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Cystic fibrosis is the most common, life-threatening, autosomal recessive disease in the Caucasian population. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene, which encodes a chloride ion channel expressed on the surface of epithelial cells. There are more than 2000 variants of the cystic fibrosis transmembrane conductance regulator gene reported worldwide. Some of these variants cause classic cystic fibrosis, while others are labeled as variants of unknown significance or variants of varying clinical consequences alleles and associated with atypical disease or cystic fibrosis transmembrane conductance regulator-related disorders. Although these alleles do not directly cause cystic fibrosis, they may predispose compound heterozygous patients to certain clinical phenotypes. Specifically, 1677delTA has been reported as a pathogenic allele in homozygous state or in combination with other cystic fibrosis-causing alleles. However, the L997F allele is considered to be benign or causative of non-classic cystic fibrosis or cystic fibrosis transmembrane conductance regulator-related disorders in combination with other pathogenic alleles. In this case series, we describe three cases with 1677delTA and L997F genotype, and speculate that a co-concurrence of these two alleles in trans does not cause classic cystic fibrosis symptoms; however, because the late-onset of cystic fibrosis is possible in the presence of rare alleles, such as L997F, longer follow-up of these patients and identification of a greater number of adults with 1677delTA/L997F genotype are necessary to make final conclusion about the nature of this genotype.

Background Nephrotic syndrome (NS) is one of the most frequent occurring chronic kidney diseases in childhood, despite its rarely occurrence in the general population. Detailed information about clinical data of NS (e.g. average length of stay, complications) as well as of secondary nephrotic syndrome (SNS) is not well known. Methods A nationwide ESPED follow-up study presenting the clinical course and management of children with NS in Germany. Results In course of 2 years, 347 children developed the first onset of NS, hereof 326 patients (93.9%) had a primary NS, and 19 patients had a SNS (missing data in 2 cases), the majority due to a Henoch-Schönlein Purpura. Patients with steroid-resistant NS (SRNS) stayed significantly longer in hospital than children with steroid-sensitive NS (25.2 vs. 13.3 d, p

Die Grundlage der Krankheitsmanifestationen der zystischen Fibrose (CF) ist die Expression und Funktion des Gens der CF, das fur den cystic fibrosis, transmembrane conductance regulator (CFTR) kodiert und auf dem langen Arm des Chromosoms 7 liegt. Das Genprodukt stellt einen ATP-abhangigen Chloridkanal dar, der in der apikalen Membran von Epithelzellen der exkretorischen Drusen lokalisiert ist. Derzeit sind weltweit mehr als 1300 Mutationen im CF-Gen bekannt (www.genet. sickkids.on.ca/cftr). Beim haufigsten Defekt des CFTR an der Position 508 des Gens durch eine Deletion des Phenyalanins (ΔF508), die homo- oder heterozygot bei mehr als 80% deutschsprachiger Patienten vorkommt, resultiert ein gestorter Chloridtransport in das Lumen, z. B. der submukosen Drusen der Atemwege, der Acini des exokrinen Pankreas, der Schweisdrusen und der Gallenwege. Dadurch kommt es zu einem veranderten Ionentransport in exokrine Sekrete. Die Folge sind Dehydratation intraluminaler Sekrete und Veranderungen in den betroffenen Organen: a) Storung der mukoziliaren Clearance in der Lunge mit Akkumulation von zahem Schleim, der die bakterielle Besiedelung mit Bakterien (Staphylococcus aureus, Pseudomonas aeruginosa) fordert und zur chronischen Lungeninfektion fuhrt; b) Bildung eines chlorid-, bicarbonat- und wasserarmen Sekrets im exokrinen Pankreas mit geringerer Loslichkeit und deshalb erhohter Viskositat der Sekreteiweise im sauren Milieu.

Bei den angeborenen Krankheiten des Dunn- und Dickdarms kommt es postpartal zu schweren Durchfallen meist verbunden mit metabolischer Azidose. Die Durchfalle sind weder den osmotisch noch den sekretorisch hervorgerufenen angeborenen Krankheiten zuzuordnen, sondern gehen in der Regel mit Strukturveranderungen der Dunndarmmukosa einher. Sie erfordern eine Dunndarmbiopsie zu Diagnostik. Auf Grund der pathohistologischen Veranderungen kann dann die Verdachtsdiagnose gestellt und durch entsprechende molekulargenetische Untersuchungen bestatigt werden. Die Therapie der angeborenen Strukturveranderungen des Darms ist schwierig. Oft ist eine jahrelange parenterale Ernahrung notwendig. Manchmal kann nur eine Dunndarmtransplantation oder eine Knochmarktransplantation eine Verbesserung der schweren Durchfalle erreichen.

