OBJECTIVES:To perform a prospective, blinded, randomized interventional trial in patients with recurrent abdominal pain. The primary endpoint was to determine the abdominal pain intensity after 2 weeks of fructose restricted diet. Secondary endpoints were changes of pain frequency and a secondary symptom score (SSS).METHODS:103 individuals with recurrent abdominal pain for more than 3 months were randomized. 51 patients were allocated to group A (diet) and 52 to group B (no diet). 2 weeks later the patients underwent hydrogen breath test and were assigned to the test positive or negative group to identify patients with fructose malabsorption.RESULTS:2 weeks after intervention the pain score decreased significantly from a median 5.5 in group A to 4 and did not change significantly in group B (5.3 to 5). In group A both patients with positive and negative breath tests had a significant lower pain score (-2 and -1.75, respectively). Frequency of abdominal pain decreased in both groups but without significant difference, SSS improved only in group A from median 6 to 3.5. Positive breath test was no predicting factor, neither was abdominal pain during the test.CONCLUSIONS:Fructose restricted diet in children and adolescents with recurrent abdominal pain may be of benefit to improve both abdominal pain symptoms and other secondary symptoms. Since a negative breath test result does not exclude a positive response to fructose restriction, the hydrogen breath test does not seem to be the appropriate diagnostic mean to predict the response to the diet.

Objective: The objective of this study was to analyze the effect of a fructose-restricted diet in otherwise healthy children with abdominal pain and pathologic fructose hydrogen breath test.Subjects and methods: 75 children (aging 314 years) with recurrent abdominal pain without gastrointestinal disease and fructose malabsorption followed a fructose restricted diet for 4 weeks.Results: A median decline of weekly pain frequency from 4 (mean 3.64+1.6) before diet to 1 (mean 1.46+1.4; p<0.001) under fructose restriction was documented. The intensity of pain decreased from median 6 (mean 5.83+2.0) before intervention to median 3 (mean 3.4+2.5; p<0001) with diet. Several additional life quality-influencing parameters such as daily stool frequency, nausea, problems to fall asleep, missed school days also improved significantly.Conclusions: Our study provides evidence that dietary fructose restriction represents a useful approach to address recurrent abdominal symptoms in children with fructose malabsorption.

Ein Ikterus ist ein in der Pädiatrie häufiges Symptom, das durch die Einlagerung von Bilirubin in Haut, Schleimhäute und Skleren entsteht. Differenzialdiagnostisch kommt eine Vielzahl von Faktoren in Betracht. Entscheidend ist, im ersten diagnostischen Schritt zwischen konjugierter und unkonjugierter Hyperbilirubinämie zu unterscheiden. Bei Letzterer, dem Leitsymptom der Hämolyse, konzentriert sich die weitere diagnostische Abklärung auf Untersuchungen von Erythrozyten, v. a. Hämoglobinelektrophorese, Blutausstrich und Antikörpertests. Eine unkonjugierte Hyperbilirubinämie ohne erhöhte Hämolyseparameter deutet auf eine Störung der Bilirubinkonjugation hin. Einer konjugierten Hyperbilirubinämie liegt fast immer eine Lebererkrankung zugrunde. Mittels Cholestaseparametern lassen sich intra- und posthepatische Schädigungen unterscheiden. Intrahepatische Ursachen sind virale oder Autoimmunhepatitiden oder metabolische Erkrankungen wie ein M. Wilson. Einem posthepatischen Ikterus liegt meist eine komplette bzw. teilweise obstruktive Cholestase zugrunde. Entscheidend ist, Erkrankungen, die einer umgehenden Behandlung bedürfen, zügig zu erkennen.

