Biomedical subjects

R Bergmann

Publications and source records attributed to R Bergmann.

At least 37 records · Page 2Linked to original sources

PubMed2001

Histamine challenges discriminate between symptomatic and asymptomatic children. MAS-Study Group. Multicentre Allergy Study.

The aims of this study were to investigate a threshold value for bronchial responsiveness in children aged 7 yrs, which discriminates between symptomatic and asymptomatic children, and to identify determinants of this responsiveness. Titrated bronchial histamine challenges using the reservoir method were performed in 645 children aged 7 yrs, from the birth cohort Multicentre Allergy Study (MAS). When defining a reference population of healthy children within the MAS cohort, the 95th percentile of the provocative concentration causing a 20% fall in forced expired volume in one second PC20 among these asymptomatic study subjects amounted to 0.60 mg x mL(-1). This resulted in a specificity of 93.0% and a sensitivity of 45.9%, for discriminating between "current wheezers" and "non-current wheezers". Determinants of airway responsiveness at this age were pulmonary function, sensitization to indoor allergens, total immunoglobulin E and current wheeze. The results indicate that a very low cut-off provocative concentration causing a 20% fall in forced expired volume in one second (<1.0 mg x mL(-1)) defines airway hyperresponsiveness in children aged 7 yrs using the reservoir method. Provocation protocols for histamine challenges in this age group should therefore start with concentrations markedly below 1.0 mg x mL(-1).

Allergens↗

PubMed2001

Intrauterine growth restriction induces up-regulation of cerebral aromatic amino acid decarboxylase activity in newborn piglets: [18F]fluorodopa positron emission tomographis study.

There is evidence that intrauterine growth restriction (IUGR) is associated with altered dopaminergic function in the immature brain. However, the relevant enzyme activities have not been measured in the living neonatal brain together with brain oxidative metabolism. Therefore, fluorine-18-labeled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) was used together with positron emission tomography to estimate the activity of the aromatic amino acid decarboxylase in the brain of 10 newborn IUGR piglets (2 to 5 d old; body weight, 908 +/- 109 g) and in 10 normal-weight (3 to 5 d old; body weight, 2142 +/- 373 g) newborn piglets. The regional transport of FDOPA to the brain and the clearance rate of labeled metabolites from brain tissue were broadly similar in the two groups. However, the regional rate constant for back flux from the brain was markedly increased in IUGR piglets for striatum (72%) and frontal cortex (83%) (p < 0.05). Furthermore, the rate constant for conversion of FDOPA to fluorodopamine was markedly increased (between 48% in cerebellum and 91% in mesencephalon, p < 0.05) in all brain regions of IUGR piglets studied. Thus, it is suggested that IUGR induces an up-regulation of aromatic amino acid decarboxylase activity that is not related to alterations in brain oxidative metabolism.

Animals↗

PubMed2001

Delayed hypersensitivity to tuberculin, total immunoglobulin E, specific sensitization, and atopic manifestation in longitudinally followed early Bacille Calmette-Guérin-vaccinated and nonvaccinated children.

BACKGROUND: Bacille Calmette-Guérin (BCG) is a strong T helper 1 incentive and, thus, may contribute to a decreased risk of T helper 2-dependent atopic disease. OBJECTIVE: To investigate the natural course of specific immunoglobulin E (IgE) responses and atopic disease in BCG-vaccinated and nonvaccinated children. PARTICIPANTS: Seven hundred seventy-four children from a prospectively followed birth cohort. OUTCOME MEASURES: Physical examination and case history were performed at 3, 6, 12, 18, 24, 36, 48, 60, 72, and 84 months of age. Total and specific serum IgE levels to 9 common inhalant and food allergens were determined (CAP; Pharmacia, Freiburg, Germany) at 12, 24, 36, 60, 72, and 84 months of age. Purified protein derivative (PPD) skin testing was performed at 84 months. RESULTS: Period and lifetime prevalences of atopic dermatitis and recurrent wheezing tended to be lower in the BCG-vaccinated group early in life, whereas no such trend was found after the second birthday or for allergic rhinitis. The proportion of children remaining free of clinical manifestations tended to be higher in the BCG-vaccinated group but differences decreased over time. No statistically significant differences were found for total IgE levels (median). Atopic sensitization tended to be lower among BCG-vaccinated children during the first 2 years of life. The diameter of the skin reaction to PPD did not correlate with total serum IgE. Clinical and serologic correlates of atopy were not significantly different between children with a skin test diameter of >/=5 mm and those with a smaller diameter. CONCLUSION: These results do not support the hypothesis that BCG vaccination in early infancy is associated with a subsequently markedly decreased risk of atopic sensitization or allergy. In addition, PPD skin test reactivity was not impaired in atopic individuals.

