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Biomedical subjects

S Koletzko

Publications and source records attributed to S Koletzko.

At least 19 recordsLinked to original sources
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↗
PubMed2001

Analysis of the RET, GDNF, EDN3, and EDNRB genes in patients with intestinal neuronal dysplasia and Hirschsprung disease.

BACKGROUND: Hirschsprung disease (HSCR) is a frequent congenital disorder with an incidence of 1 in 5000 live births, characterised by the absence of parasympathetic intramural ganglion cells in the hindgut resulting in intestinal obstruction in neonates and severe constipation in infants and adults. Intestinal neuronal dysplasia (IND) shares clinical features with HSCR but the submucosal parasympathetic plexus is affected. IND has been proposed as one of the most frequent causes of chronic constipation and is often associated with HSCR. METHODS: We examined 29 patients diagnosed with sporadic HSCR, 20 patients with IND, and 12 patients with mixed HSCR/IND for mutations in the coding regions of the RET, GDNF, EDNRB, and EDN3 genes. The entire coding regions were analysed by single strand conformational polymorphism and DNA sequencing. RESULTS: Only three RET mutations were detected in patients with HSCR. In patients with IND or a mixed HSCR/IND phenotype, no mutations in these genes were observed. While HSCR and HSCR/IND showed over representation of a specific RET polymorphism in exon 2, IND exhibited a significantly lower frequency comparable with that of controls. CONCLUSIONS: The mutation frequency found in our sporadic HSCR patients (10%) and the allelic distribution of RET polymorphisms are comparable with earlier published data. A significantly different allelic distribution in an established HSCR associated polymorphism argues against common genetic pathways for HSCR and IND.

Alleles↗
PubMed2000

Influence of age on 13C-urea breath test results in children.

BACKGROUND: The 13C-urea breath test for diagnosis of Helicobacter pylori infection has not been validated in infants and young children. The influence of age on the test results was studied by conventional validation against invasive methods and by mathematical estimation in a large pediatric population. METHODS: The breath test was performed in 1499 children aged 2 months to 18 years. After a fasting period of 4 hours or more, 75 mg 13C-urea was ingested with cold apple juice, breath samples were taken at baseline and at 15 and 30 minutes. The distribution of the natural logarithms of the delta-over baseline (DOB) values were calculated, and the optimal cutoff values between positive and negative test results and gray zones with a risk of misclassification more than 10% were determined for both time points. In a subgroup of 149 children results of the breath test were compared with concordant results of histology and rapid urease test; 53 of them were less than 6 years of age. RESULTS: Logarithmic results of 1499 breath tests revealed two normally distributed subgroups with minimal overlap. The calculated optimal cutoff values were 4.7/1000 at 15 minutes and 5.0/1000 at 30 minutes. At 30 minutes, only 2.6% of all results were in the calculated gray zone (2.6-6.5/1000). Age was negatively correlated to DOB values of both negative (r = -0.223) and positive results (r = -0.291; P < 0.001). Breath test-negative and -positive children 6 or less years of age had significantly higher mean DOB values (P < 0.02) and a larger proportion of results within the gray zone than older children. Compared with biopsy-based results, the least discrepancies occurred at a cutoff of 5.0/1000: 0 of 61 infected (sensitivity 100%) and 6 of 88 noninfected children. Because five of the false-positive results were obtained in children less than 6 years of age, specificity and positive predictive values were lower in this age group than in older patients (88.1% vs. 97.8% and 68.8% vs. 98.0%, respectively). CONCLUSIONS: Under the applied conditions, the 13C-urea breath test shows an excellent separation between positive and negative results. Because of some overlap and a strong age effect, definition of a gray zone appears more meaningful than a threshold value. Because infants and young children have a high risk for false-positive breath test results, the values for cutoff and gray zones may have to be adapted. Further validation studies against invasive methods are warranted in this age group.

Adolescent↗
PubMed2000

Pharmacokinetics of orally administered omeprazole in children. International Pediatric Omeprazole Pharmacokinetic Group.

OBJECTIVES: The aim of this study was to examine the pharmacokinetics of orally administered omeprazole in children. METHODS: Plasma concentrations of omeprazole were measured at steady state over a 6-h period after administration of the drug. Patients were a subset of those in a multicenter study to determine the dose, safety, efficacy, and tolerability of omeprazole in the treatment of erosive reflux esophagitis in children. Children were 1-16 yr of age, with erosive esophagitis and pathological acid reflux on 24 h-intraesophageal pH study. The "healing dose" of omeprazole was that at which subsequent intraesophageal pH study normalized. Children remained on this dose for 3 months, and during this period the pharmacokinetics were measured. RESULTS: A total of 57 children were enrolled in the overall healing phase of the study. Pharmacokinetic study was optional for subjects and was performed in 25 of the 57 enrolled. The doses of omeprazole required were substantially higher doses per kilogram of body weight than in adults. Values of the pharmacokinetic parameters of omeprazole were generally within the ranges previously reported in adults. However, the plasma levels, area under the plasma concentration versus time curve (AUC), plasma half-life (t(1/2)), and maximal plasma concentration (Cmax), were lower in the younger age group, when the AUC and Cmax were normalized to a dose of 1 mg/kg. Furthermore, within the group as a whole, these values showed a gradation from lowest in the children 1-6 yr of age to higher in the older age groups. CONCLUSIONS: The pharmacokinetics of omeprazole in children showed a trend toward higher metabolic capacity with decreasing age, being highest at 1-6 yr of age. This may explain the need for higher doses of omeprazole on a per kilogram basis, not only in children overall compared with adults but, in many cases, particularly in younger children.

