Comparison of wheat and rye flour solutions for skin prick testing: a multi-centre study (Stad 1).

BACKGROUND: Skin prick testing (SPT) is the basic method for diagnosing IgE-mediated allergies. However, skin reactivity is related to the quality of allergen extracts, which are often poorly defined for occupational allergens. OBJECTIVE: To compare wheat and rye flour SPT solutions from different producers. MATERIALS AND METHODS: Standardized SPTs were performed in seven allergy centres with wheat and rye flour solutions from four producers in 125 symptomatic bakers. Optimal cut-off levels for weal sizes were assessed with the Youden Index. Comparisons between SPT results of different solutions were made with flour-specific IgE (sIgE) as the gold standard. Sensitivities, specificities, positive and negative predictive values, and test efficiencies were calculated and compared with McNemar and chi(2)-tests. The influence of the choice of the gold standard (sIgE or challenge) test was examined for 95 subjects. Additionally, SPT solutions were analysed for protein and antigen content. RESULTS: The optimal cut-off level for all SPT solutions was a weal size of >or=1.5 mm. While differences between wheat and rye flours were small, differences between producers were important. Variability of sensitivities (0.31-0.96), negative predictive values (0.42-0.91), and test efficiencies (0.54-0.90) were higher than variations of specificities (0.74-1.00) and positive predictive values (0.88-1.00). Similar results were obtained when using challenge test results as the gold standard. Variability could be explained by the different antigen contents of the SPT solutions. CONCLUSION: There is a wide variability of SPT solutions for wheat and rye flour from different producers, mainly with respect to sensitivities, negative predictive values, and test efficiencies. Improvement and standardization of SPT solutions used for the diagnosis of baker's asthma are highly recommended.

Prediction of challenge test results by flour-specific IgE and skin prick test in symptomatic bakers.

BACKGROUND: Wheat and rye flours are among the most important allergens causing occupational asthma. Usually, the diagnosis of baker's asthma is based on inhalation challenge tests with flours. AIMS OF THE STUDY: To evaluate the relevance of flour-specific serum immunoglobulin E (IgE) and skin prick test (SPT) in the diagnosis of baker's asthma and to define flour-specific IgE concentrations and wheal sizes that allow a prediction of the outcome of challenge testing. METHODS: Bronchial and nasal challenge tests with wheat (rye) flour were performed in 71 (95) symptomatic bakers. Determinations of flour-specific IgE as well as SPTs were performed in all subjects. Analyses included the calculation of sensitivity, specificity, positive (PPV) and negative predictive values (NPV) at different IgE concentrations and different wheal sizes, and receiver-operating characteristics (ROC) plots with the challenge result as gold standard. RESULTS: Thirty-seven bakers were positive in the challenge with wheat flour, while 63 were positive with rye flour. Depending on the flour-specific IgE concentrations (wheal size), PPV was 74-100% (74-100%) for wheat and 82-100% (91-100%) for rye flour, respectively. The minimal cut-off values with a PPV of 100% were 2.32 kU/l (5.0 mm) for wheat flour and 9.64 kU/l (4.5 mm) for rye flour. The shapes of the ROC plots were similar for wheat and rye flour. CONCLUSION: High concentrations of flour-specific IgE and clear SPT results in symptomatic bakers are good predictors for a positive challenge test. Challenge tests with flours may be avoided in strongly sensitized bakers.

[Typical bacteria in an intensive care burn unit in severely burned patients and their importance with regard to mortality: retrospective study 1995 - 2004]. / Typische Bakterien auf einer Schwerbrandverletztenintensivstation und ihre Bedeutung für die Mortalität - Retrospektive Studie 1995 - 2004.