BCG Vaccine↗

PubMed2000

Early exposure to house-dust mite and cat allergens and development of childhood asthma: a cohort study. Multicentre Allergy Study Group.

BACKGROUND: In a prospective birth-cohort study, we assessed the relevance of mite and cat allergen exposure for the development of childhood asthma up to age 7 years. METHODS: Of 1314 newborn infants enrolled in five German cities in 1990, follow-up data at age 7 years were available for 939 children. Assessments included repeated measurement of specific IgE to food and inhalant allergens, measurement of indoor allergen exposure at 6 months, 18 months, and 3 years of age, and yearly interviews by a paediatrician. At age 7 years, pulmonary function was tested and bronchial hyper-responsiveness was measured in 645 children. FINDINGS: At age 7, the prevalence of wheezing in the past 12 months was 10.0% (94 of 938), and 6.1% (57 of 939) parents reported a doctor's diagnosis of asthma in their children. Sensitisation to indoor allergens was associated with asthma, wheeze, and increased bronchial responsiveness. However, no relation between early indoor allergen exposure and the prevalence of asthma, wheeze, and bronchial hyper-responsiveness was seen. INTERPRETATION: Our data do not support the hypothesis that exposure to environmental allergens causes asthma in childhood, but rather that the induction of specific IgE responses and the development of childhood asthma are determined by independent factors.

Air Pollution, Indoor↗

PubMed2000

Effects of the prototypical mGlu(5) receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine on rotarod, locomotor activity and rotational responses in unilateral 6-OHDA-lesioned rats.

In the present study, we evaluated the effect of the prototypical metabotropic glutamate receptor 5 (mGlu(5)) antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) on motor behaviour in rats using the accelerating rotarod, spontaneous locomotor activity and the 6-hydroxy-dopamine (6-OHDA) lesion model to assess its treatment potential for Parkinson's disease. The data indicate that MPEP at doses between 7.5 and 300 mg/kg, p.o. did not disrupt endurance performance on the accelerating rotarod (4-40 rpm in 300 s) which indicates that MPEP has a relatively high safety margin. However, while ineffective at doses of 3.75, 7.5 and 15 mg/kg (p.o.) MPEP inhibited spontaneous locomotor activity at doses of 30 and 100 mg/kg (p.o.). In the 6-OHDA rat rotation model, at doses of 7.5, 15 and 30 mg/kg (p.o.), MPEP induced a dose-dependent ipsilateral rotational response that reached statistical significance at the highest dose tested. This effect was relatively small but consistent. In combination with direct or indirect dopamine agonists, i.e. apomorphine (0.25 mg/kg, s.c.) and D-amphetamine (2.5 mg/kg, i.p.), MPEP (7.5, 15 or 30 mg/kg, p.o.) was found to significantly inhibit these dopamine receptor mediated rotational responses. MPEP injected at a dose of 30 mg/kg also inhibited the rotational response induced by L-DOPA (25 mg/kg, i.p.). (+)MK-801 was used in these rotation experiments as the reference compound. In view of these findings, it could be concluded that MPEP and potentially other mGlu(5) receptor antagonists are probably not appropriate drug candidates for the symptomatic treatment of Parkinson's disease.

Animals↗

PubMed2000

Does allergy in parents depend on allergy in their children? Recall bias in parental questioning of atopic diseases. Multicenter Allergy Study Group.

