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P Reitmeir

Publications and source records attributed to P Reitmeir.

At least 19 recordsLinked to original sources

Resampling-based methods for the analysis of multiple endpoints in clinical trials.

We consider multivariate tests for comparing two treatments with multiple endpoints. The test decision is drawn from the simultaneous consideration of the univariate tests for the single endpoints. A general class of these tests, called cut-off tests, can be given, which, however, can lead to highly conservative procedures because the dependencies among the endpoints are not taken into account. In applying resampling-based methods considerable improvements for these tests can be achieved. Resampling-based cut-off tests are proposed which are sensitive against a treatment difference in a single endpoint, in a subgroup of endpoints, or in all endpoints. The results of Monte Carlo simulations demonstrate that a remarkable gain in statistical power as compared to the crude simultaneous consideration can be reached. In particular, for the multivariate one-sided test situation the proposed tests can be recommended. As an example the application of the tests is demonstrated by data from a clinical trial.

Clinical Trials as Topic↗

Health effects of sulfur-related environmental air pollution. I. Executive summary.

The motivation of simulating real-world environmental exposure in a number of long-term studies with dogs was to address the question of whether or not perpetual inhalation of air pollutants can initiate diseases in healthy lungs and can thus contribute to the increasing prevalence of respiratory diseases in industrialized countries. The major conclusion of this article is that this question has to be answered in the negative for the simultaneous inhalation of the major constituents of combustion-related air pollution, particle-associated sulfur(IV), and particle-associated hydrogen ions. Over 13 mo, 8 healthy beagle dogs were exposed in 2 whole-body chambers daily for 16.5 h to 1 microm neutral sulfite [sulfur(IV)] particles at a mass concentration of 1.5 mg m-3 and for 6 h to 1.1 microm acidic sulfate particles carrying 15 micromol m-3 hydrogen ions into the canine lungs. This longitudinal study was characterized by repeated observations of individual respiratory response patterns. To establish baseline data the dogs were repeatedly examined preexposure while the chambers were ventilated over 16 mo with clean air. Each individual served thus as its own control. Another eight dogs served as additional controls. They were housed in 2 chambers ventilated with clean air over the entire study period of 29 mo. To assess response patterns, respiratory lung function tests were performed pre- and postexposure, segmental lung lavages were repeatedly performed to obtain epithelial lining fluid from the lungs for analysis of cell content, cell function, and biochemical indicators of lung injury, and radiolabeled test particles were used to study pathways of intrapulmonary particle elimination. At the end of the study, the lungs of all animals were morphologically and morphometrically examined. Functional and structural responses were finally compared to those observed previously as a result of a sole exposure of canine lungs to neutral sulfite particles over 10 mo (Heyder et al., 1992). Interactions between responses induced by neutral sulfite and acidic sulfate particles occurred, but antagonism rather than synergism was observed. The responses induced by sulfur(IV) were less pronounced, not detectable, or even reversed when hydrogen ions were also delivered to the lungs. On the other hand, responses not induced by the sole exposure to sulfur(IV) were observed: The activity of alkaline phosphatase was elevated and type II pneumocytes proliferated. It can, however, be concluded that long-term exposure of healthy lungs to particle-associated neutral sulfur(IV) and hydrogen ions at concentration close to ambient levels causes subtle respiratory responses but does not initiate pathological processes in the lungs. In other words, the perpetual inhalation of sulfur(IV) and hydrogen ions from the atmospheric environment presents no health risk to the healthy lungs. It is thus also very unlikely that respiratory diseases can be initiated by the inhalation of these pollutants.

Air Pollutants, Occupational↗

Health effects of sulfur-related environmental air pollution. II. Cellular and molecular parameters of injury.