Der akute Brechdurchfall bei Sauglingen ist eine ernste Krankheit, die durch Erbrechen und Durchfall zu schweren Flussigkeits- und Elektrolytverlusten fuhrt. Diese konnen zum hypovolamischem Schock fuhren. Ausloser sind meist Viren (Rotavirus, Norovirus). Der Flussigkeitsverlust wird klinisch eingeschatzt. Hautfarbe, -temperatur, -turgor, Puls, trockene Schleimhaut im Mund und Augen, Niveau der Fontanelle sowie Rekapillarisierungszeit der Finger ergeben das Ausmas der Exsikkose. 3–8 % Exsikkose erfordert eine orale Rehydratation mit Glukose-Elektrolytlosungen, mehr als 9 % erfordert eine i.v.-Therapie. Nach Zufuhr p.o. von 50 ml/kg KG/4 h erfolgt erneut die Beurteilung der Exsikkose. Nach Erholung wird mit der Realimentation begonnen. Das postenteritische Syndrom/persistierende Diarrho ist eine Komplikation des akuten Brechdurchfalls und beginnt 14 Tage nach Beginn der akuten Gastroenteritis. Bei Persistenz fuhrt er in Schwellenlandern zu einer Verschlechterung der Malnutrition. Er ist haufig letal. Ursache sind meist bakterielle Infektionen, bzw. Mischinfektionen mit Parasiten (Giardia lamblia, Amoben oder Cryptosporidien).

Thirty-six founding members from Europe were present in 1968, when the European Society of Paediatric Gastroenterology (ESGA) had its first meeting in Paris. The aim was to create a forum for presentations and discussions of research activities in paediatric gastroenterology in Europe. At the second meeting of ESGA 1969 in Interlaken, an important landmark was set for all gastroenterologists in the world. In this conference, the first ever criteria for "the Diagnosis of Coeliac Disease" (CD) were established. In 1990, the revised criteria for the diagnosis of CD were published. After the introduction of new noninvasive techniques, like tissue transglutaminase 2-antibodies and the HLADQ2/HLADQ8 determinations in blood, "new" criteria for the diagnosis of CD were published in 2012 by the European society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Close collaboration of ESPGHAN and the North American Society of Paediatric Gastroenterology, Hepatology and Nutrition led to mutual meetings. The first combined meeting was 1978 in Paris, followed by meetings in New York, Amsterdam, Houston, and last in Toulouse. The first World Congress of Paediatric Gastroenterology took place in Boston 2000 followed by congresses in Paris, Iguazu, Taipeh, and Toronto. The creation of specialised committees (Nutrition Committees, GI-Committee, and Hepatology-Committee) enabled the society to elaborate numerous guidelines for standards in the diagnosis and treatment of diseases within the subspecialties. The Journal of Paediatric Gastroenterology and Nutrition, as organ of ESPGHAN and the North American Society of Paediatric Gastroenterology, Hepatology and Nutrition since 1991, serves as the voice for these worldwide accepted guidelines. Growing educational activities with summer schools, the Young Investigator Forum and the creation of working groups have distributed our current knowledge among the younger generation and led to fruitful reports, guidelines, and syllabus. In 1992, ESPGHAN was 1 of the founding 7 members of the United European Gastroenterology Federation (UEGF), which developed into a successful organisation for gastroenterology in Europe. This year we celebrate the 50th anniversary of ESPGHAN at our annual Meeting in Geneva.

The incidence of childhood nephrotic syndrome (NS) in Germany is not well known. An ESPED-based nationwide collection of epidemiological data of children in 2005 and 2006. The mean age of NS at onset was 5.5 ± 3.7 years. The gender ratio of boys to girls was 1.8:1. The average length of stay was 15.5 ± 11.2 days, with younger children remaining significantly longer in hospital. Steroid-resistance was more common in children ≥8 years (p = 0.023). Focal-segmental glomerulosclerosis (FSGS) was more common in children >10 years (p = 0.029). The ratio of males to females with FSGS was 1:1.9, thus the FSGS risk for girls at onset was 3.3-times greater. Considering the available data, the incidence of NS in Germany is 1.2/100,000 in the population