The purpose of this study was to identify risk profiles for wound infection of severely burned patients in a retrospective analysis of patients of an intensive care burn unit during 1995 - 2004. The goal of this study was to identify risk factors on wound infection in severely burned patients. Possible influences on mortality were to be discussed. Inclusion criteria of the study population was a minimum age of 18 years and a body surface area burned of at least 40 % during the time period 1995 - 2004. 912 patients were screened and 96 patients were enrolled. Logistic regression was performed to investigate factors influencing wound infection and mortality in the study population. The initially detectable bacteria in the burn wounds were Staphylococcus aureus (21.1 %), Staphylococcus epidermidis (16.2 %) and Enterococcus faecalis (16.2 %). Of all swabs taken the most frequent initial discovered bacteria were Staphylococcus aureus (18.2 %), Staphylococcus epidermidis (12.7 %), Enterococcus faecalis (12.7 %) and Escherichia coli (13.3 %). The majority of positive swabs were the burn wound followed by nose and tracheal secretion. The risk of a wound infection was more likely in the period 2000 - 2004 in comparison to 1995 - 1999 with an Odds Ratio of 0.17 (95 % KI [0.05 - 0.63], p = 0.008). Wound infection was promoted by longer hospitalization on the burn intensive care unit with an Odds Ratio of 2.62 (95 % KI [1.34 - 5.11], p = 0.005) and by bacterial detection in the unburned parts of the body with an Odds Ratio of 5.36 (95 % KI [1.30 - 22.24], p = 0.02). Death was significantly promoted by age (over 50 years) with an Odds Ratio of 11.62 (95 % KI [2.76 - 48.92], p = 0.0008), wound infection with an Odds Ratio of 0.12 (95 % KI [0.03 - 0.52], p = 0.004) and inhalation injury with an Odds Ratio of 5.95 (95 % KI [1.72 - 20.55], p = 0.005). During the study period a rise of wound infections could be notified. Promoting factors were longer hospitalization on the burn intensive care unit and bacterial detection in the unburned parts of the body. Regarding mortality, higher age, wound infection and inhalation injury were prognostic factors.

[Desmoid-type fibromatosis (aggressive fibromatosis)]. / Desmoidfibromatosen (aggressive Fibromatosen) Klinisch-pathologische Korrelationen und Differenzialdiagnose spindelzelliger fibroblastisch/myofibroblastischer Tumoren des Weichgewebes.

Desmoid-type fibromatoses (aggressive fibromatoses) represent infiltrative, locally destructively growing soft tissue tumors with a high potential for recurrence. Desmoid tumors of 33 adult patients were analysed regarding clinical and morphological aspects (sex, age distribution, site, size, mitotic rate, tumor microvessel density, surgical margins, additional radiotherapy). Possible statistical correlations were examined using log-rank-tests. No prognostic significance of tumor microvessel density was evident. A correlation between mitotic index (1 or more mitoses per 50 high power fields) and local relapse rate was notably striking, but not statistically significant (log-rank: 0.17). Additional postoperatively applied radiotherapy proved to be statistically significant to avoid local recurrences (log-rank: 0.01). The presented results may indicate an increased risk for local relapse in those desmoid-type fibromatoses which are mitotically active. Postoperative radiotherapy seems to be effective in the treatment of aggressive fibromatosis to avoid tumor recurrence. Differential diagnosis of desmoid-type fibromatosis/aggressive fibromatosis in adulthood include various fibroblastic/myofibroblastic soft tissue tumors such as nodular fasciitis, fibrosarcoma, low-grade fibromyxoid sarcoma, myofibroblastic sarcoma as well as leiomyosarcoma and soft tissue leiomyoma.

[Tenosynovial giant cell tumor]. / Tenosynovialer Riesenzelltumor Morphologische, ultrastrukturelle und immunhistochemische Befunde sowie Differenzialdiagnose riesenzellhaltiger Tumoren des Weichgewebes.

