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Biomedical subjects

R Bergmann

Publications and source records attributed to R Bergmann.

At least 55 records · Page 3Linked to original sources

Assessment of long-term bronchiolar clearance of particles from measurements of lung retention and theoretical estimates of regional deposition.

Twelve healthy nonsmokers inhaled monodisperse Teflon particles labelled with 51Cr (half-life 27.8 days) with an aerodynamic diameter (dae) of 6.1 microns, 5 at a normal flow, 0.5 L/s, and 7 at an extremely slow flow, 0.05 L/s. Lung retention after 24 hours was measured for about 6 months and could be well described by a 2-component exponential function. After the normal inhalation, 14% of the particles retained after 24 hours cleared with a half-time of 3.7 days and 86% with a half-time of 217 days. After the slow inhalation, 35% of the particles retained after 24 hours cleared with a half-time of 3.6 days and 65% with a half-time of 170 days. Deposition was calculated using 3 different models including the recent Human Respiratory Tract Model (HRTM), adopted by the International Commission on Radiological Protection (ICRP), and a model based on Monte Carlo particle transport, together with an asymmetric lung model. Generally, the 3 models agreed fairly well and predicted a considerably higher deposition in the bronchiolar region (generations 9-15) at the slow flow than at the normal flow. Together, the experimental data and the predictions of the deposition models indicate that about 40% of the particles deposited in the conducting airways during the slow inhalation were retained after 24 hours. They also strongly indicate that the particles which cleared with a half-time of about 4 days were mainly deposited in the bronchiolar region, and that about 25% of the particles deposited in the bronchiolar region cleared in this phase. The experimental data agreed quite well with the HRTM predictions made using its default parameter values for slow clearance in the bronchial tree.

Administration, Inhalation↗

Simultaneous measurement of [18F]FDOPA metabolism and cerebral blood flow in newborn piglets.

Available information on the dopamine (DA) metabolism of the immature brain is rare. In order to establish a useful animal model we have performed PET experiments in anesthetized neonatal pigs using 6-[18F]-fluoro-L-DOPA (FDOPA) as tracer. In this study, we have simultaneously determined the cerebral blood flow and the rate constant of FDOPA conversion by the aromatic amino acid decarboxylase, the ultimate enzyme in the synthesis of dopamine. The estimated values of FDOPA decarboxylation in the basal ganglia were similar to values calculated in adult animals and humans. However, in contrast to those studies a significant decarboxylation was also found in the frontal cortex and the cerebellum. HPLC analysis of brain samples also revealed extensive and rapid metabolism of FDOPA in the five investigated brain regions. At 8 min after tracer injection about 80% of FDOPA was already converted to FDA and its metabolites. Surprisingly, a rather high fraction (16-21%) of [18F]-fluoro-3-methoxytyramine was found which may indicate a low storage capacity of vesicular DA at this perinatal stage. It is suggested that the findings are related to the ontogenetic development of the dopaminergic system. The knowledge of the regulation of the DA metabolism in the immature brain may have implications for the understanding of neurodevelopmental effects of perinatal oxygen deprivation.

Animals↗

Case-based reasoning for medical decision support tasks: the Inreca approach.

We describe an approach for developing knowledge-based medical decision support systems based on the new technology of case-based reasoning. This work is based on the results of the Inreca European project and preliminary results from the Inreca + project which mainly deals with medical applications. One goal was to start from case-based reasoning technology for technical diagnosis and 'scale-up' to more general non-technical decision support tasks as typically given in medical domains. Inreca technology has been used to build an initial decision support system at the Russian Toxicology Information and Advisory Center in Moscow for diagnosing poison cases caused by psychotropes.

Artificial Intelligence↗

Prediction of sensitization to inhalant allergens in childhood: evaluating family history, atopic dermatitis and sensitization to food allergens. The MAS Study Group. Multicentre Allergy Study.

