Absolute beta-catenin concentrations in Wnt pathway-stimulated and non-stimulated cells.

The intracellular level of the proto-oncoprotein beta-catenin is a parameter for the activity of the Wnt pathway, which has been linked to carcinogenesis. The paper introduces a novel sandwich-based ELISA for the determination of the beta-catenin concentration in lysates from cells or tissues. The advantages of the method were proven by determining beta-catenin levels in cell lines and in cells after activation of the Wnt pathway. Analysis revealed high beta-catenin concentrations in the cell lines HeLa, KB, HT1080, MCF-7, U-87 and U-373, which had not been described before. Beta-catenin concentrations were compared in HEK293 and C57MG cells after activation of the Wnt pathway. The beta-catenin concentrations increased by different factors depending on whether the Wnt pathway was activated by incubation with LiCl or with Wnt-3a-conditioned medium. This finding indicated that the beta-catenin level depends on the way and level of Wnt pathway activation. The quantitative analysis of beta-catenin in colorectal tumours revealed high beta-catenin levels in tumours with truncating mutations in the APC gene.

The treadmill exhausting test is not suitable for screening of growth hormone deficiency!

BACKGROUND/METHOD: We compared the growth hormone response to a modified exercise test--the treadmill exhausting test--to pharmacological stimulation tests in 77 children with short stature. Each child underwent the treadmill test to individual exhaustion and at least one pharmacological test for GH stimulation. To determine the point of individual exhaustion, the heart rate, workload and oxygen consumption were measured. RESULTS: The mean +/- SEM peak GH concentration (ng/ml) in 47 small, normally growing children (group 1) was 16.1 +/- 1.3 in the pharmacological tests vs. 5.0 +/- 0.6 after a treadmill exhausting test. Thirty children with GH deficiency (group 2) had mean +/- SEM peak GH concentrations (ng/ml) of 5.5 +/- 0.5 in the pharmacological tests and 4.1 +/- 0.7 after physical exercise. The groups differed significantly in the pharmacological tests (p < 0.001) but not in the exhausting test. We found a 90% sensitivity but only a 11% specificity for the treadmill exhausting test compared to the diagnosis obtained by pharmacological testing. CONCLUSION: We do not recommend the treadmill exhausting test in clinical practice of pediatric endocrinology at all.

A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children.

BACKGROUND: Increased levels of total serum IgE are a strong risk factor for the development of asthma. IgE is also involved in host defenses against parasites and fungi. Linkage of total serum IgE with markers located close to the 3 Mb cluster of cytokine genes in chromosome 5q31 has been reported. IL-4 or IL-13 are regarded as essential for IgE synthesis. OBJECTIVE: We tested whether polymorphisms in the IL-13 gene might explain the linkage between chromosome 5q31 and total serum IgE levels. METHODS: We used denaturing HPLC to detect polymorphisms in overlapping PCR fragments of the IL-13 gene including promoter and 3' untranslated regions. After sequencing was performed to identify the locations of the polymorphisms, PCR and primer-induced restriction site assays were used to genotype subjects in 3 unselected populations. RESULTS: We report here 7 polymorphisms (6 novel) in IL-13. Four of these polymorphisms are tightly linked to a variant in the terminal portion of the coding region of the gene that results in a predicted amino acid change in residue 130 (Arg130Gln). The Gln form is strongly associated (P =.000002) with increased serum IgE levels in 3 different populations comprising a total of 1399 children. Two additional polymorphisms in the promoter region of IL-13 are more loosely linked to Arg130Gln and are also less significantly associated with total serum IgE levels. CONCLUSION: These data suggest that the Arg130Gln polymorphism in IL-13, or others in close linkage with it, is associated with the development of the elevated serum IgE phenotype.

Prevalence of respiratory and atopic disorders among children in the East and West of Germany five years after unification.