Hintergrund: Die chronische Hepatitis C-Virus (HCV)-Infektion stellt ein auch für die Pädiatrie relevantes schwerwiegendes medizinisches Problem dar. Im Verlauf kommt es häufig zu progessiver Lebererkrankung, Zirrhose und hepatozellulärem Karzinom. Wegen der aktuell begrenzten antiviralen Behandlungsmöglichkeiten liegt die Hoffnung unter anderem in der Entwicklung immunmodulatorischer Therapiekonzepte. Ziel dieser Studie war es, mittels eines neuartigen Immunisierungsansatzes durch direkte Beimpfung Dendritischer Zellen (DC) in vivo eine anhaltende zelluläre Immunreaktion gegen ein HCV-Antigen zu erzeugen. Durch intravenöse Injektion von mit HCV-NS5-Protein beladenen Mikropartikeln sollte eine überwiegende Aufnahme des Antigens durch DC erreicht werden. Methoden: Vor der Immunisierung wurde die DC-Population der zu immunisierenden Mäuse vom Stamm BALB/c (H-2d) angereichert. Dazu wurde mittels hydrodynamischer Injektion das den humanen Fms-like-Tyrosinkinase-Rezeptor-3-Liganden (hFlt3L) exprimierende Plasmid (pUMVC3-hFLex) appliziert. Anschließend wurden diesen Tieren zweifach im Abstand von zwei Wochen 100µg Mikropartikel intravenös injiziert, die mit HCV-NS5-Protein beladen waren. Zelluläre Immunreaktionen wurden hinsichtlich der Sekretion von INF-g und IL-2 durch CD4+Zellen untersucht; CD8+T-Zell-Aktivität wurde in vitro mittels CTL-Assay und in vivo anhand der Hemmung von Tumorzellwachstum untersucht. Ergebnisse: Durch die Vorbehandlung mit Flt3L wurde die DC-Population in der Milz auf 43% gesteigert. Diese Zellen wiesen eine deutliche Hochregulation der co-stimulierenden Oberflächenmoleküle CD86, CD80 und CD40 auf. Dies resultierte in einer Antigen-spezifischen Sekretion von TH1-Zytokinen durch Splenozyten. Des Weiteren wurde eine zytotoxische T-Zell-Aktivität gegen NS5-exprimierende Myeloma-Zellen beobachtet. Darüber hinaus war das Wachstum von Tumoren, die von diesen Zellen ausgingen in immunisierten Tieren gehemmt, was die robuste NS5-spezifische CTL-Aktivität auch in vivo unterstreicht. Diskussion: Mit dem hier vorgestellten Ansatz zeigen wir eine effektive Vakzinierungsstrategie gegen ein HCV-Protein. Es gelingt hiermit, eine der bei natürlicher HCV-Infektion ähnlichen Immunreaktion auszulösen: nämlich die Induktion einer starken CD8+CTL-Immunreaktion, die von einer anhaltenden CD4+T-Zell-Aktivität begleitet wird. DC-basierte Immunisierungen sind mittlerweile in klinischer Anwendung. Die Fähigkeit einer Antigen-spezifischen Aktivierung von DC in vivo macht diese Methode zu einer möglichen therapeutischen Strategie bei chronischer HCV-Infektion.

Background: Necrotising enterocolitis (NEC) is the most common gastrointestinal emergency in neonates with high mortality and morbidity especially in very low birth weight infants (VLBW).

Chronic hepatitis C (HCV) infection is a substantial medical problem that leads to progressive liver disease, cirrhosis, and hepatocellular carcinoma (HCC). The aim of this study was to achieve sustained cellular immune responses in vivo to a HCV nonstructural protein using dendritic cell (DC)-based immunization approach. We targeted the HCV NS5 protein to DCs in vivo by injecting microparticles loaded with this antigen. The DC population was expanded in BALB/C mice (H-2(d) ) by hydrodynamic injection of a plasmid pUMVC3-hFLex expressing the secreted portion of the human Fms-like tyrosine kinase receptor-3 ligand (hFlt3). Mice were subsequently injected with microparticles coated with HCV NS5 protein via the tail vein. Cellular immune responses were determined with respect to secretion of INFγ and IL2 by CD4(+) cells and cytotoxic T-lymphocyte (CTL) assays in vitro; inhibition of tumour cell growth was employed for the assessment of CD8(+) generated activity in vivo. We found that Flt3L treatment expanded the DC population in the spleen to 43%, and such cells displayed a striking upregulation of CD86 as well as CD80 and CD40 co-stimulating molecules. Viral antigen-specific T(H) 1 cytokine secretion by splenocytes was generated, and CTL activity against syngeneic NS5 expressing myeloma target cells was observed. In addition, these cells inhibited tumour growth indicating that NS5-specific robust CTL activity was operative in vivo. Thus, the capability of activating DCs in vivo using the methods described is valuable as a therapeutic vaccine strategy for chronic HCV infection.