BACKGROUND: A positive atopic family history has proved to be one important risk factor for the development of atopic diseases in offspring. However, many epidemiologists are concerned about the accuracy and reliability of data because responses to questionnaires can be biased for many reasons. OBJECTIVE: The study investigated whether responses of parents questioned about their atopic diseases change depending on the development of atopic symptoms in their children. METHODS: During a prospective birth cohort study on atopy in children (the Multicenter Allergy Study) parents filled out questionnaires twice within 2 years about their atopic diseases. Differences between the 2 responses were examined by log-linear and logistic regression models depending on the diagnosed atopy status of the study children. RESULTS: Mothers tended to report more atopic diseases in the second questioning than in the first, indicating a nondifferential misclassification. Fathers were influenced by the development of atopic diseases in their children: they reported significantly more atopic diseases if the child developed atopic illness with atopic dermatitis. CONCLUSION: In parental questioning about atopic diseases, a recall bias must be considered for the association of atopic family history and atopy in children. Especially in case-control and cross-sectional studies, such misclassifications can result in biased estimates of prognosis and risk factors.

Child, Preschool↗

PubMed2000

Assessment of the in vitro and in vivo properties of a (99m)Tc-labeled inhibitor of the multidrug resistant gene product P-glycoprotein.

Overexpression of P-glycoprotein (Pgp), which is present in the plasma membrane of various tumor cells and in several normal cell types, contributes to the multidrug resistance (MDR) phenotype of many human cancers. As a prerequisite for therapy, the expression of Pgp must be studied. The available clinical radiopharmaceuticals for studying the expression of Pgp include the lipophilic (99m)Tc cations (sestamibi, tetrofosmin) as well as [(99m)Tc]Q57, [(99m)Tc]Q58, and [(99m)Tc]Q63. Here we describe the in vitro and in vivo properties of the structurally different complex (3-thiapentane-1, 5-dithiolato)[[N-(3-phenylpropyl)-N-2(3-quinazoline-2, 4-dionyl)-ethyl]amino-ethylthiolato¿ oxotechnetium(V) ((99/99m)Tc1) as a potential inhibitor of Pgp. (99)Tc1 enhances the net cell accumulation of Pgp substrates [(3)H]vinblastine, [(3)H]vincristine, [(3)H]colchicine, [(99m)Tc]sestamibi, and [(99m)Tc]tetrofosmin in rat brain endothelial cells (RBE4), an immortalized endothelial cell line that expresses Pgp. In addition, the cell accumulation of (99m)Tc1 could be increased by verapamil and reserpine, which are known Pgp inhibitors. A multitracer approach was used to study the side effects of (99)Tc1 on cell metabolism. The cells were simultaneously incubated with [(99m)Tc]sestamibi, 2-[(18)F]fluoro-2-deoxyglucose ([(18)F]FDG), and various (3)H-labeled tracers. Two-dimensional scatter plots of [(99m)Tc]sestamibi uptake/[(18)F]FDG uptake show typical changes of known Pgp inhibitors including (99)Tc1. The effects of (99)Tc1 on the in vivo distribution of [(99m)Tc]sestamibi and [(18)F]FDG in rats also are comparable with the effects of verapamil, an established Pgp inhibitor and calcium channel blocker. We conclude that (99/99m)Tc1 is a transport substrate and a potential inhibitor of Pgp. Our approach may be useful in the design of further radiotracers with specificity to Pgp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Functional expression of the serotonin transporter in immortalized rat brain microvessel endothelial cells.

There is evidence from recent studies that the brain endothelium (of capillaries and/or larger vessels) may serve as a specific target for serotonin [5-hydroxytryptamine (5-HT)]. This neurotransmitter is expected to be involved in the regulation of the blood-brain barrier (BBB) permeability and/or of the cerebral blood flow via receptor-mediated mechanisms. Effective control of these processes depends on a speedy uptake and metabolism of released 5-HT molecules. To realize this, a similar mechanism of 5-HT uptake as in brain may exist at the BBB. In this study, we have demonstrated using RT-PCR that 5-HT transporter mRNA is present in the brain endothelium and that a saturable transport system for 5-HT is functionally expressed in immortalized rat brain endothelial cells (RBE4 cells). These cells take up [3H]5-HT by an active saturable process with a Km value of 397 +/- 64 nmol/L and a transport capacity of 51.7 +/- 3.5 pmol x g(-1) x min(-1). The 5-HT uptake depends on Na+, as indicated by the replacement of NaCl by LiCl. The 5-HT uptake was sensitive to specific 5-HT transport inhibitors such as paroxetine, clomipramine, fluoxetine, and citalopram but not to inhibitors of the vesicular amine transporter such as reserpine or tetrabenazine. Our results demonstrate that cerebral endothelial cells are able to participate actively in the removal and metabolism of the released 5-HT, which supports the concept of direct serotoninergic regulation of the BBB function.

