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Biomedical subjects

U Wahn

Publications and source records attributed to U Wahn.

At least 163 records · Page 9Linked to original sources
PubMed1996

[Comparison of serum concentrations of once and twice daily administration of ultra-retard theophylline in school children with bronchial asthma].

It was the aim of our study to find out whether once-daily administration of an ultra-retard preparation is meaningful also during childhood if compared to twice-daily application. To this end we examined 11 children (6 girls, 5 boys) between 7 and 16 years of age (median 12 years) who were suffering from bronchial asthma. The same theophylline daily dose was administered for 10 days each either as a single dose in the evening (20.00 hrs) or subdivided into two single doses (9.00 and 20.00 hrs). Dosage was according to age between 11 and 24 mg/kg body weight and day. The median values of blood serum concentration of theophylline of the once-daily or twice-daily administration in the "steady state" did not show any significant difference in the course of the 24-hour observation. The maximum effective concentration was attained after 12 hours in case of the once-daily application and after 8 hours with the twice-daily application. Summing up, our data indicate that good control of asthma bronchiale can be achieved even with once-daily administration of an ultra-retard preparation also in childhood. With both regimens the blood serum concentrations showed a satisfactorily low variability over 24 hours.

Adolescent↗
PubMed1995

Pancreatic insufficiency and pulmonary disease in German and Slavic cystic fibrosis patients with the R347P mutation.

Cystic fibrosis (CF) is caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) that codes for a cAMP-regulated chloride channel. The R347P is a missense mutation located within the first membrane spanning domain (MSD1) of the CFTR protein. This mutation occurs with an overall worldwide frequency of about 0.2%. The patients, originally described with this mutation were compound heterozygotes with the delta F508 mutation and had a very mild course of CF, suggesting that R347P, similar to other missense mutations affecting the MSD1 domain, causes a mild phenotype. We report here a group of 19 CF patients with the R347P mutation of German, Bulgarian, Czech, and Slovak origin, including two homozygotes. Most patients presented with early disease onset, pancreas insufficiency (PI), and early pulmonary involvement, suggesting that this mutation can lead to a severe course of CF. Most R347P alleles in the group studied share a common polymorphic haplotype. In addition, these analyses gave evidence for recurrence of the mutation in two CF patients of German and Czech origin.

Cystic Fibrosis↗
PubMed1995

Two cases of pulmonary tuberculosis presenting with unilateral pulmonary hyperinflation in infancy.

UNLABELLED: Two infants with recurrent obstructive symptoms attracted attention because of massive radiologically detected unilateral pulmonary hyperinflation. Further diagnostic procedures including bronchoscopy, revealed a pulmonary tuberculosis with lymph nodes encroaching on the bronchi. Steady improvement of clinical symptoms and hyperinflation was noted under combined antituberculotic therapy including systemic steroids. CONCLUSION: Our two cases demonstrate that the differential diagnosis of unilateral pulmonary hyperinflation and wheezing in infancy should consider valvular stenosis by encroaching lymph node due to pulmonary tuberculosis.

Bronchi↗
PubMed1995

Evaluation of the child with suspected primary immunodeficiency.

Infections are one of the major causes for visits to paediatricians. Most children recover without sequelae, untreated or if treated properly, and develop specific immunity towards the challenging microorganisms (mostly viruses). There is a small proportion of children however, with unusual frequent, severe, chronic, recurrent or opportunistic infections in whom an underlying immunodeficiency must be suspected. Based on current knowledge about the major types of congenital immunodeficiencies this review suggests a diagnostic approach to these children. Early evaluation will allow early identification of affected children and, subsequently, lead to proper treatment before devastating infections cause irreversible organ damage.

Child↗
PubMed1995

Individual time-courses of ECP and EPX during allergen provocation tests in asthmatic children.