Background and aim: Hepatitis C infection is a global health problem affecting about 3% of the world's population. However, very little data exists on the prevalence of hepatitis C virus infection in childhood.Methods: We performed a cross-sectional study in 2000 children and adolescents who were treated as in- or out patients in our hospital. Blood samples were collected between February 2002 and June 2004 and were tested for HCV antibodies (anti-HCV). Positive samples were further investigated by HCV specific PCR and Western blot assay.Results: Mean age of children was 8.1 years. 908 (45%) were female and 1092 (55%) mate. One thousand eight hundred and ninety-eight were Caucasian, 37 African, and 65 Asian. 16 (0.8%) tested positive for anti-HCV. HCV-RNA was detectable in one child (0.05%), and three were positive in the Western blot assay (0.15%). The HCV viremic child had received multiple blood transfusions after cardiac surgery. She was asymptomatic with normal transaminases. Seroprevalence of HCV antibodies were equally distributed among boys and girls.Conclusions: The prevalence of persistent hepatitis C in children from an urban hospital in Germany is low. Most patients with HCV antibodies are not infected. Therefore, although universal screening is not warranted, it should always be performed in risk groups such as transfused children because HCV infection in childhood is usually asymptomatic. (C) 2005 The British Infection Society. Published by Elsevier Ltd. All rights reserved.

It is well established that during lamivudine treatment, mutations emerge within the polymerase gene but there is little information about the selection of other mutations in the whole hepatitis B virus (HBV) genome. The aim of this study was to investigate whether mutations outside this region are selected during lamivudine treatment. The complete HBV genomes of six HBsAg positive chronically infected children were isolated from the children's sera before, at the beginning and during lamivudine treatment, amplified and sequenced directly. A change in the mutation rate and type in periods with and without treatment for one and the same patient were examined longitudinally because blood samples were taken long before treatment started. During the testing period before treatment, 12 mutations occurred within 11.7 +/- 8.1 months in all genomes, resulting in a mutation rate of 1.1 x 10(-3) substitutions per site per year. During treatment with lamivudine, 20 mutations occurred in all patients within an average period of 7.6 +/- 1.2 months, giving an average mutation rate of 1.8 x 10(-3) substitutions per site per year. The 20 mutations observed during the treatment period occurred in only 4 of the patients and only 3 patients experienced nonsense mutations during lamivudine treatment. The mutations were spread across the entire genome with a non-significant cluster during treatment in the P-ORF (18 mutations vs. 7, P=0.073) and S-ORF (11 vs. 2, P=0.063). Mutations causing drug resistance did not emerge. This study describes the changes in the complete HBV genome in the spontaneous course of infection and during lamivudine treatment. An increased mutation rate and the occurrence of specific mutations could not be proven for the early phase of lamivudine treatment.

