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Biomedical subjects

S Koletzko

Publications and source records attributed to S Koletzko.

At least 19 recordsLinked to original sources
PubMed2006

Respiratory health and individual estimated exposure to traffic-related air pollutants in a cohort of young children.

OBJECTIVES: To estimate long-term exposure to traffic-related air pollutants on an individual basis and to assess adverse health effects using a combination of air pollution measurement data, data from geographical information systems (GIS) and questionnaire data. METHODS: 40 measurement sites in the city of Munich, Germany were selected at which to collect particulate matter with a 50% cut-off aerodynamic diameter of 2.5 microm (PM2.5) and to measure PM2.5 absorbance and nitrogen dioxide (NO2). A pool of GIS variables (information about street length, household and population density and land use) was collected for the Munich metropolitan area and was used in multiple linear regression models to predict traffic-related air pollutants. These models were also applied to the birth addresses of two birth cohorts (German Infant Nutritional Intervention Study (GINI) and Influence of Life-style factors on the development of the Immune System and Allergies in East and West Germany (LISA)) in the Munich metropolitan area. Associations between air pollution concentrations at birth address and 1-year and 2-year incidences of respiratory symptoms were analysed. RESULTS: The following means for the estimated exposures to PM2.5, PM2.5 absorbance and NO2 were obtained: 12.8 microg/m3, 1.7x10(-5) m(-1) and 35.3 mug/m3, respectively. Adjusted odds ratios (ORs) for wheezing, cough without infection, dry cough at night, bronchial asthma, bronchitis and respiratory infections indicated positive associations with traffic-related air pollutants. After controlling for individual confounders, significant associations were found between the pollutant PM2.5 and sneezing, runny/stuffed nose during the first year of life (OR 1.16, 95% confidence interval 1.01 to 1.34) Similar effects were observed for the second year of life. These findings are similar to those from our previous analysis that were restricted to a subcohort in Munich city. The extended study also showed significant effects for sneezing, running/stuffed nose. Additionally, significant associations were found between NO2 and dry cough at night (or bronchitis) during the first year of life. The variable "living close to major roads" (<50 m), which was not analysed for the previous inner city cohort with birth addresses in the city of Munich, turned out to increase the risk of wheezing and asthmatic/spastic/obstructive bronchitis. CONCLUSIONS: Effects on asthma and hay fever are subject to confirmation at older ages, when these outcomes can be more validly assessed.

Air Pollutants↗
PubMed2006

Prospective multicentre study on antibiotic resistance of Helicobacter pylori strains obtained from children living in Europe.

AIM: To prospectively assess the antibacterial resistance rate in Helicobacter pylori strains obtained from symptomatic children in Europe. METHODS: During a 4-year period, 17 paediatric centres from 14 European countries reported prospectively on patients infected with H pylori, for whom antibiotic susceptibility was tested. RESULTS: A total of 1233 patients were reported from Northern (3%), Western (70%), Eastern (9%) and Southern Europe (18%); 41% originated from outside Europe as indicated by mother's birth-country; 13% were <6 years of age, 43% 6-11 years of age and 44% >11 years of age. Testing was carried out before the first treatment (group A, n = 1037), and after treatment failure (group B, n = 196). Overall resistance to clarithromycin was detected in 24% (mean, A: 20%, B: 42%). The primary clarithromycin resistance rate was higher in boys (odds ratio (OR) 1.58; 1.12 to 2.24, p = 0.01), in children <6 years compared with >12 years (OR 1.82, 1.10 to 3.03, p = 0.020) and in patients living in Southern Europe compared with those living in Northern Europe (OR 2.25; 1.52 to 3.30, p<0.001). Overall resistance rate to metronidazole was 25% (A: 23%, B: 35%) and higher in children born outside Europe (A: adjusted. OR 2.42, 95% CI: 1.61 to 3.66, p<0.001). Resistance to both antibiotics occurred in 6.9% (A: 5.3%, B: 15.3%). Resistance to amoxicillin was exceptional (0.6%). Children with peptic ulcer disease (80/1180, 6.8%) were older than patients without ulcer (p = 0.001). CONCLUSION: The primary resistance rate of H pylori strains obtained from unselected children in Europe is high. The use of antibiotics for other indications seems to be the major risk factor for development of primary resistance.