To study the time-course of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) during bronchial allergen provocation, we investigated 32 asthmatic children sensitive to house-dust mites as well as 6 non-atopic young adult controls. In all subjects, allergen challenges were performed with house dust mite extracts of Dermatophagoides pteronys-sinus or Dermatophagoides farinae. Blood samples were taken at regular intervals during the 24-h observation period. The individual time-courses of ECP and EPX revealed different characteristic groups of patterns: (1) an isolated early serum peak of both mediators during or within the first 60 min after provocation (2) an early plus a late peak (3) an isolated late peak 12 h after provocation (4) an isolated late peak 24 h after provocation, and (5) no significant variation during the 24-h observation period. The early peak could be due to short-term changes in eosinophil activation, while late peaks may reflect eosinophil proliferation, recruitment, subsequent priming and enhancing of the propensity to release their proteins. ECP and EPX showed a corresponding parallel time-course in nearly all challenges, with EPX-concentration exceeding that of ECP. There was no correlation between ECP/EPX serum concentrations and clinical parameters such as lung function data. From our results we conclude that the striking groups of time-courses of ECP/EPX serum concentration indicate different uniform patterns of eosinophil activation during allergen challenge-but do not predict clinical outcome of provocation. The role of the eosinophil in early asthmatic reactions remains to be established in further studies.

Adolescent↗
PubMed1995

Soluble interleukin-4 receptor in atopic children.

The levels of natural soluble interleukin-4 receptor (shuIL-4R) were determined in the peripheral blood of 29 children with stable asthma, 10 children with asthma and acute respiratory infection, 11 healthy children with acute airway infection and 31 healthy controls. Healthy controls revealed the highest levels (median 1,082 pg/ml, range 524-1,900 pg/ml); which differed significantly from levels obtained with the blood of stable asthmatics (p < 0.01, median 658 pg/ml, range 329-1288 pg/ml), patients with asthma and acute respiratory infection (p < 0.01, median 663 pg/ml, range 0-1,250 pg/ml) and patients with respiratory infection alone (p < 0.01, median 674 pg/ml, range 466-1,110 pg/ml). In contrast, there was no significant difference in shuIL-4R content of cord blood obtained from newborns with a high or low risk of atopy. Additional analysis of interleukin-4 receptor (huIL-4R) on cultured lymphocytes from 13 stable asthmatic children and 14 healthy children indicated higher expression on CD4 cells (p < 0.05, median 2.2%, range 0.8-7.8%) compared to healthy controls (median 1.3%, range 0.7-3.3%). Therefore, diminished shuIL-4R concentrations in plasma may be related to inflammatory states but not specifically to atopy. The results support the notion that huIL-4R expressed on the cell surface may be regulated differently from the soluble form.

Acute Disease↗
PubMed1995

Therapeutic interference with interferon-gamma (IFN-gamma) and soluble IL-4 receptor (sIL-4R) in allergic diseases.

Allergic sensitization is controlled by CD4+ T cells. A complex interaction between antigen-presenting cells, T- and B-cells results in the production of (allergen) specific IgE. Analysis of the lymphokine profile of lymphocytes from patients with bronchialasthma and atopic dermatitis revealed an imbalance in cytokine production. An enhanced production of IL-4 was accompanied by low or absent amounts of IFN-gamma. Since both cytokines play a central role in the regulation of IgE, it was examined whether therapeutic interference on the level of cytokine production may provide an useful tool to alter lymphocyte functions in allergic diseases. Two different model systems were employed to study the effects of soluble IL-4R (sIL-4R) under in vitro and in vivo conditions. (1) A mouse model system for allergic sensitization and increased airways responsiveness (AR) was employed to examine whether in vivo treatment with recombinant murine sIL-4R may prevent the development of allergic sensitization. It was found that local treatment through the airways and the lung as carried out by aersolization of the receptor offered a route of application that prevented the development of allergen-induced and allergen-dependent immediate hypersensitivity responses including the development of increased AR. (2). The in vitro effects of humans sIL-4R on functions of mononuclear cells prepared from two patients with most severe atopic dermatitis were examined. Incubation of lymphocytes with allergens in the presence and absence of sIL-4R indicated that the soluble receptor suppressed allergen-induced lymphocyte proliferation and allergen-dependent IgE, IgG and IgM production. In addition a complete suppression of allergen-specific IgE production was detected in the presence of sIL-4R. These data suggest that sIL-4R may provide a useful drug to modify lymphocyte-dependent immune functions in allergic diseases.

Allergens↗
PubMed1995

Activation of bronchoalveolar lavage T lymphocytes and clinical, functional and radiological features in sarcoidosis.