The history of maltose-active disaccharidases is closely related to the history of the sugar and starch industry. It began in the 19th century, when a shortage of cane sugar occurred in continental Europe, because Napoleon Bonaparte decreed that no goods could be imported from England to the countries he occupied. Other sugar sources had to be found, and it led to the identification of sugar beets as alternative source of sugar by Marggraf in 1774, to the detection of starch hydrolysis by diluted sulfuric acid by Kirchhoff in 1812, and to the starch digestion enzyme, α-amylase, by Payen in 1833. In the 20th century, Borkström's group in Sweden investigated the absorption of nutrients in human adults by transintubation techniques and found that the luminal concentration of invertase was small compared to that of α-amylase. They speculated that the major locus of this enzyme activity must be in the intestinal cells. Borkström's coworker, Dahlqvist, investigated the maltose-active enzymes in pig intestine, and a second group around Semenza studied the maltase-active enzymes in rabbit intestine. After the first descriptions of congenital sucrase-isomaltase deficiency in 1960 and 1961, the research on disaccharidases increased. Dahlqvist published the first quantitative method to measure these enzymes. Consecutive research led to the discovery of 4 maltases, which were later identified as 2 complex enzymes: the sucrase-isomaltase complex and the maltase-glucoamylase complex. The homology of the 2 enzyme complexes was later determined when the cDNA sequences of the 2 complexes in human intestine were identified.

ALG3-CDG is one of the very rare types of congenital disorder of glycosylation (CDG) caused by variants in the ER-mannosyltransferase ALG3. Here, we summarize the clinical, biochemical, and genetic data of four new ALG3-CDG patients, who were identified by a type I pattern of serum transferrin and the accumulation of Man5 GlcNAc2 -PP-dolichol in LLO analysis. Additional clinical symptoms observed in our patients comprise sensorineural hearing loss, right-descending aorta, obstructive cardiomyopathy, macroglossia, and muscular hypertonia. We add four new biochemically confirmed variants to the list of ALG3-CDG inducing variants: c.350G>C (p.R117P), c.1263G>A (p.W421*), c.1037A>G (p.N346S), and the intron variant c.296+4A>G. Furthermore, in Patient 1 an additional open-reading frame of 141 bp (AAGRP) in the coding region of ALG3 was identified. Additionally, we show that control cells synthesize, to a minor degree, a hybrid protein composed of the polypeptide AAGRP and ALG3 (AAGRP-ALG3), while in Patient 1 expression of this hybrid protein is significantly increased due to the homozygous variant c.160_196del (g.165C>T). By reviewing the literature and combining our findings with previously published data, we further expand the knowledge of this rare glycosylation defect.

K. Brockmann*, H. G. Schlack, R. Blank, M. A. Landoldt, F. H. Sennhauser, H. von Voss und R. Schmid Klinik f€ur Kinderheilkunde und Jugendmedizin, Universitatsmedizin Gottingen, Gottingen, Deutschland Bonn, Deutschland Klinik f€ur Kinderneurologie und Sozialpadiatrie, Kinderzentrum Maulbronn gGmbH, Maulbronn, Deutschland Abt. f€ur Psychosomatik und Psychiatrie, Kinderspital Z€urich, Z€urich, Schweiz Universitatskinderklinik Z€urich, Z€urich, Schweiz Privatinstitut f€ur Soziale Padiatrie im Zentrum f€ur Humangenetik und Laboratoriumsmedizin, Martinsried-Planegg, Deutschland Kindernetzwerk e. V, Aschaffenburg, Deutschland

Performing well-designed and ethical trials in pediatric inflammatory bowel diseases (IBD) is a priority to support optimal therapy and reduce the unacceptable long lag between adult and pediatric drug approval. Recently, clinical trials in children have been incorporating placebo arms into their protocols under conditions that created controversy. Therefore, 4 organizations (the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition; European Crohn's and Colitis Organization; the Canadian Children IBD Network; and the Global Pediatric IBD Network) jointly provide a statement on the role of placebo in pediatric IBD trials. Consensus was achieved by 94 of 100 (94%) voting committees' members that placebo should only be used if there is genuine equipoise between the active treatment and placebo; for example, this may be considered in trials of drugs with new mechanisms of action without existing adult data, especially when proven effective alternatives do not exist outside the trial. Placebo may also be used in situations where it is an add-on to an effective therapy or to evaluate exit-strategies of maintenance therapy after long-term deep remission. It has been, however, agreed that no child enrolled in a trial should receive a known inferior treatment both within and outside the trial. This also includes withholding therapy in children who show clinical response after a short induction therapy. Given the similarity between pediatric and adult IBD regarding pathophysiology and response to treatments, drugs generally cannot be considered being in genuine equipoise with placebo if it has proven efficacy in adults. Continued collaboration of all stakeholders is needed to facilitate drug development and evaluation in pediatric IBD.