Administration, Oral↗
PubMed1999

The role of cisapride in the treatment of pediatric gastroesophageal reflux. The European Society of Paediatric Gastroenterology, Hepatology and Nutrition.

BACKGROUND: Cisapride is a gastrointestinal prokinetic agent that is used worldwide in the treatment of gastrointestinal motility-related disorders in premature infants, full-term infants, and children. Efficacy data suggest that it is the most effective commercially available prokinetic drug. METHODS: Because of recent concerns about safety, a critical and in-depth analysis of all reported adverse events was performed and resulted in the conclusions and recommendations that follow. RESULTS: Cisapride should only be administered to patients in whom the use of prokinetics is justified according to current medical knowledge. If cisapride is given to pediatric patients who can be considered healthy except for their gastrointestinal motility disorder, and the maximum dose does not exceed 0.8 mg/kg per day in 3 to 4 administrations of 0.2 mg/kg (not exceeding 40 mg/d), no special safety procedures regarding potential cardiac adverse events are recommended. However, if cisapride is prescribed for patients who are known to be or are suspected of being at increased risk for drug-associated increases in QTc interval, certain precautions are advisable. Such patients include those:(1) with a previous history of cardiac dysrhythmias, (2) receiving drugs known to inhibit the metabolism of cisapride and/or adversely affect ventricular repolarisation, (3) with immaturity and/or disease causing reduced cytochrome P450 3A4 activity, or (4) with electrolyte disturbances. In such patients, ECG monitoring to quantitate the QTc interval should be used before initiation of therapy and after 3 days of treatment to ascertain whether a cisapride-induced cardiac adverse effect is present. CONCLUSIONS: With rare exceptions, the total daily dose of cisapride should not exceed 0.8 mg/kg divided into 3 or 4 approximately equally spaced doses. If higher doses than this are given, the precautions above are advisable. In any patient in whom a prolonged QTc interval is found, the dose of cisapride should be reduced or the drug discontinued until the ECG normalizes. If the QTc interval returns to normal after withdrawal of cisapride, and the administration of cisapride is considered to be justified because of its efficacy and absence of alternative treatment options, cisapride can be restarted at half dose with control of the QTc interval. Unfortunately, at present, normal ranges of QTc interval in children are unknown. However, a critical analysis of the literature suggests that a duration of less than 450 milliseconds can be considered to be within the normal range and greater than 470 milliseconds as outside it.

Arrhythmias, Cardiac↗
PubMed1999

Rectal biopsy for diagnosis of intestinal neuronal dysplasia in children: a prospective multicentre study on interobserver variation and clinical outcome.

BACKGROUND: Intestinal neuronal dysplasia (IND) of the colonic submucous plexus is considered to be a congenital malformation of the enteric nervous system causing symptoms resembling those of Hirschsprung's disease. In contrast with the established diagnosis of aganglionosis using enzyme histochemistry, controversy exists over the diagnostic criteria of IND on rectal biopsies previously defined by a consensus report and the causal relation between morphological findings and clinical symptoms. AIMS: The interobserver variability was prospectively investigated with respect to final diagnoses and several histological features in rectal biopsy specimens from children suspected of having colonic motility disturbances. METHODS: 377 biopsy specimens from 108 children aged 4 days to 15 years were independently coded without knowledge of clinical symptoms by three experienced pathologists for 20 histological features, and a final diagnosis was given for every case. Interobserver variation for the different items and the final diagnosis were analysed using Cohen's kappa statistic. Clinical data at biopsy and outcome after 12 months were related to morphological findings. RESULTS: The three pathologists agreed completely with respect to the diagnosis Hirschsprung's disease (kappa = 1), but in only 14% of the children without aganglionosis. In 15 (17%) of the 87 children without aganglionosis, at least one pathologist judged the case as normal, while another diagnosed IND. kappa values were close to the zero value expected by chance for the diagnoses normal and IND. Young age was related to the presence of several morphological features-for example, acetylcholine esterase staining and presence of giant ganglia. Children with chronic constipation diagnosed as having IND, given no other specific diagnosis by any of the pathologists, were significantly younger (median 8.8 months) and had a higher cure rate after one year (60%) than constipated patients considered by all observers to have no histological abnormalities (median 6.1 years, cure rate 23%). CONCLUSIONS: In contrast with Hirschsprung's disease, there is a high interobserver variation with regard to the different morphological features and final diagnosis of IND, based on the criteria and conditions of the previous consensus report. The high frequency of histological "abnormalities" in young infants suggests that some of the features may represent a normal variant of postnatal development rather than a pathological process. Investigations using more refined and morphometric methods in rectal specimens from infants and children without bowel disease are needed to define the normal range of morphological appearance at different ages. These preliminary data indicate that, with current knowledge, rectal biopsy for diagnostic purposes should only be performed in constipated children for diagnosis of Hirschsprung's disease.

Adolescent↗
PubMed1999

Atypical CD3+ CD4(low) cell population in a boy with fatal EBV-infection.

A previously healthy 10-year-old Greek boy born to nonconsanguineous healthy parents developed progressive liver disease after acute infectious mononucleosis. EBV-induced autoimmune hepatitis was suspected and treatment was started with high-dose prednisolone, acyclovir and intravenous immunoglobulins. Despite therapy, his liver function continuously deteriorated and the child died 9 months later in profound immune deficiency from candida septicemia. Flow cytometric analysis of his lymphocytes revealed a major subpopulation of atypical cells (20.3%) which were CD3+, fitted into the lymphocyte gate but showed a very low level of CD4 expression, comparable to that of monocytes. After short-time cell culture, the cells became adherent and developed granules and dendrites. We conclude that these cells may represent strongly activated CD4+ T lymphocytes with downregulated CD4 expression or a subtype of dendritic cells.

Autoimmunity↗