BACKGROUND: A family history of atopy is a poor predictor of sensitization to inhalant allergens and allergic disease during childhood. We recently identified early sensitization to food allergens, especially hen's egg, as a valuable predictor of subsequent sensitization to inhalant allergens. OBJECTIVE: (1) Whether prediction will be improved by in vitro allergy tests at 1 year of age in combination with family history and medical history data. (2) Comparison with the capacities of in vitro tests to predict sensitization to aeroallergens. METHODS: Of an observational birth cohort study (MAS) 49 children who were sensitized to inhalant allergens at 5 years of age and 116 non-sensitized controls were included in the present study. For the prediction of sensitization to inhalant allergens the following prognostic factors were evaluated: atopic family history (FH), atopic dermatitis (AD) during the first year of life, two in vitro allergy tests for specific IgE to common food allergens at 1 year of age (fx5 [Pharmacia] and single allergen specific tests (sIgE) for four allergens) and 'high' total serum IgE, defined by three different cut off points. RESULTS: The combination of medical history data and laboratory tests resulted in the best predictive discrimination. The positive predictive values (PPV) were higher if sensitization to food was detected by single allergen specific tests (PPV: 66%/75%/100% corresponding to the three evaluated risk groups) than by the qualitative fx5 (PPV: 46%/65%/100%). The negative predictive values were equal for both tests (69 and 92% for the two low risk groups). High total serum IgE had low predictive capacity. CONCLUSION: During infancy the prediction of sensitization to inhalant allergens should be based on medical history data and allergy tests determining sensitization to food allergens. The in vitro tests improve the predictive discrimination, but the individual risk profile of the child must be considered for a reliable and valid prediction.

Allergens↗

Mrp1 multidrug resistance-associated protein and P-glycoprotein expression in rat brain microvessel endothelial cells.

Two membrane glycoproteins acting as energy-dependent efflux pumps, mdr-encoded P-glycoprotein (P-gp) and the more recently described multidrug resistance-associated protein (MRP), are known to confer cellular resistance to many cytotoxic hydrophobic drugs. In the brain, P-gp has been shown to be expressed specifically in the capillary endothelial cells forming the blood-brain barrier, but localization of MRP has not been well characterized yet. Using RT-PCR and immunoblot analysis, we have compared the expression of P-gp and Mrp1 in homogenates, isolated capillaries, primary cultured endothelial cells, and RBE4 immortalized endothelial cells from rat brain. Whereas the mdr1a P-gp-encoding mRNA was specifically detected in brain microvessels and mdr1b mRNA in brain parenchyma, mrp1 mRNA was present both in microvessels and in parenchyma. However, Mrp1 was weakly expressed in microvessels. Mrp1 expression was higher in brain parenchyma, as well as in primary cultured brain endothelial cells and in immortalized RBE4 cells. This Mrp1 overexpression in cultured brain endothelial cells was less pronounced when the cells were cocultured with astrocytes. A low Mrp activity could be demonstrated in the endothelial cell primary monocultures, because the intracellular [3H]vincristine accumulation was increased by several MRP modulators. No Mrp activity was found in the cocultures or in the RBE4 cells. We suggest that in rat brain, Mrp1, unlike P-gp, is not predominantly expressed in the blood-brain barrier endothelial cells and that Mrp1 and the mdr1b P-gp isoform may be present in other cerebral cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Development of latex allergy in children up to 5 years of age--a retrospective analysis of risk factors.

The aim of the study was to investigate possible associations between the time course of early sensitization to latex and various life style factors. Of the 398 children from a prospective birth cohort study, 20 (5%) showed specific serum IgE to latex at the age of 5 years. Sensitization started beyond the first year of life and 19 out of 20 sensitized children showed increasing specific IgE-values over time. All 20 sensitized children were atopic (p < 0.00000). Total IgE was significantly higher in the sensitized group (median 394.5 kU/I) than in the non-sensitized group (median 39.2 kU/l) (p < 0.00001). Comparing the latex-sensitized group with the non-sensitized children, there were significantly more operations in the latex group (p < 0.05) during the first 5 years of life. Medical history, certain foods, the use of pacifiers, mattress composition and socio-economic data proved not to be significant risk factors. From our study we conclude that besides the number of operations and an atopic predisposition--no other definite risk factor for developing sensitization or allergy to latex (such as everyday household objects) can be identified in children up to 5 years of age.

Age Factors↗

Long-lasting sensitization to food during the first two years precedes allergic airway disease. The MAS Study Group, Germany.

The purpose of the study was to investigate whether the duration of sensitization to food allergens during early childhood is related to later development of IgE mediated hypersensitivity to inhalant allergens and of allergic rhinitis and asthma in 5-year-old children and whether long-lasting food-sensitization may be used to predict subsequent allergic airway diseases. Five hundred and eight children of a prospective birth cohort study with available serum samples at one and two years of age were included and followed up until five years of age. Specific sensitization to food and inhalant allergens and the occurrence of subsequent allergic airway diseases were determined. Children with a long-lasting sensitization to food allergens (persistently sensitized for more than one year) produced significantly higher total IgE and specific IgE levels than children who were only transiently food-sensitized by two years of age. Children persistently sensitized to food had a 3.4 fold higher risk of developing allergic rhinitis and a 5.5 fold higher risk of developing asthma than infants who were only transiently food sensitized. Persistent food sensitization in combination with a positive atopic family history was a strong predictor for the development of allergic rhinitis and asthma at five years of age. The risks for these children are up to 50%, and 67% respectively. Persistently detectable sensitization to food over more than one year in early childhood is a strong prognostic factor for subsequent allergic airway disease. Persistently food-sensitized children especially in atopic families have to be regarded as a high-risk group and should be considered for preventive measures against respiratory atopy.