Animals↗

PubMed2000

Does lung retention of inhaled particles depend on their geometric diameter?

Experiments with a bolus technique suggest that retained fractions in the airways are dependent on the geometric diameter of the particles. This view has been adopted by the International Commission on Radiological Protection (ICRP) in its new human respiratory tract model (HRTM). The aim of the present study was to test this view by the use of an inhalation technique, in which particles with an aerodynamic diameter of about 6 microns are inhaled extremely (0.05 l/s) and as a result, the particles are deposited mainly in small ciliated airways. Nine healthy subjects inhaled on one occasion monodisperse 111In-labelled polystyrene particles (geometric diameter 6.05 microns, aerodynamic diameter 6.2 microns) and on another occasion monodisperse 111In-labelled Teflon particles (geometric diameter 4.47 microns, aerodynamic diameter 6.5 microns). Both particles were inhaled at 0.045 L/s and radioactivity in the body was measured after 0, 24, 48, and 72 hours as well as after 1, 2, and, for some subjects, also 3 weeks. The retention in the lungs at 24 hours was slightly lower for the Teflon particles (47%) than for the polystyrene particles (51%). From earlier experimental data with different particle sizes as well as from predictions with theoretical lung models, this difference is reasonably explained by the somewhat larger aerodynamic diameter of the Teflon particles. Clearance of the 2 particle types between 1 day and 2 weeks was similar within each individual as well as in the whole group. The differences between the clearance of 4.5 microns and 6 microns geometric diameter particles observed in the present experiment are significantly different (P < .01) from the differences seen in earlier shallow bolus experiments as well as from the differences for such particles calculated with the HRTM, i.e., our experiment does not support the hypothesis that the fraction retained after 1 day is dependent on the geometric diameter in the size range studied.

Administration, Inhalation↗

PubMed2000

The effect of heterogeneity of lung structure on particle deposition in the rat lung.

Differences in particle deposition patterns between human and rat lungs may be attributed primarily to their differences in breathing patterns and airway morphology. Heterogeneity of lung structure is expected to impact acinar particle deposition in the rat. Two different morphometric models of the rat lung were used to compute particle deposition in the acinar airways: the multiple-path lung (MPL) model (Anjilvel and Asgharian, 1995, Fundam. Appl. Toxicol. 28, 41-50) with a fixed airway geometry, and the stochastic lung (SL) model (Koblinger and Hofmann, 1988, Anat. Rec. 221, 533-539) with a randomly selected branching structure. In the MPL model, identical acini with a symmetric subtree (Yeh et aL, 1979, Anat. Rec. 195, 483-492) were attached to each terminal bronchiole, while the respiratory airways in the SL model are represented by an asymmetric stochastic subtree derived from morphometric data on the Sprague-Dawley rat (Koblinger et al., 1995, J. Aerosol. Med. 8, 7-19). In addition to the original MPL and SL models, a hybrid lung model was also used, based on the MPL bronchial tree and the SL acinar structure. Total and regional deposition was calculated for a wide range of particle sizes under quiet and heavy breathing conditions. While mean total bronchial and acinar deposition fractions were similar for the three models, the SL and hybrid models predicted a substantial variation in particle deposition among different acini. The variances of acinar deposition in the MPL model were consistently much smaller than those for the SL and the hybrid lung model. The similarity of acinar deposition variations in the two latter models and their independence on the breathing pattern suggests that the heterogeneity of the acinar airway structure is primarily responsible for the heterogeneity of acinar particle deposition.