Long-term outcomes of children with nephrotic syndrome have not been well described in the literature. Cross-sectional study data analysis of n = 43 patients with steroid-sensitive (SSNS) and n = 7 patients with steroid-resistant (SRNS) nephrotic syndrome were retrospectively collected; patients were clinically examined at a follow-up visit (FUV), on average 30 years after onset, there was the longest follow-up period to date. The mean age at FUV was 33.6 years (14.4–50.8 years, n = 41). The mean age of patients with SSNS at onset was 4.7 years (median 3.8 years (1.2–14.5 years), the mean number of relapses was 5.8 (0 to 29 relapses). Seven patients (16.3%) had no relapses. Eleven patients were “frequent relapsers” (25.6%) and four patients still had relapses beyond the age of 18 years. Except of cataracts and arterial hypertension, there were no negative long-term outcomes and only one patient was using immunosuppressant therapy at FUV. 55% of patients suffered from allergies and 47.5% had hypercholesterolemia. Two patients suffered a heart attack in adulthood. A younger age at onset (

Since the conception of an idea of a few paediatric gastroenterologists in Europe to create a society for Paediatric Gastroenterology in 1967, and its foundation in 1968, half a century has passed. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) now celebrates its 50th anniversary and its utmost success in combining clinical and scientific expertise in the fields of paediatric gastroenterology, haepatology, and nutrition. To describe this success story 14 of the still living presidents of ESPGHAN recount their impressions of the steady growth of ESPGHAN with all the historical facets from their own points of view. This historical view of ESPGHAN over the last 5 decades provides personal accounts of the development of all activities and creations of this great European Society. The Society started as a small family of experts in the field into a global working open society involved in a large variety of activities within the subspecialties, becoming a leading organisation in Europe and beyond. This unique view gives also a wonderful insight into the famous clinicians and researchers from all over Europe who have helped in the growth and development of ESPGHAN. By describing all these activities and collaborations it becomes clear that this astonishing pan-European enterprise was achieved by people who put considerable effort and time into the development of this society. Their statements serve as a historical source and reference for future evaluation of the first 50 years of ESPGHAN. In depicting different time episodes, and by assembling all the historical pieces of a puzzle together, the statements help to illustrate how a highly structured society such as ESPGHAN has evolved over the last 50 years, for what it stands for today and what is to be expected in the future.

The majority of the studies in the field of childhood asthma lie within the scope of allergy/atopic asthma; however, airway hyperresponsiveness is considered a marker of asthma, independent of the atopic status and should be regarded as a parallel pathological process that can lead to subsequent symptoms and clinical evidence of asthma in children, without the evidence of atopy. The aim of this study is to estimate the possible differences in clinical and lung functions, and the immunological status of children with atopic and nonatopic asthma phenotypes. In a prospective study design, 54 children (age 3-18 years) in Germany were monitored via active surveillance, by twice-a-week phone calls. All the children were divided into two groups, based on their atopic status, clinical date and lung function tests. The first 27 patients had atopic asthma (AA), whereas the second set of 27 patients had nonatopic asthma (NA). All patients underwent IgE and RAST tests for the most common inhalant allergens, and a quantitative measurement of Eosinophil Cationic Protein (ECP) by CAP-radioallergosorbent test-fluorescence enzyme immunoassay (UniCAP, Pharmacia Diagnostics, Germany). Further, the IgA, IgM, IgG subclasses, IL-6 and CRP levels in the serum were tested. The resultant data showed significant differences in the prevailing IgE level 317.5±58 g/l in AA versus 83±21 in NA. However, there was no significant distinction either in the ECP serum level in children with atopic and nonatopic asthma or in the IL-6 serum level. An unexpected result was the significant drop in the level of serum CRP in group NA – 0.68±0.37 g/l; while in group AA this result was 1.5±0.38 g/l. No significant differences were noted between the mean values of the IgM and IgG levels in patients of all groups; however, the IgG levels increased only in the children with nonatopic asthma. Our study did not reveal any type of immunoglobulin deficiency. The IgA level was relatively decreased in children with nonatopic asthma compared with those with the atopic form. Patients from group NA had significantly higher IgG4 subclass levels than patients from group AA. The results of our study show that both atopic and nonatopic asthma are diseases, with similar inflammatory changes, however having probably different pathogenetic immunological mechanisms.