Previous studies on the relationship between activated BAL T lymphocytes and clinical features in sarcoidosis revealed controversial results. We determined lavage lymphocytes, T lymphocytes, activated T lymphocytes, helper, suppressor and natural killer cells in 50 patients with pulmonary sarcoidosis and compared the results with clinical findings, serum angiotensin converting enzyme (ACE), the radiological pattern and lung function data (vital capacity [VC], total lung capacity [TLC], FEV1, transfer coefficient KCO and arterial-alveolar oxygen difference [AaDO2] during exercise). Patients with erythema nodosum (n = 7) showed a lower proportion of activated T lymphocytes (p < 0.05) and lymphocytes (p < 0.01) than the other patients. There was a significant correlation between activated T lymphocytes and AaDO2 during exercise (r = 0.49, p < 0.001), and an inverse correlation was seen between activated T lymphocytes and VC or TLC (r = -0.35 and r = -0.36, p < 0.01). We conclude that the percentage of activated BAL T cells may be related to the degree of parenchymal involvement as expressed by functional disturbance.

Adult↗
PubMed1994

The role of eosinophils and eosinophil cationic protein in monitoring oral challenge tests in children with food-sensitive atopic dermatitis.

To investigate the role of peripheral blood eosinophils and eosinophil cationic protein as parameters in monitoring oral food challenges, we monitored 25 infants and children with atopic dermatitis for up to 48 hours after 47 placebo-controlled oral food challenges with cow's milk, hen's egg, cow's milk and hen's egg, or placebo for up to 48 hours. Six healthy young nonatopic adult volunteers served as control subjects. Compared with baseline values, peripheral blood eosinophils decreased significantly immediately after clinical reaction in positive challenges (p < 0.0004), independent of the kind of reaction. Eosinophil cationic protein increased significantly 8 hours after provocation, with a maximum at 24 hours (p < 0.03). This increase was predominantly related to eczematous reactions (p < 0.005). Blood sampling immediately after clinical reaction (for eosinophils) and at 24 hours (for eosinophil cationic protein) seems to be useful in monitoring oral food challenges in children with atopic dermatitis.

Adolescent↗
PubMed1994

Thymosin alpha 1 effects, in vitro, on lymphokine-activated killer cells from patients with primary immunodeficiencies: preliminary results.

In patients with primary immunodeficiencies the role of natural killer (NK)- and lymphokine (IL-2)-activated killer (LAK)-cells is not yet satisfactorily established. Using a clonogenic assay with K562 leukemia target cells, we studied their NK- and LAK-cell activity in vitro. Moreover, the effect of thymosin alpha 1 (T alpha 1) on LAK-cell activity was studied in 11 patients with different immunodeficiencies. The results were compared with data of healthy controls (n = 11) and cord blood samples (n = 6). Common variable immunodeficiency patients demonstrated a mean LAK-cell activity of about 65% of normal controls and cord blood samples. The moderately reduced LAK-cell activity was not affected by T alpha 1. In the immunodeficient other patients, low levels of LAK-cell activity with a mean value of 10% of normal controls were seen. The mean LAK-cell activity could be improved by T alpha 1: three patients showed an improvement of their LAK-cell activity up to 25-30% after T alpha 1 administration in vitro, but in one case T alpha 1 was without any effect. Analysis of the expression of the surface markers CD8, CD16, CD57 and CD8/CD57 revealed that only CD16 positive lymphocytes were significantly less in immunodeficient patients. We found a linear correlation between LAK-cell activity and CD8/CD57 double positive lymphocytes in all patients. Our results demonstrate that suppressed LAK-cell activity from immunodeficient patients can be individually improved by T alpha 1. Further in vivo studies should evaluate thymic peptide immunotherapy for individual immunodeficient patients.

Adolescent↗
PubMed1994

Discrepancies between in vitro and in vivo tests for house dust mite allergy: in domestic exposure a better predictor than sensitization?

