Biomedical subjects
Publications and source records attributed to U Wahn.
We present 2 cases of children with Niemann-Pick disease type B, and surprisingly with reticular lung infiltrations, although otherwise healthy in terms of pulmonary manifestation. Finding such reticular infiltrations should lead one to think of the possibility of metabolic storage disease.
Glycosphingolipids (GSLs) are physiological membrane components known to modulate various cellular functions. In order to study their influence on basophil mediator release washed leukocytes obtained from allergic asthmatics and nonatopics were preincubated with varying concentrations of different GSLs. Cells were washed and stimulated with anti-IgE, allergen, and calcium ionophore A23187. None of the GSLs induced mediator release by itself. Preincubation with the acidic gangliosides GM2, GM3, and GD1a significantly enhanced the release of both mediators when stimulated with anti-IgE or allergen but not with calcium ionophore A23187. Highest enhancement was seen with ganglioside GM2. Mediator release was higher in asthmatics than in nonatopics. The acidic galactosylceramide-sulfate (sulfatide) showed a significantly enhanced mediator release as well, whereas the neutral GSLs lactosyl ceramide and asialo GM2 did not influence mediator release. It is concluded that IgE receptor-dependent mediator release could be modulated by acidic GSLs.
To study the usefulness of urinary 1-methylhistamine and serum tryptase concentration as monitoring parameters in clinical settings, we investigated 32 children with atopic dermatitis and suspected food allergy during oral food challenges with eggs and cow's milk. Urinary 1-methylhistamine (MH) excretion increased significantly within 1 h after positive oral food challenges (p < 0.006), but showed considerable variation in negative challenges. MH seems to be a sensitive parameter (92.8%), but its specificity is insufficient (37.7%). In the group of 16 positive oral food challenges serum tryptase concentration increased significantly (p < 0.02) directly after provocation and remained elevated up to 2 h after provocation. No variation was observed in negative challenges or nonatopic controls. Serum tryptase concentration seems to be specific for marked clinical reactions after oral food challenges (100%), but its sensitivity was low (25%) and not superior to evaluation by clinical means. We conclude that, despite positive results for the group of children, MH and serum tryptase concentrations are not useful parameters for monitoring oral food challenges in an individual child due to insufficient sensitivity and specificity.
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Na+/Mg2+ antiport and Na(+)-independent Mg2+ efflux were investigated in erythrocytes of 41 patients with cystic fibrosis and 26 controls. Na(+)-independent Mg2+ efflux was unchanged in cystic fibrosis, but a significantly increased activity of Na+/Mg2+ antiport was detected (control: 0.16 +/- 0.02, cystic fibrosis: 0.39 +/- 0.06, Mg2+ efflux, mmol/30 min x 1 cells, mean +/- SEM, p < 0.01). An increased activity of Na+/Mg2+ antiport was only found in patients with severe clinical symptoms. There was no correlation of the increased Na+/Mg2+ antiport to the dF508 genotype. In a patient with increased Na+/Mg2+ antiport, the capacity of this transport system was unchanged 14 weeks after double lung transplantation but reached control values after 53 weeks. The sweat of cystic fibrosis patients with severe clinical symptoms showed a significantly increased Mg2+ concentration (control (n = 12): 0.053 +/- 0.08, cystic fibrosis (n = 9): 0.123 +/- 0.016 mmol/l, mean +/- SEM, p < 0.001).
Efficacy of preventive chemotherapy in tuberculosis-infected children depends to a great extend on medical compliance and drug tolerability. Two new short-course chemoprevention-regimes of tuberculosis--four months Rifampin (A) and two months Rifampin plus Pyrazinamide (B)--were compared with the well established regimen of six months Isoniacid (C). 150 children (mean age 3.6 years with Tb conversion) were randomly allocated to these three regimens. 13 patients were non-compliant, in terms of interview, urinary INH-test strips, urine colour and prescription frequency: 7 in group C and 3 in group A and B, respectively. Adverse effects were observed in 5 patients: 3 in group C and 1 in group A and B. 1 child (group B) developed tuberculosis two years after stopping short course chemoprevention. Good compliance (94%) as well as neglectable risks of adverse effects (2%) justify further controlled studies to evaluate the efficacy of short course chemoprevention in childhood.