Chemotherapy regimes in children with cancer often cause gastrointestinal side effects. Only limited data exist on the use of endoscopy in this group of patients.Retrospective review over a time period of 8.5 years identified 57 endoscopies (49 upper endoscopies, four colonoscopies, three sigmoidoscopies, one rectoscopy) in 38 patients (mean age 12.8 years). Seventeen children (45%) had hematological malignancies and 21 (55%) had solid tumors. In 12 children, platelet count was50 × 10(9)/L and 10 children were neutropenic (ANC1 × 10(9)/L; absolute neutrophil count).Forty diagnostic endoscopies, seven follow-up endoscopies, and 10 therapeutic endoscopies were performed. Biopsies were taken in 30 (75%) of 40 diagnostic endoscopies and microbiology samples in 17 (42.5%). Pathological findings identified in 33 (82.5%) diagnostic endoscopies: esophagitis 15 (37.5%)-two of them infections: 1 candida, 1 HSV (herpes simplex virus); Mallory-Weiss tears 5 (12.5%); gastritis 18 (45%; four Helicobacter pylori positive); ulcer 1 (2.5%); duodenitis 11 (27.5%); neoplasia 3 (7.5%); and colitis 5 (12.5%). Therapeutic endoscopies: Four PEG (percutaneous endoscopic gastrostomy) tube placements, one tube removal, two sclerotherapies for esophageal varices, three nasojejunal tubes for enteral nutrition (EN), and three additional tubes in primary diagnostic endoscopies.One episode of fever (38.5°C) after colonoscopy, one localized infection after PEG tube placement, and two episodes of temporary desaturation. No association of neutropenia with more infections was observed. No bleeding in thrombocytopenic patients was observed.The data show that endoscopy in high-risk pediatric patients with malignant diseases is a safe procedure. Endoscopy reveals relevant information and have therapeutic impact with high probability. Tube placement techniques can help to maintain EN.

In den letzten Jahren brachten verschiedene Hersteller Milchgetranke fur Kleinkinder unter Bezeichnungen wie Kindermilch, Kleinkindmilch, Juniormilch oder im englischen Sprachraum „milk for kids“, „growing-up milk“ (GUM) oder „toddler milk“ auf den Markt, die aufgrund ihrer Zusammensetzung als vorteilhaft gegenuber Kuhmilch beworben werden. Die Ernahrungskommission der Deutschen Gesellschaft fur Kinder- und Jugendmedizin (DGKJ) stellt, wie bereits im Jahr 2001, fest, dass spezielle Milchgetranke einschlieslich Folgemilch fur die Ernahrung von Kleinkindern grundsatzlich nicht notwendig sind. Wenn jedoch Trinkmilch durch Kleinkindermilch ersetzt wird, sollten sich die Produkte in Bezug auf Kalzium-, Vitamin-A- und -B2-Gehalt an Vollmilch und in Bezug auf den Energiegehalt an teilentrahmter Kuhmilch orientieren. Wunschenswert ist, dass sie sich in Bezug auf den Jod- und Vitamin-D-Gehalt an den Vorgaben der Folgenahrung orientieren. Aromastoffe und Susungsmittel sollten moglichst vermieden werden. Die Produkte sollen aus Tasse oder Becher und nicht aus einer Saugflasche getrunken werden.

Recent observations indicate that human milk oligosaccharides (HMO) are involved in a variety of physiological processes in infants. Their metabolic fate, however, is virtually unknown. We investigated metabolic aspects in infants after endogenous13C-labelling of HMO. An oral bolus of natural and13C-labelled galactose (Gal; 23 g Gal+4 g13C-Gal) was given to ten lactating women. Aliquots of milk at each nursing as well as breath samples from the mothers and urine from their infants were collected over 36 h. The13C-enrichment of HMO and their renal excretion was determined by isotope ratio-MS; characterisation was achieved by fast atom bombardment-MS. After the Gal bolus was given, an immediate13C-enrichment in milk and in infants' urine was observed which lasted 36 h. Mass spectrometric analysis of13C-enriched urinary fractions confirmed the excretion of a variety of neutral and acidic HMO without metabolic modification of their structures. Components with glucose split off at the reducing end were also detectable. Quantitative data regarding the infants' intake of lacto-N-tetraose and its monofucosylated derivative lacto-N-fucopentaose II ranged from 50 to 160 mg with each suckling, respectively; renal excretion of both components varied between 1 and 3 mg/d. Since the intake of individual HMO by the infants was in the range of several hundred mg per suckling, i.e. several g/d, and some of these components were excreted in mg amounts as intact HMO with the infants' urine, not only local but also systemic effects might be expected.