Adolescent↗
PubMed2006

Pharmacokinetics and pharmacodynamic action of budesonide in children with Crohn's disease.

BACKGROUND: Budesonide is effective as initial therapy of mild to moderate Crohn's disease in adults. Superior tolerability to conventional corticosteroids might be attributed to extensive first-pass metabolism of budesonide by cytochrome P450 3A. AIM: To evaluate biotransformation and pharmacodynamic action of budesonide in children. METHODS: Drug disposition and effects on endogenous cortisol were evaluated in 12 children with Crohn's disease (5-15 years) after first intake of 3 mg budesonide (single dose), and again after 1 week of thrice daily dosing (steady-state). The parent drug and cytochrome P450 3A-dependent metabolites were analysed in blood and urine. RESULTS: Pharmacokinetic parameters of budesonide following single-dose administration (e.g. AUC(0-infinity) 7.7+/-5.1 h ng/mL, C(max) 1.8+/-1.2 ng/mL) did not change upon multiple dosing. Overall systemic elimination of budesonide reflected by clearance and half-life was not different between children and adults. After 1 week of treatment reversible adrenal suppression was observed - most pronounced in children aged below 12 years. CONCLUSIONS: Disposition of oral budesonide appears to be similar between children and adults, but the doctor has to be aware of an increased risk for adrenal suppression in paediatric patients.

Administration, Oral↗
PubMed2006

[Blue rubber-bleb nevus syndrome and therapeutic double balloon enteroscopy].

This is the first report about the endoscopic removal of hemangiomas in the gastrointestinal tract using the double-balloon enteroscopic technique. We report on a 16-year-old female patient with a 10-year history of chronic anemia due to recurrent gastrointestinal bleeding. Besides permanent iron substitution, up to 3 blood transfusions per week are necessary. At birth a blue rubber-bleb nevus syndrome was diagnosed, with blue angiomatous lesions preferring her skin and digestive tract. In the 8 years before admittance numerous conventional endoscopic procedures and one intraoperative endoscopy with laser coagulation of many cavernous hemangiomas were performed. In our department the successful treatment of 150 hemangiomas with argon plasma coagulation or polypectomy in combination with double-balloon enteroscopy and conventional endoscopy was achieved without complications.

Adolescent↗
PubMed2004

Caesarean section and gastrointestinal symptoms, atopic dermatitis, and sensitisation during the first year of life.

AIMS: To investigate the effect of caesarean section on gastrointestinal symptoms, atopic dermatitis, and sensitisation to nutritional allergens in infants. METHODS: A total of 865 healthy full term neonates with parental history of allergy participating in the prospective German Infant Nutritional Intervention Program (GINI) were exclusively breast fed during the first four months of life and had a one year follow up. Data were obtained by follow up visits at age 1, 4, 8, and 12 months, weekly diaries for the first six months, and measurement of total and specific IgE at birth and 12 months. RESULTS: Infants born by caesarean section (147/865, 17%) had a greater risk of diarrhoea (OR(adj) 1.46, 95% CI 1.022 to 2.10) and sensitisation to food allergens, both in adjusted (OR(adj) 2.06, 95% CI 1.123 to 3.80) and stratified analyses (by cord blood IgE). Caesarean delivery was not associated with colicky pain and atopic dermatitis. CONCLUSION: Caesarean delivery might be a risk factor for diarrhoea and sensitisation in infants with family history of allergy. Further research in this area seems warranted as choosing caesarean section becomes increasingly popular.

Adult↗
PubMed2003

Chemokine receptor 5 expression in gastric mucosa of Helicobacter pylori-infected and noninfected children.