Peginterferon plus ribavirin is standard therapy for adults with chronic hepatitis C. As no data are available for children, the aim of the study was to evaluate the efficacy and tolerability of peginterferon alfa-2b in combination with ribavirin in chronically infected children. Genotypes, alanine aminotransferase levels, and different routes of viral transmission were considered. In an open-labeled, uncontrolled pilot study, 62 children and adolescents (range, 2-17 years) were treated with subcutaneous peginterferon alfa-2b at a dose of 1.5 microg/kg body weight once per week plus oral ribavirin (15 mg/kg x day) for 48 weeks. Sixty-one patients completed the study. Twenty-three children discontinued therapy after 6 months according to study protocol. Sustained viral response was documented in 22 (47.8%)of 46 patients with genotype 1, in 13 (100%) of 13 with genotype 2 or 3, in 1 of 2 with genotype 4, in 19 (70.4%) of 27 children with parenteral, in 12 (48%) of 25 with vertical, and in 5 of 9 with unknown route of infection. Overall, treatment was well tolerated. Nevertheless, some side effects were present in all treated patients. Eighty-three percent had leucopenia, but only 3 individuals required dose reduction and 10.3% developed thyroid autoantibodies and thyroid dysfunction. In conclusion, combination treatment of peginterferon alfa-2b with ribavirin showed encouraging results and was well tolerated in children and adolescents with chronic hepatitis C. Weekly dosing of peginterferon alfa-2b is a considerable advance for this age group. The treatment is not approved for children. Further controlled trials are needed.

Journal of Pediatric Gastroenterology and NutritionVolume 40, Issue 5 p. 680-680 Abstracts: 38th Annual Meeting of the European Society for Pediatric Gastroentrology, Hepatology and Nutrition: Porto, Portugal, June 1-4, 2005 LONG TERM EFFICACY OF INTERFERON TREATMENT IN CHILDREN WITH CHRONIC HEPATITIS CAUSED BY A AND D HBV GENOTYPES PH2-08 L Szenborn, L Szenborn Department of Pediatric Infectious Diseases, Wroclaw University of Medicine, Wroclaw, PolandSearch for more papers by this authorI Kacprzak-Bergman, I Kacprzak-Bergman Department of Pediatric Infectious Diseases, Wroclaw University of Medicine, Wroclaw, PolandSearch for more papers by this authorI Zaleska, I Zaleska Department of Pediatric Infectious Diseases, Wroclaw University of Medicine, Wroclaw, PolandSearch for more papers by this authorP Wintermeyer, P Wintermeyer Children & #8217;s Hospital, Helios Klinikum Wuppertal, Witten-Herdecke University, Wuppertal, GermanySearch for more papers by this authorP Gerner, P Gerner Children & #8217;s Hospital, Helios Klinikum Wuppertal, Witten-Herdecke University, Wuppertal, GermanySearch for more papers by this authorS Wirth, S Wirth Children & #8217;s Hospital, Helios Klinikum Wuppertal, Witten-Herdecke University, Wuppertal, GermanySearch for more papers by this author L Szenborn, L Szenborn Department of Pediatric Infectious Diseases, Wroclaw University of Medicine, Wroclaw, PolandSearch for more papers by this authorI Kacprzak-Bergman, I Kacprzak-Bergman Department of Pediatric Infectious Diseases, Wroclaw University of Medicine, Wroclaw, PolandSearch for more papers by this authorI Zaleska, I Zaleska Department of Pediatric Infectious Diseases, Wroclaw University of Medicine, Wroclaw, PolandSearch for more papers by this authorP Wintermeyer, P Wintermeyer Children & #8217;s Hospital, Helios Klinikum Wuppertal, Witten-Herdecke University, Wuppertal, GermanySearch for more papers by this authorP Gerner, P Gerner Children & #8217;s Hospital, Helios Klinikum Wuppertal, Witten-Herdecke University, Wuppertal, GermanySearch for more papers by this authorS Wirth, S Wirth Children & #8217;s Hospital, Helios Klinikum Wuppertal, Witten-Herdecke University, Wuppertal, GermanySearch for more papers by this author First published: 01 May 2005 https://doi.org/10.1002/j.1536-4801.2005.tb01267.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Volume40, Issue5May 2005Pages 680-680 RelatedInformation