Objectives: To determine the pediatric reference interval for serum β-trace protein (β-TP) and to compare β-TP with established LMW markers of GFR, i.e., cystatin C (CysC) and β 2 -microglobulin (β 2 -M). Design and methods: All three LMW markers were measured immunonephelometrically. In 106 children above the age of 2 years without evidence of kidney disease, non-parametric reference intervals were calculated. The relative rise of the GFR marker concentrations above the upper reference was studied in 107 samples from 96 patients covering the entire GFR range. Results: Above 2 years, the reference range of β-TP was constant at 0.43–1.04 mg/L. With decreasing Schwartz-GFR, there was a comparable rise in β-TP and β 2 -M, while CysC rose less in the group with GFR below 30 mL/min/1.73 m 2 (278 ± 49% [CysC] versus 336 ± 65% [β-TP] and 342 ± 76% [β 2 -M]; p = 0.043 and 0.027, respectively). Conclusions: These data confirm the potential of s-TP as an endogenous GFR marker in children.

A single-nucleotide variant, C/T(-13910), located 14 kb upstream of the lactase gene (LCT), has been shown to be completely correlated with lactase persistence (LP) in northern Europeans. Here, we analyzed the background of the alleles carrying the critical variant in 1,611 DNA samples from 37 populations. Our data show that the T(-13910) variant is found on two different, highly divergent haplotype backgrounds in the global populations. The first is the most common LP haplotype (LP H98) present in all populations analyzed, whereas the others (LP H8-H12), which originate from the same ancestral allelic haplotype, are found in geographically restricted populations living west of the Urals and north of the Caucasus. The global distribution pattern of LP T(-13910) H98 supports the Caucasian origin of this allele. Age estimates based on different mathematical models show that the common LP T(-13910) H98 allele (approximately 5,000-12,000 years old) is relatively older than the other geographically restricted LP alleles (approximately 1,400-3,000 years old). Our data about global allelic haplotypes of the lactose-tolerance variant imply that the T(-13910) allele has been independently introduced more than once and that there is a still-ongoing process of convergent evolution of the LP alleles in humans.

Background Human Bocavirus (HBoV), a new species of the genus parvovirus newly detected in 2005, seems to be a worldwide distributed pathogen among children with respiratory tract infection (prevalence 2%–18%). Recently published retrospective studies and one prospective birth cohort study suggest that HBoV-primary infection occurs in infants. Methods Prospective single center study over one winter season (November 2005–May 2006) with hospitalized children without age restriction using PCR-based diagnostic methods. Results HBoV DNA was detected in 11 (2.8%) of 389 nasopharyngeal aspirates from symptomatic hospitalized children (median age 9.0 months; range: 3–17 months). RSV, HMPV, HCoV, and Influenza B were detected in 13.9% ( n = 54), 5.1% ( n = 20), 2.6% ( n = 10), and 1.8% ( n = 7), respectively. There was no influenza A DNA detected in any of the specimens. The clinical diagnoses were acute wheezing (bronchitis) in four patients, radiologically confirmed pneumonia in six patients (55%) and croup syndrome in one patient. In five to six patients with pneumonia, HBoV was the only pathogen detected. While no patient had to be mechanically ventilated, 73% needed oxygen supplementation. In four (36.4%) patients at least one other viral pathogen was found (plus RSV n = 3; 27.3%; Norovirus n = 1; 9.1%). Conclusion HBoV causes severe respiratory tract infections in infants and young children. Its role as a copathogen and many other open questions has to be defined in further prospective studies.

The human Metapneumovirus (HMPV) has been discovered by von den Hoogen et al. in 2001 and seems to play an important role as etiologic agent in childhood respiratory tract infections in particular involving infants after the 6th month of life and toddlers. Duly considering the hitherto published studies and retrospective analysis of two HMPV seasons (2002-2004) at our institution this review focuses on children, who had to be hospitalized due to HMPV infection. The analysis confirmed, that among those patients there is a high proportion of children with pre-existing risk factors for a complicated clinical course, a high proportion of children with bronchiolitis or pneumonia and a relevant proportion of children with HMPV related apnoeas, most prevalent in the prematurely born. Although the first HMPV infection takes place somewhat later in infancy, the data do not show that HMPV infection is in general milder than RSV infection in hospitalized children. Clinical symptoms and radiological signs do not permit tentative conclusions on the causative agent. This underlines the necessity of specific diagnostic efforts (in case of HMPV with PCR). HMPV may cause lobar or segmental pneumonias difficult to distinguish from bacterial lower respiratory tract infection. Children admitted to the hospital with an acute exacerbation of asthma bronchiale or cystic fibrosis should not only be tested for RSV but also for HMPV. Prospective studies investigating specific therapeutic interventions or describing the impact and prevention of nosocomial HMPV in fection are awaited for. There has been one report of a meningoencephalitis possibly related to HMPV. Thus, liquor samples in such cases should be tested for HMPV too.