Administration, Inhalation↗

Refinement of blood sampling from the sublingual vein of rats.

A refined method of repeated blood sampling is described: the tongue of the anaesthetized rat is pulled forward with the fingers and the sublingual vein is punctured with a 23 gauge hypodermic needle. Based on the requirement of a pharmacokinetic study, 0.5 or 1 ml of blood was collected 7 times at 0, 0.5, 1, 2, 4, 8 and 24 h. The degree of suffering was judged by determining the body weight and food and water consumption. All animals showed an increase in body weight already after 24 h and, therefore, the method of collecting blood from the sublingual vein can be recommended for repeated blood sampling. The haematological evaluation of groups of animals with differing body weight showed that sample volumes of up to 15% of the total blood volume lead to haematocrit values of approximately 40%. A remarkable initial drop in white blood cell counts followed by a marked rise 2 h after first sampling to values partly above the pre-test could not be directly related to the extracted blood volume.

Anesthesia↗

Whole population or high-risk group? Childhood asthma.

Allergen avoidance seems to be a logical way to protect high-risk children from the development of allergic diseases. If we assume that allergic diseases are predictable, we firstly need to define which allergic disease and what age we are discussing. Then the predictive capacity of risk factors, their clinical value and their prevalence in the population has to be considered. In newborns, the positive predictive value of family history and an elevated cord blood immunoglobulin E for atopic disorders in the first 2 yrs of life was well under 50% in high-risk cohorts. In the multicentre allergy study (MAS)-90 in Germany, 40% of children 3-5 yrs of age whose parents both had asthma, also had asthma themselves. However, when extrapolated to the population as a whole, most children with asthma would have no parent with asthma. Risk factors suitable for secondary prevention, such as presence and persistence of food antibodies or early atopic dermatitis together with an atopic family history may predict up to 80% of aeroallergen sensitization by 5 yrs. However, the sensitivity of these factors is also low. We therefore need better predictors for asthma and a policy for intervention strategies according to age and risk.

Adult↗

Evidence for linkage of chromosome 12q15-q24.1 markers to high total serum IgE concentrations in children of the German Multicenter Allergy Study.

Linkage of asthma and high total serum IgE levels to chromosome 12q15-q24.1 has been recently described. To evaluate this region further in regard to total IgE responsiveness, we genotyped 52 unrelated German children with persistently "high" total serum IgE (selected from a noninterventional prospective multicenter cohort study) and their parents. We carefully defined a most extreme IgE phenotype and analyzed it as a dichotomous trait. We tested for linkage between high total IgE concentrations and nine polymorphic microsatellite markers on chromosome 12q15-q24.1 using the transmission/disequilibrium test. Evidence for linkage and allelic association for high total IgE was observed for four markers in this region. This study demonstrates the value of using extreme phenotypes in genetic analysis of a complex quantitative trait.

Child, Preschool↗

Sensitization to hen's egg at the age of twelve months is predictive for allergic sensitization to common indoor and outdoor allergens at the age of three years.

BACKGROUND: Specific predictors for atopic sensitization in early infancy are prerequisites for preventive intervention studies. OBJECTIVE: To identify predictors of allergic sensitization to common aeroallergens in infancy, 1314 children in five German cities were followed up from birth (1990) to the age of 3 years. METHODS: Blood samples were taken from cord blood and at follow-up visits at the ages of 1, 2, and 3 years. Total serum IgE and specific IgE antibodies to common food and inhalant allergens were determined. RESULTS: Among our study population, risk factors for sensitization to indoor and/or outdoor allergens at the age of 3 years were a positive family history, the presence of hen's egg-specific IgE antibodies (> or = 0.35 kU/L), and increased log- [total IgE] levels at the age of 12 months. Elevated cord blood IgE was not associated with sensitization to inhalant allergens at the age of 3 years. Egg-specific IgE greater than 2 kU/L in combination with a positive family history of atopy was a highly specific (specificity, 99%) and predictive (positive predictive value, 78%) marker for sensitization to inhalant allergens at 3 years of age. CONCLUSIONS: Hen's egg-specific IgE at the age of 12 months is a valuable marker for subsequent allergic sensitization to allergens that cause asthma, allergic rhinitis, and atopic dermatitis.