Administration, Inhalation↗

PubMed2000

Comparison of clinical pathology parameters with two different blood sampling techniques in rats: retrobulbar plexus versus sublingual vein.

Blood samples were taken from the retrobulbar venous plexus or the sublingual vein of male HamIbm:Wist rats to compare clinical pathology parameters between the two sampling techniques. By analogy with a pharmacokinetic study, blood was sampled six times during one day from unfasted animals. After 3 weeks of recovery, blood was taken from fasted animals on a single occasion. In addition, prolactin and corticosterone levels were determined to compare stress-related effects between the two sampling methods. Body weight development and food consumption were similar after single as well as after repeated blood sampling for the two blood sampling techniques. Haemotological evaluation showed a gradual decrease in erythrocyte count, haemoglobin concentration and haematocrit after repeated blood sampling. Repeated withdrawal of blood samples over 24 h corresponding to approximately 22% of the total blood volume resulted in a decrease in red blood cell parameters by up to 30%. The withdrawal of approximately 10% of the total blood volume was associated with a decrease in these parameters by up to 10% and should not be exceeded for animal welfare reasons and to allow a reliable evaluation of data in a study. Repeated blood sampling was associated with an initial decrease in the number of white blood cells, mainly due to a reduction in lymphocytes; white blood cell counts were slightly increased one day after. The decrease in lymphocytes and the increase in neutrophils after repeated sampling were generally slightly more pronounced in the blood from the retrobulbar plexus than from the sublingual vein. Comparison of serum clinical chemistry data showed significantly higher activities of creatine kinase and aspartate aminotransferase in samples from the retrobulbar plexus. These findings suggest a higher degree of tissue damage with blood sampling from the retrobulbar plexus than from the sublingual vein. Despite a large inter-individual variability, higher mean values of prolactin on each occasion and corticosterone after a single sample in fasted animals indicate a higher stress associated with blood sampling from the retrobulbar plexus.

Amylases↗

PubMed2000

Relation between brain tissue pO2 and dopamine synthesis of basal ganglia--a 18FDOPA-PET study in newborn piglets.

Perinatal hypoxic-ischemic cerebral injury is a major determinant of neurologic morbidity and mortality in the neonatal period and later in childhood. There is evidence that the dopaminergic system is sensitive to oxygen deprivation. However, the respective enzyme activities have yet not been measured in the living neonatal brain. In this study, we have used 18F-labelled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) together with positron emission tomography (PET) to estimate the activity of the aromatic amino acid decarboxylase (AADC), the ultimate enzyme in the synthesis of dopamine, in the brain of newborn piglets under normoxic and moderate asphyxial conditions. The study was performed on 8 newborn piglets (2-5 days old). In each piglet PET studies were performed under control conditions and during 2-hour asphyxia. Simultaneously, brain tissue pO2 was recorded, cerebral blood flow (CBF) was measured with colored microspheres and cerebral metabolic rate of oxygen (CMRO2) was determined. Asphyxia was induced by lowering the inspired fraction of oxygen from 0.35 to 0.10 and adding about 6% CO2 to the inspired gas. Asphyxia elicited a more than 3-fold increase of the CBF (p < 0.01) so that CMRO2 remained unchanged throughout the asphyxial period. Despite this, brain tissue pO2 was reduced from 19 +/- 4 mm Hg to 6 +/- 3 mm Hg (p < 0.01). Blood-brain transfer of FDOPA as well as permeability-surface area product (PS) from striatum were unchanged. Striatal synthesis rate of fluoro-dopamine from FDOPA (k3) was, however, significantly increased (p < 0.01). This increase of the AADC activity is associated with reduced brain tissue pO2. Asphyxia-induced CBF increase impedes an alteration of brain oxidative metabolism.

Animals↗

PubMed1999

Regional distribution of cerebral blood volume and cerebral blood flow in newborn piglets--effect of hypoxia/hypercapnia.