Experimental data from human adults or animal models indicate that the Helicobacter pylori-specific immune response is dominated by inflammatory T cells of the Th1 type. To investigate whether a Th1 immune response is established in early H. pylori infection, gastric biopsy samples from 70 children were subjected to immunohistochemical analysis. To this end, T cells, B cells, monocytes, neutrophils, and chemokine receptor 5 (CCR5)-expressing (CCR5(+)) cells, which are associated with Th1 immune responses, were quantified. Children were classified according to H. pylori status and clinical, laboratory, and macroscopic (during endoscopy) findings, without knowledge of histological findings. Group 1 included 31 H. pylori-infected children, group 2 contained 24 children with other conditions possibly affecting the stomach, and group 3 contained 15 children without verifiable pathological findings in the stomach. Lymphoid follicles were present in 90% of biopsy samples from group 1 and 48% of those from group 2 but absent in group 3 biopsy samples. Intraepithelial T cells and CCR5(+) cells were regularly detected in all groups without significant differences. B cells, monocytes, and neutrophils were not found. In contrast, the numbers of lamina propria T cells (P < 0.003) and CCR5(+) cells (P < 0.001) were increased significantly in H. pylori-infected children. B cells (in 13 of 66 children) were detected in children with active (n = 11) or previously cleared (n = 2) H. pylori infections but were absent in healthy children. The numbers of monocytes (in 10 of 67 children) did not differ among the groups. Calculations indicated that the majority of gastric T cells express CCR5; this finding is in contrast to the low percentage of CCR5(+) T cells in the peripheral circulation. Thus, an increase in the numbers of CCR5(+) cells in H. pylori-infected stomach mucosa suggests that this molecule may play an important role in gastric immune responses.

Adolescent↗
PubMed2003

Evaluation of a novel monoclonal enzyme immunoassay for detection of Helicobacter pylori antigen in stool from children.

BACKGROUND: Reliable non-invasive methods for detection of Helicobacter pylori infection are required to investigate the incidence, transmission, and clearance of infection in childhood. AIM: To evaluate a new monoclonal enzyme immunoassay (EIA) (FemtoLab H pylori Cnx) for detection of H pylori antigen in stool in a large cohort of children compared with invasive diagnostic methods and the (13)C urea breath test. PATIENTS AND METHODS: A total of 302 symptomatic previously untreated children (aged 0.5-18.7 years; 148 girls) were recruited at three centres. H pylori status was defined by results of culture, histology, the rapid urease test, and the (13)C urea breath test. Stool samples were investigated locally by the EIA using two different production lots. According to the manufacturer's recommendations, an optical density (OD) of 0.150 was used as a cut off value. RESULTS: OD values clearly differentiated between the 92 H pylori infected and the 210 non-infected children (median (5th-95th percentiles) 2.729 (0.232->4.000) v 0.021 (0.009-0.075)). Only two false positive and two false negative results occurred, giving a sensitivity, specificity, positive predictive value, and negative predictive value of 98%, 99%, 98%, and 99%, respectively. No significant relation was found between age and OD values in infected or non-infected children. CONCLUSIONS: The monoclonal stool antigen EIA was excellent in diagnosing H pylori infection in symptomatic children. Accuracy was independent of the laboratory, production lot used, or the child's age. Because only 18/116 children <6 years of age were infected with H pylori, further validation of the test is needed in young infected children.

Adolescent↗
PubMed2002

Fluorescence in situ hybridization vs. epsilometer test for detection of clarithromycin-susceptible and clarithromycin-resistant Helicobacter pylori strains in gastric biopsies from children.

AIM: To compare the results of culture and epsilometer test with fluorescence in situ hybridization for the detection of Helicobacter pylori and the presence of clarithromycin-susceptible and clarithromycin-resistant strains in antral biopsies from children. METHODS: Antral biopsies from 149 unselected children were investigated prospectively; 15 had previously received anti-H. pylori therapy. H. pylori status was defined by histology, rapid urease test and 13C-urea breath test. Fluorescence in situ hybridization was applied on fresh tissue with probes specific for the clarithromycin-susceptible wild type and three clarithromycin-resistant mutants. Susceptibility to clarithromycin was tested by epsilometer test in two laboratories. RESULTS: Culture and fluorescence in situ hybridization gave negative results in all 66 H. pylori-negative children (specificity, 100%). Of 83 infected children, cultures were successful in 75 (90%), epsilometer test in 71 (86%) and fluorescence in situ hybridization in 77 (93%). Eleven children (13%) showed discrepant results between the applied methods, indicating mixed infection. Clarithromycin-resistant isolates were identified in 16 of 73 previously untreated children. CONCLUSIONS: Primary resistance to clarithromycin is common (22%) in H. pylori isolates from children living in Germany. Fluorescence in situ hybridization is an excellent, fast method for the detection of H. pylori and clarithromycin-resistant mutants in gastric biopsies. Multiple biopsies identify mixed infections, indicating that clarithromycin-resistant and clarithromycin- susceptible strains are not evenly distributed within the stomach.

