Gastric emptying of solids in children: reference values for the (13) C-octanoic acid breath test.

BACKGROUND: (99m) Technetium scintigraphy ((99m) TS) is the 'gold standard' for measuring gastric emptying (GE), but it is associated with a radiation exposure. For this reason, the (13) C-octanoic acid breath test ((13) C-OBT) was developed for measuring GE of solids. The objective of this study was to determine normal values for gastric half-emptying time (t1/2 GE) of solids in healthy children. METHODS: Gastric emptying of a standardized solid test meal consisting of a pancake evaluated with (99m) TS and (13) C-OBT was compared in 22 children aged between 1 and 15 years with upper gastrointestinal symptoms. Subsequently, the (13) C-OBT was used to determine normal values for GE of the same solid test meal in 120 healthy children aged between 1 and 17 years. KEY RESULTS: The results showed a significant correlation (r = 0.748, p = 0.0001) between t1/2 GE measured with both techniques in the group of children with upper gastrointestinal symptoms. In the group of healthy children, mean t1/2 GE was 157.7 ± 54.0 min (range 71-415 min), but t1/2 GE decreased with age between 1 and 10 years and remained stable afterward. There was no influence of gender, weight, height, body mass index, and body surface area on t1/2 GE. CONCLUSIONS & INFERENCES: Normal values for GE of solids measured with the (13) C-OBT using a standardized methodology were determined in healthy children. We propose to use this method and corresponding reference ranges to study GE of solids in children with gastrointestinal problems.

Algorithms for managing infant constipation, colic, regurgitation and cow's milk allergy in formula-fed infants.

UNLABELLED: Gastrointestinal symptoms, such as constipation, regurgitation and infant colic, occur in about half of infants. These symptoms are often functional, but they may also be caused by cow's milk protein allergy. We developed three algorithms for formula-fed infants, which are consensus rather than evidence-based due to the limited research available in the existing literature. CONCLUSION: We believe that these algorithms will help primary healthcare practitioners to recognise and manage these frequent gastrointestinal manifestations in infants.

The use of probiotics in IBD and IBS.

While the role of microflora is well established in the development of inflammatory bowel disease (IBS); data is still emerging regarding IBS as the knowledge on brain-gut interaction grows. For both patient groups multiple efficacious treatments exist, but there are still unmet needs as long term disease control remains an issue. Given the importance of the microbiome on the development of the immune system and the interaction between the microbiome and the host organism, this "route" is being examined increasingly as a therapeutic possibility in both pathologies with variable results. We here provide a short overview on the existing data, meta-analysis and single studies, on probiotic treatment in both diseases.

Extensive protein hydrolysate formula effectively reduces regurgitation in infants with positive and negative challenge tests for cow's milk allergy.

AIM: Cow's milk protein allergy (CMPA) is treated using an elimination diet with an extensive protein hydrolysate. We explored whether a thickened or nonthickened version was best for infants with suspected CMPA, which commonly causes regurgitation/vomiting. METHODS: Diagnosis of CMPA was based on a positive challenge test. We compared the efficacy of two casein extensive hydrolysates (eCH), a nonthickened version (NT-eCH) and a thickened version (T-eCH), using a symptom-based score covering regurgitation, crying, stool consistency, eczema, urticarial and respiratory symptoms. RESULTS: A challenge was performed in 52/72 infants with suspected CMPA and was positive in 65.4%. All confirmed CMPA cases tolerated eCH. The symptom-based score decreased significantly in all infants within a month, and the highest reduction was in those with confirmed CMPA. Regurgitation was reduced in all infants (6.4 ± 3.2-2.8 ± 2.9, p < 0.001), but fell more with the T-eCH (-4.2 ± 3.2 regurgitations/day vs. -3.0 ± 4.5, ns), especially in infants with a negative challenge (-3.9 ± 4.0 vs. -1.9 ± 3.4, ns). CONCLUSION: eCH fulfilled the criteria for a hypoallergenic formula, and the NT-eCH and T-eCH formulas both reduced CMPA symptoms. The symptom-based score is useful for evaluating how effective dietary treatments are for CMPA.