Recently, concern has been raised about effects related to environmental sulfur and/or acidic aerosols. To assess long-term effects on nonrespiratory lung function, 8 beagle dogs were exposed over a period of 13 mo for 16.5 h/day to a neutral sulfite aerosol at a sulfur(IV) concentration of 0.32 mg m(-3) and for 6 h/day to an acidic sulfate aerosol providing a hydrogen concentration of 15.2 micromol m(-3) for inhalation. Prior to exposure the dogs were kept under clean air conditions for 16 mo to establish physiological baseline values for each animal. A second group of eight dogs (control) was kept for the entire study under clean air conditions. No clinical symptoms were identified that could be related to the combined exposure. Biochemical and cellular parameters were analyzed in sequential bronchoalveolar lavage (BAL) fluids. The permeability of the alveolo-capillary membrane and diethylenetriaminepentaacetic acid (DTPA) clearance was not affected. Similarly, oxidant burden of the epithelial lining fluid evaluated by levels of oxidation products in the BAL fluid protein fraction remained unchanged. Both the lysosomal enzyme beta-N-acetylglucosaminidase and the alpha-1-AT were increased (p <.05). In contrast, the cytoplasmic marker lactate dehydrogenase remained unchanged, indicating the absence of severe damages to epithelial cells or phagocytes. Various surfactant functions were not altered during exposure. Three animals showed elevated levels of the type II cell-associated alkaline phosphatase (AP), indicating a nonuniform response of type II cells. Significant correlations were found between AP and total BAL protein, but not between AP and lactate dehydrogenase, suggesting proliferation of alveolar type II cells. Absolute and relative cell counts in the BAL fluid were not influenced by exposure. Alveolar macrophages showed no alterations with regard to their respiratory burst upon stimulation with opsonized zymosan. The percentage of alveolar macrophages capable of phagocytozing latex particles was significantly decreased (p<.05), while the phagocytosis index was not altered. In view of the results of this and previous studies, we conclude that there is no synergism of effects of these two air pollutants on nonrespiratory lung functions. It is hypothesized that antagonistic effects of these air pollutants on phospholipase A2-dependent pathways account for compensatory physiological mechanisms. The results emphasize the complexity of health effects on lung functions in response to the complex mixture of air pollutants and disclose the precariousness in the risk assessment of air pollutants for humans.

Aerosols↗

Health effects of sulfur-related environmental air pollution. III. Nonspecific respiratory defense capacities.

Recently concern has been raised about health effects related to environmental sulfur and/or acidic aerosols. To assess long-term effects on respiratory lung function, 8 beagle dogs were exposed over a period of 13 mo for 16.5 h/day to 1.0 microm neutral sulfite aerosol with a particle associated sulfur(IV) concentration of 0.32 mg m(-3) and for 6 h/day to 1.1 microm acidic sulfate aerosol providing an hydrogen ion concentration of 15.2 micromol m(-3) for inhalation. Prior to exposure the dogs were kept under clean air conditions for 16 mo to establish physiological baseline values for each dog. A second group of eight dogs (control) was kept for the entire study under clean air conditions. Nonspecific defense mechanisms in the airways and in the peripheral lung were studied during chronic exposure of the combination of neutral sulfur(IV) and acidic sulfur(VI) aerosols. No functional changes of tracheal mucus velocity were found, in agreement with unchanged morphometry of the airways. However, the exposure resulted in changes of several alveolar macrophage (AM) mediated particle clearance mechanisms: (1) Based on in vivo clearance analysis and cultured AM studies using moderately soluble cobalt oxide particles, intracellular particle dissolution was significantly reduced since phagolysosomal proton concentration was decreased. We deduce exposure-related malfunction of proton pumps bound to the phagolysosomal membrane as a result of an increase of cytosolic proton concentration. (2) Based on in vivo clearance analysis using insoluble polystyrene particles, AM-mediated particle transport from the lung periphery toward ciliated terminal bronchioli and further to the larynx was significantly reduced. Activation of epithelial type II cells at the entrance of alveoli was inferred from observed type II cell proliferation at those alveolar ridges and enhanced secretion of alkaline phosphatase in the fluid of bronchoalveolar lavages. As a result, hypersecretion of chemotactic mediators by activated type II cells at these loci led to the observed decrease of particle transport toward ciliated bronchioli. (3) Based on in vivo clearance analysis using insoluble polystyrene particles, particle transport from the alveolar epithelium into interstitial tissues was increased and (4) particle transport to the tracheobronchial lymph nodes was significantly enhanced. Particle transport into interstitial tissues is the most prominent clearance pathway from the canine alveolar epithelium. We conclude that the deteriorated particle transport toward ciliated terminal bronchioli resulted in an enhanced particle transport across the epithelial membrane into interstitial tissues and the lymphatic drainage. The observed alterations in alveolar macrophage-mediated clearance mechanisms during chronic exposure of these air pollutants indicate an increased risk of health.

Aerosols↗

Renal function and renotropic effects of secretin in cystic fibrosis.

In ten cystic fibrosis patients and nine age-matched controls, renal function was determined before and after infusion of secretin. Under baseline conditions creatinine excretion and clearance were significantly elevated, exclusively due to those patients who were homozygous for the DF508 mutation (153 vs 132 ml/min*1.73m2), whereas the glomerular filtration rate, measured by inulin clearance showed no difference. Renal plasma flow and the fractional reabsorption rates of electrolytes were similar in patients and controls. During secretin infusion renal plasma flow increased and the fractional reabsorption rates of electrolytes decreased in both groups. The patients had a increased metabolic clearance (2900 vs 1660 ml/min*m2) and endogenous production rate (9,9 vs 2,5 pmol/min*m2) of of secretin. In conclusion global renal function and electrolyte handling, in particular chloride permeability, are unchanged in cystic fibrosis. Individuals expressing the DF508 genotype showed a selective elevation of creatinine excretion and clearance. The secretion and metabolic clearance of secretin are increased in cystic fibrosis.