In this short report we discuss the temporal association between an acute life threatening event (ALTE) and a RT‐PCR confirmed coronavirus HCoV‐229E infection in a 4 months old otherwise healthy infant. More detailed microbiological investigations of affected children even without apparent signs of a respiratory tract infection may help to clarify the etiology in some patients and extend our understanding of the pathogenesis. PCR‐based techniques should be utilized to increase the sensitivity of detection for old and new respiratory viral pathogens in comparable cases. Pediatr Pulmonol. 2007; 42:393–396. © 2007 Wiley‐Liss, Inc.

Background. Optimal management of pediatric patients with inflammatory bowel disease (IBD) requires early diagnosis. Aim of the study is to compare fecal lactoferrin (FL) as biomarker of intestinal inflammation to CRP in pediatric patients with new-onset IBD.Methods. FL was measured by ELISA in stool specimens collected prior to endoscopy for IBD (IBD-SCAN; TechLab, Blacksburg; normal < 7.3 µg/g feces). CRP was detected in serum (normal < 5 mg/L). Three patient groups were determined:n=21(mean age 13.2) with Crohn’s disease (CD),n=15(mean age 10.9) with ulcerative colitis (UC), andn=20(mean age 11.9) in whom IBD was ruled out. In CD patients the endoscopic severity score SES-CD was correlated with the FL levels.Results.(Mean ± SEM). CRP levels were 27.18 ± 4.2 for CD-cases, 20.8 ± 9.5 for UC, and 0.24 ± 0.06 for non-IBD patients. FL levels were 313.6 ± 46.4 in CD, 370.7 ± 46.9 in UC, and 1.3 ± 0.5 in non-IBD patients. Sensitivity of CRP to detect IBD was 75% with specificity of 100%, positive predictive value of 100%, and negative predictive value of 69%. Sensitivity of FL was 100% with specificity of 95%, positive predictive value of 97.3%, and negative predictive value of 100%. In CD, FL levels correlated positively (R2=0.42) with disease severity as judged by the SES-CD.Conclusions. Elevated FL corresponds to intestinal inflammation, even in patients with normal CRP. With high probability, normal FL excludes intestinal inflammation.

Background & Aims: Few data exist on the molecular events causing intestinal epithelial destruction during inflammatory processes, such as inflammatory bowel disease (IBD). In this work, we analyzed the potential implication of tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) in these inflammatory lesions. Methods: TRAIL and TRAIL-receptor expression were analyzed in normal, inflammatory ileum/colon and human intestinal epithelial cell (IEC) lines (HIEC), Caco-2, and HT-29 using RNase protection assay, real-time and reverse-transcription polymerase chain reaction (RT-PCR), immunohistochemistry, and Western blot analysis. TRAIL-induced activation of NF-κB was determined by electrophoretic mobility shift assay. Caspase-recruitment domain (CARD)15 expression and interleukin-(IL)8 production were studied by RT-PCR and enzyme-linked immunosorbent assay. Apoptosis was monitored using Annexin-V/caspase-3 assays. Results: Normal mature IEC expressed low TRAIL levels, whereas, in inflammatory lesions, TRAIL messenger RNA and protein were markedly up-regulated in IEC and lamina propria lymphocytes at levels comparable with trinitrobenzene sulfonic acid-induced colitis. Interferon-γ and TNF-α potently induced TRAIL in IEC. In vitro analyses revealed a dual biologic effect of TRAIL on HIEC: Under noninflammatory conditions, TRAIL up-regulated via nuclear factor-κB CARD15 and IL-8, whereas, under inflammatory conditions, TRAIL became a potent inducer of apoptosis in HIEC, which was confirmed ex vivo using ileal organ cultures. TNF-α markedly increased the expression of the proapoptotic receptor TRAIL-R2. TRAIL-induced IEC apoptosis required a functional caspase cascade. Conclusions: TRAIL is a new inflammatory mediator implicated in the homeostasis of intestinal epithelial barrier functions. TRAIL is highly up-regulated in IEC in inflammatory ileum and colon. It may augment in an auto-/paracrine fashion the elimination of IEC via apoptosis.