Adolescent↗
PubMed2002

Maternal compliance with nutritional recommendations in an allergy preventive programme.

AIMS: To assess maternal compliance with nutritional recommendations in an allergy preventive programme, and identify factors influencing compliance behaviour. METHODS: Randomised double-blind intervention study on the effect of infant formulas with reduced allergenicity in healthy, term newborns at risk of atopy. Maternal compliance with dietary recommendations concerning milk and solid food feeding was categorised. RESULTS: A total of 2252 newborns were randomised to one of four study formulas. The drop out rate during the first year of life was 13.5% (n = 304). The rates of high, medium, and low compliance to milk feeding during weeks 1-16 were 83.4%, 4.0%, and 7.5%; the corresponding rates to solid food feeding during weeks 1-24 were 60.0%, 12.1%, and 22.9%. In 5.1% of subjects no nutritional information was available. Low compliance was more frequent among non-German parents, parents with a low level of education, young mothers, smoking mothers, and those who weaned their infant before the age of 2 months. CONCLUSIONS: Evaluation of allergy preventive programmes should take into account non-compliance for assessing the preventive effectiveness on study outcome.

Adult↗
PubMed2001

Dumping syndrome: a common problem following Nissen fundoplication in young children.

Within a 3-year period we observed six children, aged 3 months to 4 years, with dumping syndrome (DS) following Nissen fundoplication. Five were neurologically normal and one was slightly mentally retarded. Symptoms included postprandial tachycardia, diaphoresis, lethargy, severe retching, meteorism or gas-bloat syndrome, watery diarrhea, refusal to eat with failure to thrive, and developmental delay. Results of an oral glucose tolerance test did not correlate with the severity of symptoms. In one child severe retching led to recurrent paraesophageal gastric herniation, necessitating two reoperations and a gastrostomy. A lack of meal stimulated pancreatic polypeptide release in this patient indicated vagal damage. Initially five of the six children needed continuous intragastric feeding until bolus application of a carbohydrate-modified diet was tolerated. We conclude that the diagnosis of DS is often delayed in spite of characteristic clinical signs. Intensive postoperative follow-up after antireflux surgery should be mandatory in children.

Child, Preschool↗
PubMed2001

Nutritional challenges of infants with cystic fibrosis.

Nutrition plays an essential role in the management of cystic fibrosis (CF), particularly in infants with their high energy requirement due to rapid growth. Most infants are already malnourished at the time of clinical diagnosis due to an energy imbalance with increased losses and needs not compensated by energy intake. Even in very young asymptomatic CF patients diagnosed by neonatal screening programs, nutritional deficits can be detected in a high proportion of infants, since about half of all CF patients have evidence of pancreatic insufficiency at the time of birth. This review provides recommendations for assessment of the nutritional status at diagnosis and nutritional management including supplementation with pancreatic enzymes during the first year of life.

Cystic Fibrosis↗
PubMed2001

Evaluation of a rapid whole blood test to detect Helicobacter pylori infection in children.

BACKGROUND: Rapid, patient near tests for detecting antibodies against Helicobacter pylori are offered for clinical use. We evaluated the BM-Test (Boehringer Mannheim, Germany; identical to the Helisal Rapid Blood Test) in children with recurrent abdominal pain. METHODS: The BM-Test and 13C-urea breath test (UBT) were performed in 195 children (4-18 years). Symptoms were assessed using a 4-week diary. Upper endoscopy was performed in all UBT-positive children and in UBT-negative children with symptoms suggestive of organic disease. H. pylori status was considered positive if at least two of three methods (UBT, histology or rapid urease test) or culture were positive. RESULTS: After exclusion of children with previous H. pylori therapy (n = 8) and undetermined H. pylori status (n = 1), 61/186 (33%) children were H. pylori positive. The BM-Test in relation to H. pylori status revealed a sensitivity of 54%, specificity of 90%, a likelihood ratio of 5.2 for a positive, and of 0.4 for a negative test result. Accuracy of the test was independent of ethnicity, gender, age, family history for ulcer disease, frequency or severity of abdominal symptoms, epigastric tenderness, type of blood sampling (capillary versus venous) and DOB values of the UBT. In eight previously treated children, the test gave one false-positive and three false-negative results. CONCLUSIONS: Almost half of H. pylori-infected children and 10% of non-infected children were misclassified by the BM-Test. False-negative results are not related to young age or certain ethnic groups. The poor performance makes the test unsuitable for epidemiological and clinical use in children.