Living conditions in eastern Germany have changed rapidly since unification in 1990 and little is known about how these changes affect the prevalence of atopic diseases. This study describes methods and prevalences of a large epidemiological project investigating determinants of childhood asthma and allergies in eastern (Dresden and Leipzig) and western (Munich) Germany in 1995/1996. Community based random samples of 9-11 yr old children in Dresden (n=3,017) and Munich (n=2,612), and of 5-7 yr old children in Dresden (n=3,300), Leipzig (n=3,167) and Munich (n=2,165) were studied by parental questionnaires, bronchial challenges with hypertonic saline, skin examination, skin-prick tests, and measurements of specific and total serum immunoglobulin (Ig)E using Phase II modules of the International Study of Asthma and Allergies in Childhood (ISAAC). In 9-11 yr old children, the prevalence of physician diagnosed asthma (7.9% versus 10.3%; p<0.01) and bronchial hyperresponsiveness (15.7% versus 19.9%; p<0.05) was lower in Dresden than in Munich. No difference between Munich and Dresden was observed in the prevalence of diagnosed hay fever, skin test reactivity to > or = 1 allergen, and increased levels (>0.35 kU x L(-1)) of specific IgE against inhalant and food allergens. Symptoms and visible signs of atopic eczema tended to be more prevalent in Dresden. Similar East-West differences between the three study areas were seen in the younger age group. These findings are in line with recently observed increases in the prevalence of hay fever and atopic sensitization, but not of asthma and bronchial hyperresponsiveness, among 9-11 yr old children in Leipzig.

Increasing prevalence of hay fever and atopy among children in Leipzig, East Germany.

BACKGROUND: Several surveys in children and adults have shown significantly lower prevalences of asthma and allergic diseases in eastern Europe than in western countries. In the former East Germany tremendous changes towards western lifestyle have occurred since unification. The aim of this survey was to investigate time trends in the prevalence of asthma and allergic diseases among children living in the eastern part of Germany. METHODS: In 1995-96, 2334 (87.5%) schoolchildren in Leipzig participated in a cross-sectional study that used the same methods as a previous survey done shortly after the fall of communism in 1991-92. A self-administered questionnaire was distributed to the parents. Children underwent cold-air challenge and allergy skinprick tests to six common aeroallergens. FINDINGS: The prevalence of hay fever (2.3% [34/1454] vs 5.1% [115/2252], p<0.0001) and atopic sensitisation (19.3% [252/1303] vs 26.7% [434/1624], p<0.0001) increased significantly between 1991-92 and 1995-96. However, there was no significant change in the prevalence of asthma, asthma-related symptoms, or bronchial hyper-responsiveness. INTERPRETATION: These findings suggest important differences in the development of atopic disorders. The children were born about 3 years before unification and were therefore exposed to western living conditions only after the third birthday. Thus, factors operating very early in life may be particularly important for the acquisition of childhood asthma, whereas the development of atopic sensitisation and hay fever may also be affected by environmental factors occurring beyond infancy.

Sulthiame-associated mild compensated metabolic acidosis.

Sulthiame is effectively used in the treatment of benign and symptomatic focal epilepsy in children. Hyperventilation as a symptom is a well known adverse effect of the drug. Alterations of the acid-base equilibrium have been described for the drug, however, very infrequently only in adults without a detailed evaluation of the disorders status. The case presented here demonstrates a mild compensated metabolic acidosis in a child which, for the first time, is described using the methods of complete blood gas and electrolytes analysis.

Psychosocial characteristics of asthma.

The objective of this study was to compare psychosocial characteristics of children with asthma and children with bronchial hyperreactivity with those of normal children. A population-based study of 2634 children (mean age, 10 years) was carried out. Pulmonary function tests of children were performed in children before and after cold air hyperventilation challenge to determine bronchial hyperreactivity. Parental assessment of children's behavior was evaluated with 15 questions about school/learning habits, level of activity, communication/affection, and sleeping patterns. A factor analysis was performed and the factor loading adjusted for confounders compared in the different groups. Asthmatic children sleep less well than normal and hyperreactive children (p < 0.001). Unexpectedly, however, all other single items did not differ significantly. As a result of the factorial analysis we obtained two factors. On the first factor, measuring school behavior and learning, there was a small difference between asthmatic and normal children, which could not be found on the second factor indicating activity and communication. We conclude that psychosocial differences of asthmatic children are less remarkable than expected. As a result of the examination of the hyperreactive children it is likely that asthmatic children are influenced more by secondary psychosocial factors than by any primary effect of asthmatic disease.