Allergens↗

Indoor allergen exposure is a risk factor for sensitization during the first three years of life.

BACKGROUND: The purpose of the study was to investigate the influence of environmental allergen exposure on allergic sensitization in infancy and early childhood. METHODS: A cohort of 1314 newborns was recruited and followed up prospectively at the ages 12, 24, and 36 months. The levels of major mite (Der p 1 and Der f 1) and cat (Fel d 1) allergens were determined from domestic carpet dust samples by sandwich ELISA. Specific serum IgE antibodies to mite and cat allergens were determined by CAP fluoroimmunoassay (Pharmacia). Logistic regression was used to assess the effects of allergen exposure, age, family history, and cord blood IgE simultaneously on the risk of sensitization. RESULTS: Children, who had been found to be sensitized at least once during the first 3 years of life, were found to be exposed to significantly higher house dust mite (median, 868 ng/gm vs 210 ng/mg; p = 0.001) and cat (median, 150 ng/gm vs 64 ng/gm; p = 0.011) allergen concentrations in domestic carpet dust compared with the group without sensitization. In homes with low (< or = 25th percentile) dust concentrations, the risk of sensitization to mite (1.6%), and cat (2.0%) is low, compared with 6.5% for mite and 6.3% for cat if the domestic exposure is above the 75th percentile. The dose-response relationships between allergen levels and sensitization indicate that the increase in sensitization risk at low allergen levels is more pronounced in cat allergy (p = 0.002) than in mite allergy (p = 0.026). In the group with a positive family history, lower mite and cat allergen concentrations are needed to achieve specific sensitization compared with the group with a negative family history. CONCLUSION: Our data indicate that avoidance measures in the domestic environment aimed at the primary prevention of allergen-driven sensitization should be introduced at the earliest possible stage, if possible during infancy.

Air Pollution, Indoor↗

Uptake of 169Yb complexes in normal and tumour cells: influence of ligand and metabolic cell activity and stability of cellular association.

For better understanding of the accumulation of trivalent radiometal tracers in tumours, studies of uptake of different 169Yb complexes into cultured normal (V79/4) and tumour (KTCTL-2) cells were performed. Cellular uptake of 169Yb3+ is dependent on both the metabolic activity of the cells and the nature of the ligand used. Uptake of 169Yb3+ from the citrate complex is an active cellular transport process but not tumour-specific. The 169Yb-aminopolycarboxylic acid complexes are taken up via a different, unknown mechanism, and in higher amounts by the tumour cells than by the V79/4 cell line, but the general features of uptake were principally the same with the normal and the tumour cells. Uptake of the complexes studied leads to a stable association of cellular components, which is a good premise for the therapeutic use of trivalent radiometals.

Animals↗

[Sleep behavior in the first 3 years of life].

A review of the literature on sleeping "disorders" in infants and toddlers shows that sleep problems are very common. We report the results of a German multicenter epidemiological study on a birth cohort (N = 1314). The children had medical examinations at 4 weeks, 3 months, 6 months, 1 year, 18 months, 2 years and 3 years. Most of the information on the sleeping behavior was gathered by structured interview and questionnaires. This paper gives information on the prevalence and the persistence of sleep problems in one to three year old children in Germany. Statistical analysis of correlations between breastfeeding and sleep and the place of sleep are reported. The consequences of sleep problems on the family overall well-being are also examined.

Child, Preschool↗

The natural course of sensitisation and atopic disease in infancy and childhood.

A number of epidemiological studies indicate that the prevalance of allergic airway diseases has been increasing over recent decades, especially in western industrialised countries, for reasons which are not yet completely understood (1, 2, 3). Changes in life style or an increase in indoor allergen exposure due to higher indoor temperature and humidity have been suggested as potential determinants, although evidence for both hypotheses is indirect (4). During the last years we have been following a birth cohort born in 1990 in order to understand the influence of the major genetic and environmental determinants, which are modulating the development of allergic sensitisation and the incidence of atopic symptoms. Sensitisation to indoor allergens has been demonstrated to be one of the major risk factors for the development of asthma in childhood (5, 6, 7, 8). Several cross-sectional studies in older children indicate that specific sensitisation to house dust mites is related to dust mite allergen concentrations in mattress dust (9, 10). Exposure threshold levels for several indoor allergens have been proposed, but individuals vary widely in their susceptibility to levels of exposure, and no absolute value has been identified which could generally ensure minimum risk.

Age Factors↗