Profile of pediatric Crohn's disease in Belgium.

AIM: A Belgian registry for pediatric Crohn's disease, BELCRO, was created. This first report aims at describing disease presentation and phenotype and determining associations between variables at diagnosis and registration in the database. METHODS: Through a collaborative network, children with previously established Crohn's disease and newly diagnosed children and adolescents (under 18 y of age) were recruited over a 2 year period. Data were collected by 23 centers and entered in a database. Statistical association tests analyzed relationships between variables of interest at diagnosis. RESULTS: Two hundred fifty-five patients were included. Median age at diagnosis was 12.5 y (range: 1.6-18 y); median duration of symptoms prior to diagnosis was 3 m (range: 1-12 m). Neonatal history and previous medical history did not influence disease onset nor disease behavior. Fifty three % of these patients presented with a BMI z-score < -1. CRP was an independent predictor of disease severity. Steroids were widely used as initial treatment in moderate to severe and extensive disease. Over time, immunomodulators and biological were prescribed more frequently, reflecting a lower prescription rate for steroids and 5-ASA. A positive family history was the sole significant determinant for earlier use of immunosuppression. CONCLUSION: In Belgium, the median age of children presenting with Crohn's disease is 12.5 y. Faltering growth, extensive disease and upper GI involvement are frequent. CRP is an independent predictive factor of disease activity. A positive family history appears to be the main determinant for initial treatment choice.

MR enterography in children with Crohn disease: results from the Belgian pediatric Crohn registry (Belcro).

INTRODUCTION: Magnetic Resonance enterography (MRE) is an imaging modality avoiding ionizing radiation and the discomfort associated with enteroclysis. The results of MRE at diagnosis in the patients of the Belgian pediatric Crohn registry (Belcro) are compared to endoscopical and histological results. METHODS: Results of MRE, endoscopy and histology were obtained from the medical charts and assigned to one of the following segments: jejunum, ileum, ascending colon, transverse colon, descending colon or rectosigmoid. MRE images were reviewed in a blinded way by 4 radiologists with specific interest in pediatric MRE. RESULTS: From the Belcro registry, twenty-two patients underwent a MRE during their work-up for Crohn disease. The results of endoscopy, histology and MRE were concordant (either all negative or positive) in the ileum in 16/18 patients and in the rectosigmoid, descending colon, transverse colon and ascending colon in resp 9, 8, 8 and 8/22 patients. In the non-concordant cases (MRE colon negative but endoscopy and/or histology positive), MRE could not reflect the subtle endoscopic or histologic lesions such as erosions that were described.In 4 cases where ileocaecal valve intubation was impossible ileal MRE findings were abnormal. MRE detected ileal stenosis, jejunal lesions and fistula in resp 4/22, 3/22 en 2/22 patients. The 100% and 75% interobserver agreement was resp 50-82% and 773-100% according to the different intestinal segments. CONCLUSIONS: MRE is a promising imaging modality avoiding radiation in Crohn disease. It should probably become the technique of first choice for the evaluation of extensive small bowel disease in children with Crohn disease.

Probiotics and prebiotics in infants and children.

Probiotics and prebiotics have a major influence on gastrointestinal flora composition. This review analyses the relationship between this change in flora composition and health benefits in children. Literature databases were searched for relevant articles. Despite exhaustive research on the subject in different indications, such as prevention and treatment of acute gastroenteritis, antibiotic associated diarrhea (AAD), traveler's diarrhea, inflammatory bowel disease, irritable bowel syndrome, Helicobacter pylori, necrotizing enterocolitis, constipation, allergy and atopic dermatitis, colic and extraintestinal infections, reports of clear benefits for the use of prebiotics and probiotics in pediatric disorders remain scarce. The best evidence has been provided for the use of probiotics in acute gastroenteritis and in prevention of AAD. However, AAD in children is in general mild, and only seldom necessitates additional interventions. Overall, the duration of acute infectious diarrhea is reduced by approximately 24 hours. Evidence for clinically relevant benefit in all other indications (inflammatory bowel disease, irritable bowel syndrome, constipation, allergy) is weak to nonexistent. Selected probiotic strains given during late pregnancy and early infancy decrease atopic dermatitis. Adverse effects have very seldom been reported. Since the risk seems minimal to nonexistent, prebiotics and probiotics may be helpful in the prevention and treatment of some disorders in children, although the evidence for benefit is limited. The best evidence has been accumulated for some lactobacilli strains and for Saccharomyces boulardii in the reduction of the duration of acute diarrhea due to gastroenteritis and prevention of AAD.