[Schimmelpenning-Feuerstein-Mims syndrome and its neurologic manifestations. 6 personal cases and review of the literature]. / Das Schimmelpenning-Feuerstein-Mims-Syndrom und seine neurologische Symptomatik. 6 eigene Kasuistiken und Literaturübersicht.

The Schimmelpenning-Feuerstein-Mims-syndrome includes deformities and dysplasias of the skin, eyes, brain, skeleton, and heart. It may result from a malformation of the ectodermal and mesodermal blastoderm in the third week of gestation. We here report on 6 patients who presented between 1977 and 1993 in comparison with those cases in the literature. All children presented neurologic symptoms. The major symptom was a linear epidermal nevus. In addition we found mental retardation, convulsions, asymmetries of the cranial structures or dilated cerebral ventricles ipsilateral to the nevus. One child had a defect of the skull and scalp, a symptom not previously mentioned in the literature. Our patients exhibited a wide phenotypice spectrum ranging from mild to severe forms. Severe neurological symptoms were also found in patients despite minimal dermal involvement.

Air pollution and upper respiratory symptoms in children from East Germany.

Whereas evidence of adverse effects of air pollution on lower respiratory tract illnesses in children is increasing, little is known about the effects of high and moderate levels of air pollution on the incidence of upper respiratory illnesses. 9 to 11 year old schoolchildren (n = 1,854) living in Leipzig, East Germany were studied. The presence of upper respiratory symptoms was documented by a physician. Daily mean and maximum concentrations of SO2, particulate matter (PM) and NOx, as well as temperature and humidity, were measured. Furthermore, a self-administered questionnaire was distributed to the parents to assess confounding factors. Parents of 1,500 (81%) children returned the questionnaire. When controlling for paternal education, passive smoke exposure, number of siblings, temperature and humidity, increased risks for the development of upper respiratory symptoms were found in the winter months for SO2 mean concentrations (odds ratio (OR) = 1.72; 95% confidence interval (95% CI) 1.19-2.49). NOx mean concentrations (OR = 1.53; 95% CI 1.01-2.31) and PM maximum values (OR = 1.62; 95% CI 1.08-2.45). In the summer months, only NOx mean concentrations were associated with a significantly increased risk (OR = 1.82; 95% CI 1.21-2.73). A combination of high mean levels of different pollutants resulted in the highest risk (OR = 2.10; 95% CI 1.30-3.37 in the winter, and OR = 2.16; 95% CI 1.23-3.81 in the summer). We conclude that high concentrations of SO2, and moderate levels of particulate matters and NOx are associated with an increased risk of developing upper respiratory symptoms in childhood.(ABSTRACT TRUNCATED AT 250 WORDS)

Pertussis infection and allergic sensitization.

BACKGROUND: The immunogenic activity of B. pertussis infection has been described in various laboratory, animal, and clinical studies. There is, however, no information on the impact of pertussis on allergies in the total population. OBJECTIVE: To compare the prevalence of allergic sensitization and allergic rhinitis in children with and without previous pertussis infection. METHODS: A population-based, cross-sectional study was carried out on 13,937 10-year-old children in the western (Munich and Southern Bavaria) and eastern parts of Germany (Leipzig and the region around Halle). A total of 11,969 questionnaires (85.9%) given to the parents were collected. Data from 9,484 German children (questionnaire and skin prick tests with six different allergens) were analyzed. RESULTS: Pertussis was much more common in the western than in the eastern part of Germany. The adjusted odds ratio for any allergic sensitization after pertussis was only slightly increased in western Germany with 1.3 (95% confidence limits 1.2 to 1.5) and in eastern Germany with 1.5, (1.2 to 1.8) but not for allergic rhinitis with 1.0 (0.7 to 1.4) and in Eastern Germany 1.3 (0.8 to 1.9). CONCLUSIONS: Infection with pertussis seems to have only a weak influence on allergic sensitization and does not explain the observed differences in allergic sensitization between western and eastern Germany.