We subjected seven asthmatic children to two bronchial allergen challenges, first with an extract from the house dust mite Dermatophagoides pteronyssinus (Der p) and then Dermatophagoides farinae (Der f), or vice versa. All children had elevated specific serum IgE to both species as well as reactions by crossed radioimmuno/electrophoresis (CRIE) to both group I and II allergens from both species. Immunoabsorption and subsequent analysis by CRIE showed a considerable concentration of serum IgE with specificity for epitopes common to the two species of house dust mite. Home dust sampling established that all children were exposed to Der f and only two to Der p. On bronchial provocation tests, all responded to Der f with an immediate reaction and five with a late reaction, only three of seven showed an immediate response to Der p, with four of the seven showing a late reaction. Our data could indicate that the local allergic immune reaction in the respiratory tract is sustained by ongoing exposure, and may thus have a different species specificity than the response reflected in the serum. In conclusion, our data indicates a lack of association between in vitro and in vivo tests for house dust mite allergy, which supports the continuing need for monitoring current clinical sensitization by allergen provocation tests and by measuring domestic exposure to the corresponding allergen. Extended studies are needed to support our findings.

Allergens↗
PubMed1994

Twenty-four-hour time course of eosinophil granule proteins ECP and EPX during bronchial allergen challenges in serum of asthmatic children.

To study in vivo monitoring variables for bronchial allergen challenges, we investigated the time course of the eosinophil granule proteins, eosinophil cationic protein (ECP) and eosinophil protein X (EPX) after allergen provocation in serum. Thirty-two asthmatic children sensitive to house-dust mites and six healthy young adult controls were challenged by bronchial allergen provocations with Dermatophagoides pteronyssinus and D. farinae. Blood samples were taken at regular intervals up to 24 h. Base-line concentrations of ECP (P < 0.004), EPX (P < 0.002), and eosinophils (P < 0.001) were found to be increased in asthmatic children, as compared with healthy controls. ECP and EPX concentrations showed a uniform pattern with two characteristic features: 1) a rapid increase for both mediators up to 30 min after provocation over base-line values (P < 0.0001 and P < 0.001), followed by a rapid decrease nearly to base-line values in the next 30 min; and 2) a steady increase for ECP and EPX up to 10 h (P < 0.02 and P < 0.01), and even higher levels at 24 h, after challenge (P < 0.002 and P < 0.003). We conclude that although eosinophils are activated in asthmatic children after bronchial allergen challenge, ECP and EPX concentrations are not suitable monitoring variables. Base-line eosinophils seem to predict the occurrence of a late-phase asthmatic reaction after allergen provocation.

Adolescent↗
PubMed1994

Specification and quantitation of circulating immune complexes in the serum of patients with active pulmonary sarcoidosis.

BACKGROUND: Circulating immune complexes can be elevated in serum samples of patients with sarcoidosis and are associated with disease activity, but their diagnostic significance is not understood. METHODS: The different classes of circulating immune complexes containing immunoglobulin A, G, or M, and the content of complement in circulating immune complexes (polyethylene glycol precipitation) as well as levels of complement binding circulating immune complexes (complement binding assay) were determined in 19 patients with active, untreated pulmonary sarcoidosis. The results were compared with other parameters in the serum (soluble interleukin 2 receptor, angiotensin converting enzyme, immunoglobulin A, G, and M) and the bronchoalveolar lavage fluid (lymphocytes, helper cells, suppressor cells, activated T cells), and with radiological stage and functional parameters (FEV1, vital capacity, total lung capacity, transfer coefficient (KCO), and the alveolar-arterial oxygen difference during exercise). RESULTS: In all patients circulating immune complexes could be detected by polyethylene glycol precipitation and were similar to control subjects. The content of C1q in circulating immune complexes was higher than in controls, yet in all but one of the cases was still within normal limits. In contrast, elevated levels of complement binding circulating immune complexes were found in 67% of the patients. No correlation was seen between circulating immune complexes and any of the other parameters in the serum, bronchoalveolar lavage fluid, or lung function values. No differences were found between radiological type I and II presentations of sarcoidosis. CONCLUSIONS: The complement binding assay showed a much higher sensitivity for the detection of circulating immune complexes in active pulmonary sarcoidosis than the polyethylene glycol precipitation method. As there was no correlation between levels of circulating immune complexes and other parameters of the disease they are probably not useful for the assessment of disease activity.

Adult↗