Adolescent↗
PubMed2001

Infants differ from teenagers: use of non-invasive tests for detection of Helicobacter pylori infection in children.

Reliable non-invasive tests that are feasible in early childhood are essential to the study of transmission of Helicobacter pylori, since most individuals get infected during the first years of life. New tests are validated by comparison with a "gold standard", but no single test for detection of H. pylori infection can be used as a fully reliable reference method. Therefore, concordant results of at least two biopsy-based tests (histology, culture, rapid urease test) are considered as the "gold standard". Most of the validation studies in children included only a few infants and toddlers, with low numbers particularly for H. pylori-infected individuals. Only when increasing numbers of patients were tested and separated into subgroups by age it became apparent that the accuracy of most tests is lower in young children if the same cut-off values are used as established for older children or adults. Therefore, statements such as "a test has been validated with good results in children" must be interpreted with caution, unless different age groups are considered with sufficient numbers of infected and non-infected children in each age group.

Adolescent↗
PubMed2001

Evaluation of the Helicobacter pylori stool antigen test (HpSA) for detection of Helicobacter pylori infection in children.

OBJECTIVE: Helicobacter pylori (H. pylori) infection is usually acquired in early childhood. Noninvasive methods for detection of H. pylori infection are required to study its incidence, transmission, and clearance. They should be easy to perform, inexpensive, and have a high diagnostic accuracy, especially in infants and toddlers. Both serology and the 13C-urea breath test (13C-UBT) do not fulfill all these requirements. The aim of this study was to evaluate a new enzyme immunoassay for detection of H. pylori antigen in stool (Premier Platinum HpSA, Meridian Diagnostics, Cincinnati, OH) in a large cohort of children and to compare it to invasive techniques and the 13C-UBT. METHODS: HpSA was performed in 310 stool samples of 274 children divided into three groups. Group A consisted of 145 children and adolescents (0.5-19.8 yr, 66/145 <6 yr) who underwent upper endoscopy for various gastrointestinal symptoms. H. pylori status was defined by histology, culture, and rapid urease test from biopsies of the antrum and corpus. A 13C-UBT was performed in 133 of 145 children. Group B consisted of 22 patients (5.7-16.1 yr) who were retested with both noninvasive tests 8 wk after anti-H. pylori triple therapy. Group C consisted of 129 healthy infants and toddlers (0.9-3.1 yr) who were tested with the 13C-UBT. Children with discrepant or positive test results were retested after 2 and 12 months. Results of the HpSA were read at 450/620 nm by spectrophotometry. An optical density <0.100 was defined as negative, >0.120 as positive, and values between 0.100 and 0.120 were considered as equivocal. RESULTS: In Group A, the HpSA gave false-negative results in five of 45 infected children and false-positive results in four of 100 noninfected children, whereas four patients (2.8%) showed equivocal results. In both infected and noninfected children, no relation between the optical density values and age was found. The 13C-UBT was correct in 132 of 133 children tested. In Group B, there was complete concordance between the HpSA and 13C-UBT: 19 children tested negative and three positive. In Group C, concordant results between the two noninvasive methods were found in 124 of 129 (96%) toddlers (122 negative and two positive). Retesting of five children with discrepant results revealed that, on initial testing, the HpSA was incorrect in two (one false-positive, one false-negative), and the 13C-UBT was incorrect in three (always false-positive). CONCLUSIONS: In symptomatic children, the HpSA revealed a sensitivity of 88.9% (95% CI 77.3-96.3) and a specificity of 94.0% (88.1-97.7) compared to the 13C-UBT, 100% (94.0-100) and 98.9% (94.7-100), respectively. However, in healthy toddlers, the HpSA performed as well as the 13C-UBT with excellent concordance between the two noninvasive tests. There was no age dependency of the stool test results, and changing the cutoff would not have improved accuracy. Thus, the HpSA test seems suitable to monitor the success of anti-H. pylori therapy.