Bronchial hyperreactivity and history of wheezing in children.

UNLABELLED: The objective of this analysis was to determine the relationship between wheezing at different age groups in children and the prevalence of bronchial hyperreactivity at the age of 10. A population-based cross-sectional study was conducted in Leipzig and the region around Halle in Germany. Of 3105 10-year-old children, 2658 questionnaires (85.6%) were returned. In addition 2279 (73.4%) pulmonary function tests were performed before and after cold air challenge. 658 children (24.8%) had recurrent wheezing during their lifetime. In 579 children the individual time course could be evaluated (46 children with and 533 without a physician-confirmed diagnosis of asthma). Wheezing began most frequently in the 1st year of life (44.1% of all wheezing children) with the highest annual prevalence in the 3rd year (71.0% of all wheezing children). Wheezing which started in the first 2 years of life, had disappeared in most of the children by the age of 10. However, if wheezing began later than the 3rd year it was more persisting. Bronchial hyperreactivity measured after cold air challenge was higher in the group with recurrent wheezing (24.1%) than in the group without wheezing (18.8%, P = 0.004). CONCLUSION: Wheezing is a very common symptom in childhood and only partly associated with later bronchial hyperreactivity. On the other hand, asthma is often not diagnosed despite bronchial hyperreactivity and many years of wheezing.

Skin test reactivity and number of siblings.

OBJECTIVE: To investigate the relation between skin test reactivity in children and number of siblings. DESIGN: Cross sectional survey among schoolchildren aged 9-11 years. Skin prick tests in the children and self completion of written questionnaire by their parents. SUBJECTS: 5030 children in Munich and 2623 children in Leipzig and Halle, Germany. MAIN OUTCOME MEASURES: Atopic status assessed by skin prick tests. RESULTS: After possible confounders were controlled for, the prevalence of atopic sensitisation decreased linearly with increasing number of siblings (odds ratio = 0.96 for one sibling, 0.67 for five or more siblings; P = 0.005). In atopic children the severity of the skin test reaction as assessed by the weal size was not associated with the number of siblings. CONCLUSIONS: Factors directly or indirectly related to the number of siblings may decrease the susceptibility of children to become atopic. Thus, declining family size may in part contribute to the increased prevalence of atopic diseases reported in Western countries over the past few decades.

Prevalence of asthma and atopy in two areas of West and East Germany.

The German reunification offers a unique opportunity to study the impact of environmental factors on the development of childhood respiratory and allergic disorders in ethnically similar populations. We investigated the prevalence of asthma, hay fever, atopy, and bronchial hyperresponsiveness (BHR) in 9- to 11-year old children in West Germany (n = 5,030) and East Germany (n = 2,623). A self-administered questionnaire was distributed to the parents. Children underwent cold air challenge and allergy skin prick tests. Atopic sensitization was considerably more frequent in West German children than in their peers in East Germany (36.7% versus 18.2%; odds ratio [OR] = 2.6, p < 0.0001). The prevalence of current asthma and hay fever was significantly higher in West Germany when compared with that in East Germany (5.9% versus 3.9%; OR = 1.5, p < 0.0001 and 8.6% versus 2.7%; OR = 3.4, p < 0.0001, respectively). Bronchitis, however, was more prevalent in East Germany than in the western part of the country. The prevalence of BHR as assessed by cold air challenge was higher in West Germany compared with that in East Germany (8.3% versus 5.5%, OR = 1.6, p < 0.001). Logistic regression showed that the West German study area was no longer a significant independent determinant of asthma once sensitization to mites, cats, and pollen was taken into account. We conclude that sensitization to aeroallergens is strikingly more frequent in West Germany than in East Germany and this may explain the differences in the prevalence of asthma and hay fever between the two parts of the country.