Adolescent↗

The association between baseline lung function and bronchial responsiveness to methacholine.

It has been reported that females show an increased frequency of bronchial hyperresponsiveness (BHR) compared to males and that this difference is abolished after taking into account differences in baseline FEV1. The aim of our study was to analyse how the distribution of BHR in males and females depends on the definition of BHR. Special emphasis was paid to the question whether the prevalence rates of BHR according to different definitions were related to baseline characteristics of the subjects and baseline lung function in the same manner. We analysed the data obtained within the European Community Respiratory Health Survey (ECRHS) in the Eastern German population sample of Erfurt aged 20-65 years (n = 931). In logistic regression analyses of different definitions of BHR, we used as parameters age, height, gender, smoking habits, baseline forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1 as a percent of FVC (FEV1% FVC). Symptoms and reported diagnosis of asthma did not significantly depend on gender or age. When BHR was defined as the provocative dose causing a 20% fall in FEV1, BHR was more prevalent in females than in males (27.6% vs. 13.2%). Similar gender differences were found when defining BHR via a 10% fall in FEV1 or by using corresponding cut-off values of the linear dose-response slopes of the percent decline in FEV1 (DRS). Multiple linear regression analyses of various transformations of the DRS also indicated a higher degree of BHR in females. Independently of the definition chosen, however, the gender difference in the prevalence of BHR disappeared when height and FEV1 or FEV1% FVC or appropriate combinations were included in the model. The reciprocally transformed DRS showed the best resolution of the spectrum of bronchial responsiveness. These data are compatible with the hypotheses that (1) estimates of the distribution of BHR are distorted by differences in the methacholine dosage per lung size and that (2) airway geometry affects the measurement of BHR. It appears that these factors and not intrinsic differences in BHR between males and females contribute to the gender differences in the prevalence of BHR. Furthermore, our data support the superiority of the dose response slope for the analysis of bronchial responsiveness in epidemiologic surveys.

Adult↗

Correlation of developmental neurological findings with spectral analytical EEG evaluations in pre-school age children.

For the differentiation of developmental neurological disorders in pre-school age children, the relationship between automatically derived EEG parameters and developmental neurological findings was investigated. Within the scope of the Munich Pediatric Longitudinal Study, the sample sets of 4- and 5-year-old children (according to the frontal and parieto-occipital EEG derivations) with selected abnormal findings categorized by special items were compared with the corresponding control groups. This was carried out by means of one-sided t tests and relative frequency band-related as well as single-step spectral power parameters in the alpha range of the EEG. Automatic analysis using single-step power values was superior to that using band-related parameters. This led to the conclusion that use of age-specific single-step parameters for a quantitative EEG analysis and ignoring the classical frequency bands will yield statistically greatly improved results. For 4- and 5-year-old children, the best separation of the neurologically abnormal groups from the normal control groups was obtained using relative spectral values in the frequency range of 9.0-9.8 Hz with a maximum at 9.4 Hz. At the same time, the topographical conditions of brain immaturation should be taken into account. The results for the children examined in this study differ in a stronger distinction over the frontocentral brain region of 4- and 5-year-olds (P < 0.01) and through an additional distinction over the parietooccipital region of the 5-year-olds (P < 0.001). It still must be tested whether the spectral parameter at 9.4 Hz is age-specific for 4- and 5-year-old children or whether in other age groups different spectral parameters are of use. As an examiner-independent method, the automatic EEG analysis should become an integral component of developmental neurological diagnostics.

Attention Deficit Disorder with Hyperactivity↗

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.

Asthma↗

Severity of childhood asthma by socioeconomic status.

BACKGROUND: A review of studies on the association between childhood asthma and socioeconomic status (SES) in industrialized countries leads to the conclusion that there does not seem to be a clear association. A study from Aberdeen published 25 years ago, however, shows that among children with asthma, severe asthma is most prevalent in the lower social class, but this distinction between grades of asthma severity has been largely ignored since. METHODS: We screened all fourth grade schoolchildren of German nationality in Munich (4434 children, response rate 87 percent), distinguishing three severity grades in the same way as the study in Aberdeen. RESULTS: Prevalences of childhood asthma are reported by severity grade and SES. Prevalence of severe asthma was found to be significantly higher in the low as compared with the high socioeconomic group (Odds ratio = 2.37; 95 percent confidence interval: 1.28-4.41). This association could not be explained by established risk factors. CONCLUSIONS: More attention should be paid to the association between severe asthma and SES, with measures such as targeting early diagnosis and treatment towards low socioeconomic groups.

Asthma↗

Dose response for heritable translocations induced by acrylamide in spermatids of mice.