Adolescent↗
PubMed2001

Comparison of fluorescent in situ hybridization and conventional culturing for detection of Helicobacter pylori in gastric biopsy specimens.

In this study, we have investigated 201 gastric biopsy specimens obtained from dyspeptic patients for the presence of Helicobacter pylori. By means of fluorescent in situ hybridization (FISH) with rRNA-targeted fluorescence-labeled oligonucleotide probes specific for H. pylori, this pathogen was detected in 63 biopsy specimens. By using conventional culturing, H. pylori was isolated from 49 of these 63 gastric biopsy specimens. In contrast, FISH failed to identify H. pylori in four samples from which the pathogen was cultured. The lowest sensitivity was obtained by using the urease test. H. pylori was detected indirectly by this method in 43 of 67 biopsy specimens, which were positive for the pathogen as determined by FISH and/or culturing. All 49 H. pylori isolates that were detected by FISH and culturing underwent antimicrobial susceptibility testing for clarithromycin, a macrolide drug that is a key component in the therapy of peptic ulcer disease caused by this pathogen. Clarithromycin susceptibility testing of cultured isolates was carried out by the E-test, whereas FISH was used on biopsy specimens to detect clarithromycin-resistant mutant strains. No discrepancies were found between these two methods. Thirty-seven strains were clarithromycin sensitive, and eight H. pylori isolates were resistant to the macrolide. From another four biopsy specimens, a mixture of clarithromycin-sensitive and -resistant strains was identified by both methods. Thus, FISH is a reliable technique for determining the clarithromycin susceptibility of this pathogen. Taken together, FISH is a more sensitive and rapid technique than culturing for detection of H. pylori in gastric biopsy specimens. However, in the microbiology routine diagnostic laboratory, the combination of both FISH and conventional culturing significantly increases the sensitivity in detection of H. pylori.

Adult↗
PubMed2001

Evaluation of two commercial enzyme immunoassays, testing immunoglobulin G (IgG) and IgA responses, for diagnosis of Helicobacter pylori infection in children.

Serological testing to diagnose Helicobacter pylori infection in children is still controversial, although commonly used in clinical practice. We compared the immunoglobulin G (IgG) and IgA results of two commercially available enzyme immunoassays (EIAs) (Pyloriset IgG and IgA and Enzygnost II IgG and IgA) for 175 children with abdominal symptoms divided into three age groups (0 to < or =6 years, n = 47; >6 to < or =12 years, n = 77; >12 years, n = 51). A child was considered H. pylori infected if at least two of three tests (histology, rapid urease test, 13C-urea breath test) or culture were positive and noninfected if all results were concordantly negative. Of 175 children, 93 (53%) were H. pylori negative and 82 were H. pylori positive. With the recommended cutoff values, the overall specificity was excellent for all four EIAs (95.7 to 97.8%) regardless of age. Sensitivity varied markedly between tests and was 92.7, 70.7, 47.5, and 24.4% for Enzygnost II IgG, Pyloriset IgG, Enzygnost II IgA, and Pyloriset IgA, respectively. Sensitivity was low in the youngest age group (25 to 33.3%), except for Enzygnost II IgG (91.6%). Receiver-operating curve analyses revealed that lower cutoff values would improve the accuracy of all of the tests except Enzygnost II IgG. Measurement of specific IgA, in addition to IgG, antibodies hardly improved the sensitivity. The specificity of commercial serological tests is high in children when the cutoff values obtained from adults are used. In contrast, sensitivity is variable, with a strong age dependence in some, but not all, tests. We speculate that young children may have a different immune response to H. pylori, with preferable responses to certain antigens, as well as lower titers than adults. The Pyloriset test may fail to recognize these specific antibodies.

Adolescent↗
PubMed2001

Rapid and accurate determination of genotypic clarithromycin resistance in cultured Helicobacter pylori by fluorescent in situ hybridization.

Phenotypic susceptibility testing for clarithromycin by E-test and disk diffusion of 109 cultured Helicobacter pylori isolates was compared with the genotypic susceptibility determination by fluorescent in situ hybridization (FISH). No discrepancies were found between these three methods. However, FISH has the advantage of providing results after 3 h.

Anti-Bacterial Agents↗