Objective: Evaluation of systematic epidemiological data regarding clinical characteristics, sex distribution and autoantibody pattern in Caucasian children with autoimmune hepatitis (AIH).Study design: Data of 142 children presenting with AIH (97 girls and 45 boys) have been analysed for their clinical, serological, and histological profile.Results: Clinical findings were jaundice (58%), unspecific weakness (57%), anorexia (47%), abdominal pain (38%) and paleness (26%). One hundred and three children (73%) (68 girls, 35 boys, 1.9:1) had AIH type 1 and 35 patients (25%) (27 girls, 8 boys, 3:4:1) type 2 due to specific autoantibodies. Four children could not be classified. Histology of 122 children revealed active hepatitis in 64 (52%), cirrhosis in 46 (38%), and mild inflammatory activity in 12 individuals (10%). The most prevalent HLA type was B8.Conclusion: In our cohort the prevalence of AIH was half as frequent in boys as in girls. Type 1 was the most frequent diagnosis (73%) and was more prevalent in older children. Type 2 was equally age distributed. The clinical presentation of AIH in children was unspecific and type I and type II could only be differentiated by the determination of the specific autoantibodies. Ninety percent of patients presented with high inflammatory activity or liver cirrhosis. (c) 2004 Elsevier Ltd. All rights reserved.

Journal of Pediatric Gastroenterology and NutritionVolume 39, Issue S1 p. S184-S184 ABSTRACTS: Poster Session Abstracts P0335 VITAMIN E AS TREATMENT FOR CHRONIC HEPATITIS B IN CHILDHOOD: RESULTS OF A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL P. Gerner, P. Gerner Childrens Hospital, Helios Klinikum Wuppertal, Witten-Herdecke University, WuppertalSearch for more papers by this authorT. G. Wenzl, T. G. Wenzl Childrens Hospital, Aachen University, AachenSearch for more papers by this authorH. G. Posselt, H. G. Posselt Childrens Hospital, Frankfurt University, FrankfurtSearch for more papers by this authorA. Ballauff, A. Ballauff Childrens Hospital, Essen University, Essen, GermanySearch for more papers by this authorA. Krahl, A. Krahl Childrens Hospital, Frankfurt University, FrankfurtSearch for more papers by this authorM. Ahaus, M. Ahaus Childrens Hospital, Aachen University, AachenSearch for more papers by this authorP. Wintermeyer, P. Wintermeyer Childrens Hospital, Helios Klinikum Wuppertal, Witten-Herdecke University, WuppertalSearch for more papers by this authorS. Wirth, S. Wirth Childrens Hospital, Helios Klinikum Wuppertal, Witten-Herdecke University, WuppertalSearch for more papers by this author P. Gerner, P. Gerner Childrens Hospital, Helios Klinikum Wuppertal, Witten-Herdecke University, WuppertalSearch for more papers by this authorT. G. Wenzl, T. G. Wenzl Childrens Hospital, Aachen University, AachenSearch for more papers by this authorH. G. Posselt, H. G. Posselt Childrens Hospital, Frankfurt University, FrankfurtSearch for more papers by this authorA. Ballauff, A. Ballauff Childrens Hospital, Essen University, Essen, GermanySearch for more papers by this authorA. Krahl, A. Krahl Childrens Hospital, Frankfurt University, FrankfurtSearch for more papers by this authorM. Ahaus, M. Ahaus Childrens Hospital, Aachen University, AachenSearch for more papers by this authorP. Wintermeyer, P. Wintermeyer Childrens Hospital, Helios Klinikum Wuppertal, Witten-Herdecke University, WuppertalSearch for more papers by this authorS. Wirth, S. Wirth Childrens Hospital, Helios Klinikum Wuppertal, Witten-Herdecke University, WuppertalSearch for more papers by this author First published: 01 June 2004 https://doi.org/10.1002/j.1536-4801.2004.tb12765.x Submitted by: [email protected] Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume39, IssueS1June 2004Pages S184-S184 RelatedInformation