A heritable translocation test was carried out with acrylamide (AA) to obtain a dose-response relationship for induction of reciprocal translocations in late spermatids of the mouse. Male C3H/E1 mice were treated with single i.p. doses of 50 and 100 mg/kg of acrylamide and mated 7-16 days after treatment to untreated female 102/E1 mice. Translocation carriers among the F1 progeny were selected by a sequential procedure of fertility testing and cytogenetic analysis including G-band karyotyping to determine the chromosomes involved in the respective translocations. The translocation frequencies observed with 50 mg/kg and 100 mg/kg of AA were 0.6% and 2.7%, respectively. The historical control translocation frequency was 0.04%. Doubling dose estimates based on these and previous data are discussed.

Acrylamide↗

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.

Child↗

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.

Age Factors↗

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.

Asthma↗

Road traffic and adverse effects on respiratory health in children.

OBJECTIVES: To examine whether road traffic in a big city has a direct effect on pulmonary function and respiratory symptoms in children. DESIGN: Cross sectional study. SETTING: Of all 7445 fourth grade children (aged 9-11 years) in Munich, 6537 were examined. Of the children with German nationality and the same residence during the past five years and known exposure data, 4678 questionnaires and 4320 pulmonary function tests could be analysed. MAIN OUTCOME MEASURES: Variables of pulmonary function by forced expiration and respiratory symptoms reported in a questionnaire; census data on car traffic collected in the school district. RESULTS: Density of car traffic ranged from 7000 to 125,000 cars per 24 hours. Multiple regression analysis of peak expiratory flow showed a significant decrease of 0.71% (95% confidence interval 1.08% to 0.33%) per increase of 25,000 cars daily passing through the school district on the main road. Maximum expiratory flow when 25% vital capacity had been expired was decreased by 0.68% (1.11% to 0.25%). In contrast, response to cold air challenge was not increased. The adjusted odds ratio for the cumulative prevalence of recurrent wheezing with the same exposure was 1.08 (1.01 to 1.16). Cumulative prevalence of recurrent dyspnoea was increased, with an odds ratio of 1.10 (1.00 to 1.20). Lifetime prevalence of asthma (odds ratio 1.04; 0.89 to 1.21) and recurrent bronchitis (1.05; 0.98 to 1.12) were not significantly increased. CONCLUSIONS: High rates of road traffic diminish forced expiratory flow and increase respiratory symptoms in children.

Automobiles↗

Evaluation of cold air challenge data in a population sample using a model of bronchial hyperreactivity and disposition to bronchial obstruction.

To explore the role of bronchial hyperreactivity and obstruction after cold air challenge, data from a cross-sectional study of more than 7,000 10-year-old children were used. Current knowledge of hyperreactivity is primarily based on pharmacological provocation tests with variable prechallenge flow rates and their decrease relative to baseline. Using forced expiratory volume (FEV) in 1 sec values before and after cold air challenge, however, it is possible to define a subsample of children with predominant hyperreactivity and a subsample with predominant obstruction after challenge. The prevalence of respiratory symptoms and the diagnoses in the two subsamples were compared. The analysis showed that children with bronchial obstruction have nearly the same frequency of respiratory symptoms as those with bronchial hyperreactivity. A combined model of bronchial obstruction and hyperreactivity was, therefore, more predictive of symptoms than a model of hyperreactivity alone.

Air↗

Reactivity to cold-air hyperventilation in normal and in asthmatic children in a survey of 5,697 schoolchildren in southern Bavaria.

The measurement of bronchial hyperreactivity (BHR) may give additional information to questionnaire-based studies of asthma prevalence. It is desirable to have a provocation method with high specificity that avoids the use of pharmacologic provocations in large numbers of healthy children. It was the aim of this study to establish a range of values for responsiveness to cold-air challenge in normal children, to describe its specificity and sensitivity for a diagnosis of asthma in a large unselected sample of schoolchildren in a field study, and to measure factors associated with hyperresponsiveness. All fourth-grade schoolchildren (9 to 11 yr of age) in Munich and several southern Bavarian communities (n = 9,403) were surveyed with a questionnaire (response rate, 87%), baseline lung function, and cold-air hyperventilation challenge (n = 5,697). A diagnosis of asthma was reported in 7.9% of children. In the reference group, the ninety-fifth percentile (%ile) for the change of FEV1 (DFEV1) was -9.0%; the 90%ile was -7.3%. Asymptomatic children fulfilling all criteria for the reference group showed a significantly increased reactivity if they had a family history of asthma (p = 0.038). With a cutoff for DFEV1 of -9.0% or -7.3% the respective sensitivities to "detect" a diagnosis of asthma were 21.6 and 30.7%, and for asthma with symptoms during the previous 12 months it was 26.2 and 35.1%. Reactivity to cold air increased with the number of episodes of asthma in the previous 12 months. In a multiple linear regression model, factors associated with increased reactivity to cold air were diagnosed asthma, hay fever, male sex, younger age, and a positive skin test.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