Morphological, ultrastructural, and immunohistochemical findings of 12 diffuse type-tenosynovial giant cell tumors/pigmented villonodular synovitis are presented compared to 30 localized tenosynovial giant cell tumors (giant cell tumor of tendon sheath). Diffuse-type-tenosynovial giant cell tumor is characterized by a striking vascularisation pattern composed of densely arranged thin-walled, partly slit-like and partly hyalinized small blood vessels within the papillary synovial fronds. These vessels may show abnormal structures with incompletely arranged endothelial cells/pericytes. The fibrohistiocytic tumor cells probably cause considerable compression/distortion or destruction of the small vessels which might be responsible for an increased blood deposition and massive hemosiderosis. Accompanying multinucleated osteoclast-like giant cells seemingly are recruited from circulating blood monocytes. Microhemorrhagic foci with multinucleated giant cells could be detected in 83% of diffuse-type and 67% of localized-type tumors. Apart from the described vessels, typical morphological findings in diffuse-type tenosynovial giant cell tumors included "giant" hemosiderotic granules, (at least 2-3 times the diameter of an erythrocyte) "giant" siderophages, pseudoalveolar clefts and irregularly anastomosing synovial fronds. Neither mitotic rate nor the amount of giant cells/amount of nuclei of giant cells revealed statistically significant differences between localized-type and diffuse-type of tenosynovial giant cell tumor. Immunohistochemically, the diffuse-type exhibited focal expression of CD31 (in 75% of tumors) and calretinin (in 63%) besides CD68-staining.

DNA strand breaks in the lymphocytes of workers exposed to diisocyanates: indications of individual differences in susceptibility after low-dose and short-term exposure.

Diisocyanates are chemically reactive and induce asthma, but data on genotoxic effects of diisocyanates in humans are limited. The investigation presented here used short term diisocyanate chamber exposure to study DNA strand breaks in lymphocytes of 10 healthy individuals and of 42 workers, with airway symptoms, who had previously been exposed to diisocyanates. The alkaline version of the Comet assay was used to analyse DNA strand breaks in lymphocytes. In addition, blood samples of 10 further control individuals without any exposure to diisocyanates were studied. Substances studied were 4,4'-methylenediphenyldiisocyanate (MDI, n=25), 2,4-toluenediisocynate and 2,6-toluenediisocyanate (TDI, n=5), and 1,6-hexamethylenediisocyanate (HDI, n=12), at concentrations between 5 and 30 ppb for 2 h. Lymphocytes isolated from the subjects before exposure and 30 min and 19 h after were used to evaluate DNA damage. No significant changes in DNA strand-break frequencies were measured, as Olive tail moment (OTM), either between groups or before and after diisocyanate exposure. OTM was similar in subjects with an asthmatic reaction (MDI, n=5; TDI, n=1; HDI, n=1) and in subjects without such a reaction. However, a small and susceptible group (about 10% of the individuals studied) could be identified with higher frequencies of DNA strand breaks in lymphocytes after chamber exposure. The occurrence of DNA damage in this group may be based on indirect mechanisms such as oxidative stress or apoptosis.

Changes in low molecular weight DNA fragmentation in white blood cells after diisocyanate exposure of workers.

The pathogenesis of diisocyanate-induced asthma is still largely unknown. Recently, it has been shown that thiol-redox homeostasis of human airway epithelial cells may be altered after in vitro exposure to diisocyanates. In the present study, low molecular weight (LMW) DNA fragmentation patterns in white blood cells (WBCs) were assessed on 16 industrial workers with work-related asthma, before and after chamber challenges with one of three commonly used diisocyanates in concentrations up to 30 ppb. LMW-DNA fragmentation changes were evaluated after 15 h incubation of WBCs embedded in agarose plugs in lysis buffer with or without hydrogen peroxide (H2O2). Increased LMW-DNA fragmentation occurred in WBCs taken at 30 min or 19 h after the end of the chamber challenge in both subjects with positive and in 8 of 14 subjects with negative challenges. In contrast, no change in LMW-DNA fragmentation was seen in WBCs taken at the same time intervals from 11 non-exposed controls. There was no association between changes in DNA fragmentation patterns and possible confounding factors such as age, smoking status, atopy, medication, duration of occupational exposure and period since exposure cessation. These results indicate that diisocyanate exposure can induce DNA fragmentation. Similarities in the increased amounts of WBC LMW-DNA fragments following diisocyanate exposure with the DNA fragmentation after plugs lysis in buffer with H2O2 support the hypothesis that diisocyanates change the intracellular redox steady-state. Whether this effect plays any role in isocyanate-induced asthma has to be investigated in larger epidemiological studies.