Safety and cost of infliximab for the treatment of Belgian pediatric patients with Crohn's disease.

Biologicals have become an important component in the treatment of Crohn's disease in children. Their increased and long term use raises safety concerns. We describe safety and cost of infliximab in Belgian pediatric Crohn's disease patients. All patients on infliximab as part of the present or past treatment for Crohn's Disease until January 1st 2011 were selected from an existing database. Information on disease phenotype, medication and adverse events were extracted. Adverse events occurred in 25.9% of patients exposed to infliximab of which 29.6% were severe. In total 31.7% of patients stopped infliximab therapy. The main reasons for discontinuation were adverse events in 45.4% and loss of response in 30.3%. No malignancies or lethal complications occurred over this 241 patient year observation period. Immunomodulators were concomitant medication in 75% of patients and were discontinued subsequently in 38.4% of them. The cost of infliximab infusions per treated patient per year in the Belgian health care setting is approximately 9 474 euro, including only medication and hospital related costs. Even though infliximab is relatively safe in pediatric CD on the short term, close follow-up and an increased awareness of the possible adverse reactions is highly recommended. Adverse reactions appeared in 25.9% of all patients and were the main reason for discontinuation. Treatment cost has to be balanced against efficacy and modifications in disease course. In the Belgian health care system, the medication is available to all patients with moderate to severe CD.

The Influence of Neocate in Paediatric Short Bowel Syndrome on PN Weaning.

Clinical management of short bowel syndrome remains a multistage process. Although PN is crucial, early introduction of enteral feeding is mandatory. We describe retrospectively 4 patients with an ultrashort bowel who could be weaned off PN on very short terms after introduction of an amino-acid-based formula (Neocate). Patient 1 had congenital short bowel with 50 cm small bowel and 30 cm colon. He had persistent diarrhoea on a semielementary formula. When Neocate was introduced he could be weaned from PN within 6 months. Patient 2 needed multiple surgical interventions because of NEC at D 27. He maintained 40 cm small bowel and an intact colon and remained PN dependent on semielemental formula. After introducing Neocate, PN could be weaned within 3 months. In the next 2 patients, Neocate was introduced as initial enteral feeding after bowel resection following antenatal midgut volvulus. Patient 3 had 20 cm small bowel and an intact colon. PN was weaned after 2 months. Patient 4 had 9 cm small bowel and an intact colon. PN was weaned after 13 months. In all patients Ileocaecal valve (ICV) was preserved. No consensus is reached on the type of formula to use for short bowel syndrome. Compared to recent data in the literature, the weaning period in these 4 patients was significantly shortened on an aminoacid based formula. The reason for this may lie in the antiallergic properties of this formula. We recommend the use of an amino-acid-based formula to induce earlier weaning of PN.

Presence, introduction and removal of mutagenic activity during the preparation of drinking water in the Netherlands.

A survey of the presence of mutagenic activity in drinking water of 18 cities in the Netherlands revealed that in drinking water of 13 cities mutagenic activity could be demonstrated. The activity was detected in the Ames test after concentrating the organic mutagens with a XAD-4/8 procedure. Dose-related responses were observed with concentrates corresponding to 0.5 to 3.0 liters of drinking water. A study of the changes in mutagenic activity during the preparation of drinking water in a few waterworks showed that breakpoint chlorination, transport chlorination and post chlorination increased the mutagenic activity, while ozonation only reduced the activity with metabolic activation. When adsorption on activated carbon powder was used, a certain reduction of mutagenic activity was observed. The use of activated carbon filters, however, removed the activity completely. The majority of organic mutagens present in drinking water concentrates were shown to be nonvolatile and relatively stable and probably consist of compounds with a molecular weight in the order of 200. These mutagens are not identical to the organics identified up till now in drinking water by standard gas chromatography/mass spectrometry analysis. Finally, a group of organic mutagens, which adsorbs only at pH 2-3 on XAD-4/8 (acid fraction), could be demonstrated in Ames-positive drinking waters.