The relationship between regional parenchymal cerebral blood volume (CBV), regional cerebral blood flow (CBF) and the calculated mean transit time (MTT) was investigated in 14 newborn piglets. The effects of combined hypoxic hypoxia (PaO2 = 32 +/- 5 mm Hg) and hypercapnia (paCO2 = 68 +/- 5 mm Hg) were measured in seven animals. Remaining animals served as the control group. During baseline conditions the highest CBF and CVB values were found in the lower brainstem and cerebellum, whereas white matter exhibited the lowest values (p < 0.05). MTT was prolonged within the cerebral cortex (2.34 +/- 0.42 s-1) compared with the thalamic MTT (1.53 +/- 0.38 s-1) (p < 0.05). Under moderate hypoxia/hypercapnia, a CBF increase to the forebrain (p < 0.05) resulted in an elevated brain oxygen delivery (p < 0.05) and so CMRO2 remained unchanged. Moreover, a moderate increase of CBV and a marked shortening of MTT occurred (p < 0.05). The CBV increase was higher in structures with lowest baseline values, i.e., thalamus (66% increase) and white matter (62% increase) (p < 0.05). MTT was between 22% of baseline in the lower brainstem and 49% in white matter (p < 0.05). We conclude that under normoxic and normocapnic conditions the newborn piglets exhibit a comparatively enlarged intraparenchymal CBV. Moderate hypoxia and hypercapnia induced a marked increase in cerebral blood flow which appears to be caused by an increased perfusion velocity, expressed by a strongly reduced mean transit time and by a concomitant CBV increase.

Animals↗

PubMed1999

Upregulation of the aromatic amino acid decarboxylase under neonatal asphyxia.

Perinatal hypoxic-ischemic cerebral injury is a major determinant of neurologic morbidity and mortality in the neonatal period and later in childhood. There is evidence that the dopaminergic system is sensitive to asphyxia. However, the respective enzyme activities have not yet been measured in the living neonatal brain. In this study, we have used 18F-labeled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) together with positron-emission tomography (PET) to estimate the activity of the aromatic amino acid decarboxylase (AADC), the ultimate enzyme in the synthesis of dopamine (DA), in the brain of newborn piglets. Simultaneously, the cerebral blood flow (CBF) was measured with colored microspheres. Asphyxia elicited an up to threefold increase of the CBF. Despite this, the blood-brain transfer of FDOPA as well as the clearance rate constants from brain were unchanged. However, the synthesis rate of FDA from FDOPA was significantly increased in frontal cortex, striatum, and midbrain. This increase of the AADC activity and the decrease of monoamine oxidase activity may contribute to the increase of extracellular DA during asphyxia which is expected to be involved in severe disturbances of neuronal metabolism, e.g., by generating free radicals.

Algorithms↗

PubMed1999

Serum IgE levels during the first 6 years of life.

OBJECTIVE: Total serum IgE percentiles were derived for a population-based sample of 4082 white children from Germany by weighted analysis of measurements from the Multicenter Allergy Study cohort. METHODS: The children of a prospective birth cohort were selected from a complete 1-year sample of newborns in 6 obstetric departments in 1990. Total IgE was determined at 1, 2, 3, 5, and 6 years of age in 1160 newborns of the cohort. By weighting these measurements for sex, atopic family history, and elevated cord blood IgE, total serum IgE percentiles were estimated for the original population-based sample of 4082 children. RESULTS: IgE levels increased by age (P <.0001). We found statistically significant higher total IgE values in boys than in girls at each age (P <.05). Within the group of atopic children, this sex difference was not statistically significant. CONCLUSION: Our estimates of total serum IgE levels for a large population-based sample were lower than most values previously reported. We suggest that for both clinical and epidemiologic and genetic studies, IgE values should be expressed with percentiles.

Aging↗

PubMed1999

Natural course of sensitization to food and inhalant allergens during the first 6 years of life.