Sensitization to indoor allergens like house-dust mite and animal dander as well as outdoor allergens like grass and tree pollen play an important role in the development to atopic airway disease, i.e. atopic rhinitis and conjunctivitis and allergic asthma. Studies on emergency room patients in the US showed that the sensitization to cat dander and house-dust mite Dermatophagoides represented risk factors for acute attacks of asthma. However, irrespective of the inheritance of atopy, disease of specific organs and expression of symptoms remain highly variable and are likely to depend on a multiplicity of environmental factors, the most important of which is likely to be the level of exposure to the sensitizing allergen. There is increasing evidence that exposure to potential allergens early in life is important. Concentrations and timing of the exposure seem fundamental. The elimination of allergens in households of atopic individuals is crucial in a prophylaxis and therapy. There have been several publications on mite allergen elimination procedures; a lot of them are uncontrolled, and allergen reduction is not significant. This article tries to compare trials reporting of improvement of clinical symptoms and significant reduction of indoor allergens with those trials which did not achieve significant results.
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The chest radiograph of a 35-year-old man with fatigue, exertional dyspnoea and haemoptyses revealed a cavity in the left upper lobe and a shrunken left lung with radiolucency greater than that on the right. Acid-fast rods in sputum were identified as Mycobacterium kansasii on culture. Scintigraphy showed a 9% residual perfusion on the left and abnormal ventilation, compatible with Swyer-James syndrome. This had favoured the development of a mycobacterial infection. There was also a decrease in ciliary function (rate of 4-7 Hz, normal: 10-11). Treatment, begun when tuberculosis had been suspected, was after sensitivity tests changed to a combination of rifampicin (600 mg), ethambutol (1600 mg) and protionamide (500 mg) daily. There was marked regression of the findings within 4 weeks, but treatment was prematurely stopped after 11 months. Two years later there was a recurrence which again responded well to the same drug regimen with additional sulphamethoxazole (1600 mg/d).
A microfiberglass-based histamine assay (HRM) was compared with an automated fluorometric histamine assay (HRA). Twenty-four subjects with and 24 without a case history (CH) of milk and/or egg allergy were tested by HRM and HRA, skin prick test (SPT), and specific serum IgE (RAST). Six different concentrations of milk, egg, and anti-IgE were used to stimulate washed leukocytes (250 microliters for HRA) and whole blood samples (25 microliters for HRM) in parallel. When we compared scores representing basophil sensitivity, correlation coefficients (rs) were positive (r(anti-IgE) = 0.88, r(egg) = 0.95, r(milk) = 0.88, P < 0.001), but no significant correlations were found after exclusion of the negatives in both tests. In some individual dose-response curves, the scores obtained by HRM were shifted to higher allergen and anti-IgE concentrations. A high degree of concordance was found in positive and negative responses between the two tests: anti-IgE 91%, egg 92%, milk 86%. Finally, we found a good concordance between, on one side, HRM and, on the other, CH, SPT, and RAST (HRM vs. CH/SPT/RAST): egg 92/82/82%; milk 89/74/67%. We conclude that HRM is in good qualitative, but poor quantitative, agreement with the autoanalyzer-based fluorometric histamine assay.
From our data we conclude, that the determinations of ECP and EPX do not add any useful information as monitoring parameters for bronchial allergen challenge tests. In contrast, eosinophils and eosinophil cationic protein may deserve further study as potentially useful monitoring parameters for oral food challenges in patients with food related atopic eczema.
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In order to identify newborns at risk for atopic diseases, we developed a family questionnaire and selected specific answers which were suitable to identify atopic family members. The validity of the questionnaire was evaluated by the Phadiatop test results of 793 mothers and 353 fathers. As both screening instruments do not measure the same, the Phadiatop test identifies sensitization to inhalant allergens and the history reflects the clinical manifestation of atopic disease, the agreement between sensitization and manifestation is incomplete. Sensitivity and specificity of the questionnaire screening conditions to reproduce the Phadiotop test result was 64% and 84% for mothers, and 58% and 88% for fathers, respectively. The relative risk for lifetime prevalence of atopic manifestations in Phadiatop positive over negative mothers was calculated to be 3.88 (95% confidence interval = 3.12 to 4.81), and for Phadiatop positive over negative fathers to amount 4.84 (95% confidence interval 3.25 to 7.23). A few relevant answers of 20 were identified by logistic regression analysis to predict the Phadiatop test result nearly, as well as the total questionnaire.
