluation. To put this to the proof, we have analysed the time courses of allergic patch test reactions that were filed between 1990 and 1994 by the Information Network of Departments of Dermatology in Germany (IVDK). Based on reaction strength at days 1 to 3, each allergic patch test was assigned to 1 of 5 distinct dynamic reaction patterns: crescendo, plateau, decrescendo, crescendo/decrescendo, or decrescendo/ crescendo. The frequencies of these patterns were determined for those 10 standard allergens yielding the highest numbers of allergic reactions (n between 180 and 1240), and dynamic patterns were classified as type 1 (crescendo or plateau patterns) or type 2 (other patterns). Influences of population characteristics upon the classification of patterns were evaluated by logistic regression analyses. Different frequencies of reaction patterns were found for distinct allergens. For all 10 allergens, type-1 patterns were significantly more often observed for allergic reactions assessed as clinically relevant. For 5 allergens, female sex of patients was associated with a lower frequency of type-2 patterns. A history of atopic dermatitis and the age of patients were only weakly associated with a certain classification of reaction patterns in some of the allergens. In a comparison of reaction patterns obtained with different allergens in the same population, we found that nickel sulfate elicited type 1 reaction patterns more often than fragrance mix. We conclude that the dynamic reaction patterns should be taken into account in the evaluation of patch tests. The relation of type-1 patterns to clinical relevance of the reaction needs further attention.

Adult↗

Integrity of the permeability barrier regulates epidermal Langerhans cell density.

Previous studies have shown that barrier requirements regulate epidermal liquid and DNA synthesis. In the present study, we examined the possibility that the integrity of the permeability barrier influences epidermal Langerhans cells involved with the immune response. Barrier disruption was achieved by treatment of human skin with acetone, sodium dodecylsulphate (SDS), or tape stripping, until a 10-20-fold increase in transepidermal water loss was achieved. Serial biopsies were performed 6-168 h after treatment, and Langerhans cells were complexed with anti-CD1a (Leu6) or S-100 antibodies, and visualized with an immunoperoxidase technique. Acetone treatment resulted in an increase in epidermal Langerhans cell density, reaching a maximum of 94% over control (P < 0.01) by 24 and 48 h post-treatment. Following SDS treatment or tape stripping, epidermal Langerhans cell density was increased by 100 and 175% (P < 0.01), respectively. There was a linear correlation between the degree of barrier disruption and the increase in epidermal Langerhans cell density. Studies with the Ki-S3 proliferation-associated nuclear antigen revealed a two- to threefold increase in epidermal proliferation after barrier disruption. The time curves of the increase in Langerhans cell density and the increase in epidermal proliferation were similar, suggesting that there was a coordinate regulation. In contrast with our previous studies employing patch test reactions to allergens or irritants, disruption of barrier function neither resulted in an increased dermal Langerhans cell density, nor influenced T lymphocytes (CD3+, Leu4+), macrophages (KiM8+), ICAM-1 or ELAM-1 expression in the skin. In addition, barrier disruption did not result in either dermal inflammation or epidermal spongiosis. In summary, these findings support our hypothesis that the permeability barrier influences epidermal Langerhans cell density, which is involved in maintaining an immunological barrier.

Acetone↗

Urticarial and anaphylactoid reactions following ethanol intake.

Ingestion of ethyl alcohol may be associated with a number of adverse reactions. Apart from toxicological effects, intolerance syndromes occur, which are caused by genetic or acquired defects in alcohol metabolism and are manifest clinically as flushing. In addition to these abnormalities, rare cases of generalized urticaria and anaphylactoid reactions after ingestion of ethyl alcohol have been reported, the pathogenesis of which is still a matter of debate. We describe three patients who presented with recurrent generalized urticaria, which developed within minutes of consumption of small amounts of ethyl alcohol. Common causes of chronic recurrent urticaria were excluded by case history, physical examination and laboratory investigations, and by comprehensive allergy testing. All patients produce positive prick tests with acetic acid, and developed urticaria after oral challenge with small amounts of highly purified ethyl alcohol. The symptoms are most probably caused by an intolerance to ethyl alcohol or its metabolites, whereas an allergy sensu strictu seems unlikely.

Adult↗

Evaluation of patch test results by use of the reaction index. An analysis of data recorded by the Information Network of Departments of Dermatology (IVDK).

Results of patch tests performed in 15,553 patients by 18 dermatological departments (members of the German Contact Dermatitis Research Group) and recorded by the Information Network of Departments of Dermatology (IVDK) were analysed by comparing recently defined reaction indices (RIs). The RIs studied were calculated from the numbers of allergic (a), questionable (q), and irritant (i) reactions (RI = (a-q-i/(a + q + i)), which were obtained using 13 European standard allergens. RIs were calculated for all patients and for separate subgroups defined by age, sex, history of atopic dermatitis, time of allergen exposure (1 versus 2 days), and time of patch test reading (2 or 3 days after allergen application). Higher RIs were consistently obtained when patch tests were applied for 1 day, as compared to 2 days. Readings at 3 days after allergen application resulted in higher RIs than readings after 2 days. In contrast, sex, age, and history of atopic dermatitis of patients were not found to have a consistent influence on the RIs. We suggest that reading after 3 days should be obligatory, and that allergen exposure for 1 day instead of 2 days might make patch test evaluation easier. These suggestions need to be substantiated by data on clinical relevance.

Adult↗

[Erythema necroticans migrans without glucagonoma].

Necrolytic migratory erythema is considered to be one of five well-defined paraneoplastic syndromes of the skin. An association with a pancreatic A-cell glucagonoma is commonly postulated. However, during the last years 10 cases of necrolytic migratory erythema with no evidence for glucagonoma have been published. We report on a 59-year-old woman who presented with typical clinical and histological findings of necrolytic migratory erythema. Staging and laboratory investigations gave no evidence of any neoplasia. A liver biopsy revealed chronic persisting hepatitis. Hepatocellular dysfunction was recently reported to be present concomitantly in a number of cases of necrolytic migratory erythema, suggesting a relation to the skin changes described here.

Biopsy↗