BACKGROUND: Specific IgE antibody responses to alimentary and environmental allergens are one of the hallmarks of atopic diseases. The knowledge of the time course of allergic sensitization during early life may facilitate measures for preventive interventions. OBJECTIVE: In a prospective birth cohort study (the Multicenter Allergy Study [MAS]) we investigated annual incidence and prevalence rates of sensitization to food and inhalant allergens during the first 6 years of life. METHODS: For 216 children of a prospective birth cohort (MAS), a complete follow-up of specific IgE measurements to 9 food and inhalant allergens was available at 1, 2, 3, 5, and 6 years of age. On the basis of these measurements, sensitization rates were estimated for the reference population of 4082 children by weighted analysis. RESULTS: Annual incidence rates of sensitization to food allergens decreased from 10% at 1 year of age to 3% at the 6 years of age. Incidences of sensitization to inhalant allergen, however, increased with age (from 1.5% at 1 year to 8% at 6 years). Point prevalences of allergic sensitization to at least 1 of the 9 tested allergens increased from 11% at 1 year up to 30% at 6 years. This increase was due to markedly increasing sensitization rates to inhalant allergens (1.5% to at least 1 inhalant allergen at 1 year and 26% at 6 years of age), whereas sensitization rates to food allergens remained stable during the first 6 years of life (10%). CONCLUSION: The earliest serologic marker for atopic immunoreactivity in infancy is the presence of IgE antibodies to egg, followed by milk. The development of sensitization to inhalant allergens occurs mostly after infancy. Beyond the third birthday annual incidence and prevalence increase markedly with age. Rates for outdoor allergens are twice those for indoor allergens.

Air Pollutants↗

PubMed1999

Peripheral inflammation increases the capsaicin sensitivity of dorsal root ganglion neurons in a nerve growth factor-dependent manner.

Inflammation results in a local increase in nerve growth factor production which potentially can modify the properties of nerve growth factor-responsive sensory neurons innervating the inflamed tissue. The sensitivity of primary sensory neurons to the neurotoxin capsaicin is regulated in vitro by nerve growth factor and we have now investigated the effect of complete Freund's adjuvant-induced inflammation on the capsaicin sensitivity of adult rat sensory neurons. Dorsal root ganglion neurons innervating inflamed tissue were identified in vivo by retrograde labelling with the dye Fast Blue. Neuronal capsaicin sensitivity was measured in vitro with a quantitative cobalt-uptake densitometric technique, and was shown to increase significantly five days after inflammation. This increase in sensitivity was dependent on nerve growth factor as it could be inhibited by systemic treatment with nerve growth factor neutralizing antibodies. The enhanced capsaicin sensitivity that results from Freund's adjuvant injection may contribute to inflammatory hyperalgesia.

Amidines↗

PubMed1999

Effect of pre- and postnatal tobacco smoke exposure on specific sensitization to food and inhalant allergens during the first 3 years of life. Multicenter Allergy Study Group, Germany.

BACKGROUND: The study aimed to assess the effect of pre- and postnatal tobacco smoke exposure on specific sensitization to food allergens and inhalant allergens during the first 3 years of life. METHODS: A total of 342 children of a prospective and observational birth cohort study on atopy (MAS) were included on the basis of a complete follow-up of specific IgE measurements at the ages of 1, 2, and 3 years with available questionnaire information about the parental smoking habit at birth, 18 months, and 3 years of age. Study children were grouped into four exposure categories representing in utero and postnatal environmental tobacco smoke (ETS) exposure, and according to the number of cigarettes smoked by the parents. The effect on the development of allergic sensitization to food, outdoor, and indoor allergens by 3 years of age was determined by multiple logistic regression analyses. RESULTS: At the age of 3, children who were pre- and postnatally exposed to tobacco smoke had a significantly higher risk of sensitization to food allergens (odds ratio: 2.3, 95% C.I.: 1.1-4.6) than unexposed children. Children who were only postnatally exposed by a smoking mother also had a 2.2 times higher risk (95% C.I.: 0.9-5.9) of sensitization than unexposed children. These two categories (pre- and/or postnatal exposure) contribute to the significant overall effect of the tobacco smoke exposure (P< or =0.02). No significant association between tobacco smoke exposure and specific sensitization to inhalant allergens was observed. The determining risk factors for this type of sensitization were atopic family history and mite- and cat-allergen exposure levels. CONCLUSIONS: During the first 3 years of life, both prenatal and postnatal tobacco smoke exposure has an adjuvant effect on allergic sensitization which seems to be restricted to allergens to which children are mainly exposed, in combination with the peak of the ETS exposure around the first birthday.

Child, Preschool↗