Mutagenic activity associated with by-products of drinking water disinfection by chlorine, chlorine dioxide, ozone and UV-irradiation.

A retrospective epidemiological study in The Netherlands showed a statistical association between chlorination by-products in drinking water and cancer of the esophagus and stomach for males. A pilot-plant study with alternative disinfectants was carried out with stored water of the Rivers Rhine and Meuse. It was demonstrated that the increase of direct acting mutagens after treatment with chlorine dioxide is similar to the effect of chlorination. Ozonation of Rhine water reduced the mutagenic activity for Salmonella typhimurium TA 98 both with and without metabolic activation. UV alone hardly affects the mutagenicity of the stored river water for S. typh. TA 98. In all studies, practically no mutagenic activity for S. typh. TA 100 was found. Although remarkable changes in the concentration of individual organic compounds are reported, the identity of the mutagens detected is yet unclear. Compounds of possible interest due to their removal by ozonation are 1,3,3-trimethyloxindole, dicyclopentadiene and several alkylquinolines. Compounds which might be responsible for the increased mutagenicity after chlorination are two brominated acetonitriles and tri(2-chlorethyl) phosphate. Furthermore, the concentration procedure with adsorption on XAD resin and the subsequent elution step may have affected the results. It is proposed to focus further research more on the less volatile by-products of disinfection than on the trihalomethanes.

Toxicity assessment of organic compounds in drinking water in the Netherlands.

In a recent survey of organic compounds present in drinking water of twenty cities in The Netherlands, it was found that only a minor fraction (10%) of the total organic content could be identified. It appeared that drinking water prepared from polluted surface water contains more organic compounds with carcinogenic and mutagenic properties than water prepared from groundwater. The concentration of most of the organic constituents identified was generally below the microgram/litre level. It is not expected that circumstances will occur, that these compounds will be present in quantities, which are acutely toxic for consumers. On the other hand it cannot be excluded that certain organic compounds, in particular carcinogens and mutagens, may cause chronic toxic effects as a result of life time consumption of such contaminated drinking water. Therefore an epidemiological study was started in The Netherlands in which cancer mortality was related to the raw water source used for drinking water and the level of organic constituents. Preliminary results of the epidemiological study are presented. Furthermore a limited survey was carried out whereby drinking water of six cities was investigated for the presence of organic genotoxic compounds. The results of this survey led to the decision to extend this investigation to 19 cities. Finally, preliminary results regarding the characterization of the organic genotoxic compounds, present in drinking water, will be discussed.

Sensory evaluation of drinking water by consumer panels.

The human senses play an important role in assessing the quality of food and of the environment. Particularly the chemical senses of taste and smell determine the pleasantness of foods and drinks and may provide a warning mechanism for the presence of more or less toxic contaminants. Even after the recent rapid development of powerful analytical techniques the human nose can easily detect trace amounts of chemicals at levels many times lower than the analytical detection limits. Although taste and odour assessment of drinking water has been practiced in many waterworks laboratories by small panels, relatively unreliable results were obtained and such sensory data played up till now only a minor role in the management of the water treatment plant. More sophisticated and reliable methods for sensory water quality evaluation are discussed. Special attention is given to the characteristics of the human senses of taste and smell, to which the methodology of sensory assessment should be better adapted. High numbers of observations on a sample are generally needed, for which purpose the use of large panels has to be realized. In this respect the help of large consumer panels is an alternative for the presently often used small laboratory groups. As an example the preliminary results of a large ongoing experiment of sensory water quality assessment by 2 consumer panels of 100 persons each in the Rotterdam area are discussed. Drinking water quality is judged at the consumer homes every week. The experiment started September 1979 and will be continued for one year.