Lactose and fructose malabsorption in children with recurrent abdominal pain: results of double-blinded testing.

AIM: To investigate malabsorption of lactose and fructose as causes of recurrent abdominal pain (RAP). METHODS: In 220 children (128 girls, mean age 8,8 [4.1-16.0] years) with RAP, hydrogen breath tests (H(2) BT; abnormal if ΔH(2) > 30 ppm) were performed with lactose and fructose. Disappearance of RAP with elimination, recurrence with provocation and disappearance with re-elimination, followed by a 6-month pain-free follow-up, were considered indicative of a causal relation with RAP. For definite proof, a double-blinded placebo-controlled (DBPC) provocation was performed. RESULTS: Malabsorption of lactose was found in 57 of 210, of fructose in 79 of 121 patients. Pain disappeared upon elimination in 24/38 patients with lactose malabsorption, and in 32/49 with fructose malabsorption. Open provocation with lactose and fructose was positive in 7/23 and 13/31 patients. DBPC provocation in 6/7 and 8/13 patients was negative in all. However, several children continued to report abdominal symptoms upon intake of milk or fructose. CONCLUSION: Lactose intolerance nor fructose intolerance could be established as causes of RAP, according to preset criteria including elimination, open provocation and DBPC provocation. However, in clinical practice, persistent feeling of intolerance in some patients should be taken seriously and could warrant extended elimination with repeated challenges.

Recurrent abdominal pain in 200 children: somatic causes and diagnostic criteria.

AIM: To establish to what extent somatic causes can be found in children referred to secondary care with recurrent abdominal pain. METHODS: For 2 years, all consecutive patients (age 4-16 years) fulfilling Apley criteria, referred to secondary care, were included. After a diagnostic work-up, stepwise therapeutic interventions were performed. A diagnosis was considered to be the cause of the pain when the patient became pain free following therapeutic intervention and remained so for at least 6 months. RESULTS: Two hundred and twenty children (128 F, 92 M; mean age 8.8 years) were enrolled, of which 20 were lost to follow-up. Spontaneous recovery was seen in 54 patients, (occult) constipation in 92 patients (of whom 18 also had a somatic cause), gastrointestinal infections in 40, food allergy in five, miscellaneous disorders in seven and uncertain diagnosis in 13. In five patients, stress most likely caused the pain. A total of 198 patients became pain free and remained so during follow-up (mean 18, range 6-60 months). CONCLUSION: In 200 children with recurrent abdominal pain, somatic causes were found in 26%. Laxative therapy was successful in 46%, resulting in nearly all patients with functional abdominal pain to become pain free. Eventually, 99% became pain free using a therapeutic intervention protocol.

Rotavirus enterotoxin NSP4 binds to the extracellular matrix proteins laminin-beta3 and fibronectin.

Rotavirus is the most important cause of viral gastroenteritis and dehydrating diarrhea in young children. Rotavirus nonstructural protein 4 (NSP4) is an enterotoxin that was identified as an important agent in symptomatic rotavirus infection. To identify cellular proteins that interact with NSP4, a two-hybrid technique with Saccharomyces cerevisiae was used. NSP4 cDNA, derived from the human rotavirus strain Wa, was cloned into the yeast shuttle vector pGBKT7. An intestinal cDNA library derived from Caco-2 cells cloned into the yeast shuttle vector pGAD10 was screened for proteins that interact with NSP4. Protein interactions were confirmed in vivo by coimmunoprecipitation and immunohistochemical colocalization. After two-hybrid library screening, we repeatedly isolated cDNAs encoding the extracellular matrix (ECM) protein laminin-beta3 (amino acids [aa] 274 to 878) and a cDNA encoding the ECM protein fibronectin (aa 1755 to 1884). Using deletion mutants of NSP4, we mapped the region of interaction with the ECM proteins between aa 87 and 145. Deletion analysis of laminin-beta3 indicated that the region comprising aa 726 to 875 of laminin-beta3 interacts with NSP4. Interaction of NSP4 with either laminin-beta3 or fibronectin was confirmed by coimmunoprecipitation. NSP4 was present in infected enterocytes and in the basement membrane (BM) of infected neonatal mice and colocalized with laminin-beta3, indicating a physiological interaction. In conclusion, two-hybrid screening with NSP4 yielded two potential target proteins, laminin-beta3 and fibronectin, interacting with the enterotoxin NSP4. The release of NSP4 from the basal side of infected epithelial cells and the subsequent binding to ECM proteins localized at the BM may signify a new mechanism by which rotavirus disease is established.

Colonic transit times and behaviour profiles in children with defecation disorders.