[The language of pediatric asthma patients. A study of symptom description]. / Die Sprache asthmakranker Kinder. Eine Untersuchung zur Symptombeschreibung.

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.

Prevalence of asthma and allergic disorders among children in united Germany: a descriptive comparison.

OBJECTIVES: To compare the prevalence of asthma and allergic disorders among children in Munich, western Germany, and Leipzig, eastern Germany, where environmental exposure, particularly air concentrations of sulphur dioxide and particulate matter, and living conditions have differed over the past 45 years. DESIGN: Prevalence surveys among school-children aged 9-11 years in Leipzig and Munich. Self completion of written questionnaire by the children's parents and lung function measurements. SUBJECTS: 1051 children in Leipzig and 5030 in Munich. SETTING: Primary schools. MAIN OUTCOME MEASURES: Reported lifetime prevalence of asthma and allergic disorders, and bronchial hyperresponsiveness assessed by cold air inhalation challenge. RESULTS: The lifetime prevalence of asthma diagnosed by a doctor was 7.3% (72) in Leipzig and 9.3% (435) in Munich; prevalence of wheezing were 20% (191) and 17% (786) respectively. The prevalence of diagnosed bronchitis was higher in Leipzig than Munich (30.9% (303) v 15.9% (739); p < 0.01). A significant drop in forced expiratory volume (> 9%) after cold air challenge was measured in 6.4% (57) of children in Leipzig and in 7.7% (345) of those in Munich. Hay fever (2.4% (24) v 8.6% (410); p < 0.01) and typical symptoms of rhinitis (16.6% (171) v 19.7% (961); p < 0.05) were reported less often in Leipzig than in Munich. CONCLUSIONS: No significant differences were seen in the lifetime prevalence of asthma, wheezing, and bronchial hyperresponsiveness between children in Leipzig and Munich. The lifetime prevalence of bronchitis was higher in Leipzig than in Munich. The lower prevalence rates of allergic disorders in Leipzig could point toward aetiological factors that are associated with Western lifestyle and living conditions.

[A skin button to anchor and lead out catheters or cable links from the skin]. / Hautknopf zur Verankerung und Herausführung von Kathetern oder Kabelverbindungen aus der Haut.

The manufacture of a skin button for use in chronic animal experiments is described, which is made of silicone rubber and intended to anchor the exit site of intravascular catheters. The button holds the catheter permanently in the skin and can also be used to anchor connections for occlusion cuffs and cables leading to implanted measuring elements.

[Improved estimation of parameters of blood pressure regulation in anesthetized dogs]. / Verbesserte Systemparameterschätzung der Blutdruckregulation bei anästhesierten Hunden.

Estimation of parameters was based on tilting table tests in anaesthetized mongrel dogs. The registered variables were the carotid sinus pressure, aortic and superior vena cava pressure as well as the e.c.g. An orthostatic loading series after experimental designs of first order of Plackett and Burman served as an additional disturbance, which is necessary for a model in a closed loop system. Systemic parameters were estimated from measured data by means of recursive regression and generalized recursive regression. A discrepancy between the excellent animal tests and the quality of the model of subsequent estimation of parameters suggested a filtration of measured data, and a non-linear model (Hammerstein model) was selected for comparison. Contrary to the Hammerstein model, filtration of data led to a considerable improvement of the estimated parameters in the present study.

[Simple dynamic model of the human blood pressure regulatory system as based on the orthostatic load sequence]. / Dynamisches Grobmodell des Blutdruckregelkreises vom Menschen auf der Grundlage orthostatischer Belastungsfolgen

The two statistical parameter estimation methods, the recursive least squares and the recursive generalized least squares, are dealt with briefly. An additional noncorrelated disturbance is necessary for unbiased parameter estimation in the closed-loop system. The disturbance is realized by an orthostatic load sequence shaped according to the experimental programme. Men and women were subjected to head-up tilt between 10 degrees and 55 degrees. The disturbance, mean blood pressure and heart rate were measured. These discrete data were used for parameter estimation of transfer functions.