In order to study cell activation in peripheral blood on bronchial allergen provocation up to 24 h, we investigated 32 asthmatic children, sensitive to house-dust mites. Six healthy young adult volunteers served as controls. Lymphocyte subsets (CD3, CD19, CD4, CD8) and activation markers (CD25-T, HLADR-T, CD23) in peripheral blood as well as soluble IL2-R and soluble ICAM-1 in serum were evaluated. In terms of clinical reaction, 23 children exhibited a DAR, 6 an EAR, 6 a LAR and 3 children did not show a bronchoconstrictor response to allergen challenge with house-dust mite extract (NAR). In comparison to controls, asthmatic children showed a significantly higher expression of CD23 on B-lymphocytes (p < 0.05). Other subsets were in the same range in both groups. After provocation there was a significant increase of CD4/CD8-ratio only in asthmatic children. Serum levels of sIL2-R were significantly higher in asthmatic children compared to controls at baseline as well as at 12 and 24 h after provocation, without variation during observation period. No differences were noted for sICAM-1. Our results confirm the hypothesis that lymphocytes, as important cells in regulation of allergic immune response, are recruited into peripheral blood under allergen challenge conditions in sensitized asthmatic children.
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Alpha 1-proteinase inhibitor (alpha 1-PI) has been demonstrated to suppress mitogen-induced lymphocyte response in vitro. To evaluate the effect of intravenous application of human alpha 1-PI (Prolastin HS) on cellular immunity, we determined total lymphocyte count, lymphocyte subsets and lymphocyte response to concanavalin A, before and 24 h after infusion of 60 mg.kg-1 body weight alpha 1-PI in eight patients with homozygous alpha 1-PI deficiency (PiZ phenotype). The results were compared with two blood samples from seven healthy controls. After infusion, serum alpha 1-PI levels were increased from 0.98 +/- 0.24 to 2.68 +/- 0.51 g.l-1. No significant differences were found for total lymphocyte count, lymphocyte subsets and lymphocyte response between both groups in both samples. Maximum 3H-thymidine incorporation before and after infusion showed no significant difference; the same was true for the two control samples. However, additional incubation in vitro with alpha 1-PI 5 g.l-1 led to a significant (p < 0.03) decrease of lymphocyte proliferation in samples after infusion. Our data indicate that alpha 1-PI substitution therapy does not lead to a major suppression of lymphocyte response to concanavalin A in PiZ individuals in vivo, although a suppressive effect was found after additional in vitro incubation with alpha 1-PI.
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BACKGROUND: Questions on asthma symptoms like "wheezing" or "whistling in the chest" must be easily understood by the general population. In preparation of a standardized German questionnaire we investigated, how children with asthma and their parents would describe symptoms during an asthma attack. METHODS: From June until December 1991, 72 children aged 13-15 years, and parents of 138 children aged 7-15 years with diagnosed asthma, where interviewed whilst they visited the outpatient department of the universities of Berlin, Leipzig, and Munich. The parents and children were asked to answer a questionnaire which included a list of adjectives and descriptions proposed to describe the child's breathing during an asthma attack. The items included descriptions which have been used on German questionnaires, others which we considered possibly useful, anc control items which we considered inappropriate. Parents and children were asked to rate on scales how much they would agree or disagree to the proposed items as possible descriptors. Descriptive and cluster analyses revealed those descriptions which received the best ratings. RESULTS: The rating was rather independent of the sex of the child, the respondent (child vs parent) and the severity of attacks, but differences between regions were observed. CONCLUSION: The verbal descriptors with the best rating will be used for the wording of a German questionnaire on asthma symptoms.