The severity of lung disease in cystic fibrosis may be related to the genetic propensity of the host to produce tumor necrosis fector alpha (TNF-alpha). A polymorphism in the promoter region of the TNF-alpha gene at nucleotide 308 relative to the transcription start site may be important in determing the host's TNF-alpha response. The aim of this study was to assess the correlation between a TNF-308 promoter polymorphism, ex vivo TNF-alpha production (before and after lipopolysaccharide (LPS) stimulation), and clinical status [FEV1, weight (z-score), BMI, Shwachman score, incidence of diabetes mellitus, and Pseudomonas aeruginosa infection). Genotyping for the biallelic TNF-308 polymorphism was performed by using a real-time PCR cycler. Patients (homozygous for Delta F 508) were grouped according to genotype (TNF2 carriers, n = 16, median age = 15 yr, female/male = 5/11; TNF1 homozygotes, n = 37, median age = 21 yr, female/male = 18/19). TNF-alpha was measured using a chemiluminescent immunometric assay. There was a trend toward higher TNF-alpha values [median TNF2 carriers vs. TNF1 homozygotes: x = 56 vs. 43.5 pg/ml, n.s. (Mann-Whitney U-test] in those carrying the polymorphism and better lung function results [FEV(1) (%) 81 vs. 65, n.s.]. These differences equalized [TNF2 carriers vs. TNF1 56 vs. 51 pg/ml, n.s.; FEV1 (%) 84 vs. 79, n.s.] after age adjustment (+/- 2 yr, n = 15, median age TNF2 vs. TNF1-17/18 yr). There were no significant differences for TNF values after LPS stimulation and the incidence of diabetes mellitus. The TNF-308 promoter polymorphism does not seem to influence TNF-alpha release in whole blood cells and clinical status.

The protein-loosing enteropathy (PLE) may result from a broad variety of underlying diseases. These conditions are of systemic nature or locally affecting the gastrointestinal tract. Major symptoms are oedema due to low plasma protein levels. Gastrointestinal symptoms are not necessarily present. The diagnosis is confirmed by the finding of increased faecal concentrations of Alpha-1-Antitrypsin (> 320 mg/L). In the majority of cases, in which underlying diseases are present, the etiology is obvious. In unclear cases the differentiation into inflammatory or circulatory disturbances or alterations of the architecture of the basal membrane is helpful. An economic, staged approach is presented. To localize the site of protein loss imaging is required (abdominal ultrasound, CT-scan, endoscopy and Technetium-Scan). If a circumscribed intestinal source of protein loss is suspected which may be amenable to surgery, intraoperative enteroscopy should be considered. If causal treatment is impossible; intravenous replacement of albumin and immunoglobulines in intervals from 1 to 4 weeks will be necessary. The prognosis in patients with isolated PLE is good. Otherwise it depends on the underlying disease.

Background: Lamina propria T lymphocytes (LPL) of the intestinal mucosa are chronically activated in Crohn’s disease (CD). Defective apoptosis of activated LPL was proposed as a key pathogenic mechanism. In fact, increased expression of antiapoptotic molecules was observed in CD LPL. In the present work, we aimed to analyse the effects and underlying molecular mechanisms of 5-amino salicylic acid (5-ASA) and derivatives on apoptosis of LPL and peripheral blood lymphocytes (PBL) in patients with CD compared with ulcerative colitis (UC) and in non-inflammatory controls. Methods: PBL and LPL were isolated by Ficoll-Hypopaque gradient centrifugation and the EGTA-collagenase method, respectively. PBL/LPL were stimulated with FasL, 5-ASA, sulphapyridine, and sulphasalazine for 24/48 hours and apoptosis was quantified by flow cytometry (annexin V- propidium iodide method) and immunofluorescence. The molecular mechanisms of drug induced apoptosis were analysed in wild-type and FADD−/− Jurkat T cells using western blots and caspase assays. Results: While PBL displayed a normal apoptosis pattern after Fas stimulation in patients with active CD, LPL from inflammatory areas were highly resistant. Comparable resistance to apoptosis was observed in LPL of UC patients. In contrast with 5-ASA, which did not induce apoptosis in lymphocytes, sulphasalazine proved to be a potent proapoptotic agent. Sulphasalazine induced T lymphocyte apoptosis was independent of the Fas pathway but associated with marked downregulation of antiapoptotic bcl-xl and bcl2, activation of the mitochondrial apoptosis signalling pathway, and subsequent activation of caspase-9 and caspase-3. Conclusion: The beneficial effect of sulphasalazine in treating inflammatory bowel disease is at least in part attributable to its proapoptotic effects on LPL which allows potent downregulation of lymphocyte activation.