AIMS: To evaluate children referred for defecation disorders using the child behavioural checklist (CBCL). METHODS: A total of 215 patients were divided into three groups: 135 (5-14 years of age) with paediatric constipation (PC), 56 (5-17 years) with functional non-retentive faecal soiling (FNRFS), and 24 (5-16 years) with recurrent abdominal pain (RAP). Behavioural scores were correlated with colonic transit time (CTT) and anorectal function parameters (manometry and EMG). RESULTS: No significant differences in the mean CBCL scores were found among the three patient groups. However, children with PC and FNRFS had significantly more behavioural problems than the Dutch normative sample, while children with RAP had scores within the normal range. No significant differences were found between CTT in the patient groups, with respect to the CBCL. Similarly, no significant difference existed between children able or unable to relax their pelvic floor muscles during defecation attempts and their behaviour profiles. CONCLUSION: There seems to be no relation between colonic/anorectal function and specific behavioural profiles. On the other hand, children with defecation disorders show more behavioural problems than do controls.

Facilities and equipment in district general hospitals in the Netherlands: are we prepared for the critically ill paediatric patients?

OBJECTIVE: To evaluate the inventory for initial treatment of critically ill children. DESIGN: Prospective study. SETTING: Paediatric emergency settings in 15 major district general hospitals. METHODS: Using an "expert opinion" created by paediatric intensivists, all hospitals were visited twice to check the inventory. Firstly, to examine the initial site of emergency care for children coming from outside the hospital. Secondly, to visit other emergency sites. A total score below 75% of the optimum was considered as not optimally equipped. MAIN RESULTS: Equipment to meet "respiratory problems" was considered by the experts as most essential. Seventy five per cent of all emergency sites scored below 75% (4 of 11 paediatric departments, 1 of 15 emergency rooms. The emergency room was in all aspects significantly better equipped than the paediatric department. Major differences and variations in the inventory were identified between all hospitals. CONCLUSIONS: Emergency rooms are better equipped to meet the needs of critically ill paediatric patients coming from outside the hospital than the paediatric departments. Paediatricians involved in the treatment of children who become critically ill during their stay in the hospital (the "indoor" patients), have less equipment and medication on the paediatric department at their disposal than on their emergency room. Obviously, emergency care on the paediatric wards should be equipped at the same level as in the emergency room because for both locations the "golden hour" is critically important in final outcome.

Lysine kinetics in preterm infants: the importance of enteral feeding.

INTRODUCTION: Lysine is the first limiting essential amino acid in the diet of newborns. First pass metabolism by the intestine of dietary lysine has a direct effect on systemic availability. We investigated whether first pass lysine metabolism in the intestine is high in preterm infants, particularly at a low enteral intake. PATIENTS AND METHODS: Six preterm infants (birth weight 0.9 (0.1) kg) were studied during two different periods: period A (n = 6): 40% of intake administered enterally, 60% parenterally; lysine intake 92 (6) micromol/(kg x h); and period B (n = 4): 100% enteral feeding; lysine intake 100 (3) micromol/(kg x h). Dual stable isotope tracer techniques were used to assess splanchnic and whole body lysine kinetics. RESULTS: Fractional first pass lysine uptake by the intestine was significantly higher during partial enteral feeding (period A 32 (10)% v period B 18 (7)%; p<0.05). Absolute uptake was not significantly different. Whole body lysine oxidation was significantly decreased during full enteral feeding (period A 44 (9) v period B 17 (3) micromol/(kg x h); p<0.05) so that whole body lysine balance was significantly higher during full enteral feeding (period A 52 (25) v period B 83 (3) micromol/(kg x h); p<0.05). CONCLUSIONS: Fractional first pass lysine uptake was much higher during partial enteral feeding. Preterm infants receiving full enteral feeding have lower whole body lysine oxidation, resulting in a higher net lysine balance, compared with preterm infants receiving partial enteral feeding. Hence parenterally administered lysine is not as effective as dietary lysine in promoting protein deposition in preterm infants.

[Functional childhood gastrointestinal disorders. I. Chronic abdominal pain]. / Functionele gastro-intestinale ziektebeelden op de kinderleeftijd. I. Chronische buikpijn.

Chronic abdominal pain occurs in 17% of children aged 0-14 years with a peak of 33% at the age of 7 years. According to the Rome II criteria abdominal pain disorders can be classified as functional dyspepsia, irritable bowel syndrome, functional abdominal pain, abdominal migraine, and aerophagia. This new classification will hopefully lead to a more careful diagnosis of functional abdominal pain syndromes and to better treatment strategies. A thorough history taking and physical examination are the cornerstone of diagnostic workup in children with chronic abdominal pain. An extensive explanation and reassurance are the basis of an adequate treatment and in the majority of cases this is successful.

[Functional childhood gastrointestinal disorders. II. Constipation and solitary encopresis: physiology and pathophysiology]. / Functionele gastro-intestinale ziektebeelden op de kinderleeftijd. II. Obstipatie en solitaire encopresis; fysiologie en pathofysiologie.

The childhood prevalences of constipation and encopresis are 0.3-8% and 1-3% respectively. Following a recent stricter definition and classification, constipation and solitary encopresis are now recognised to be two separate entities. Constipation is characterised by infrequent defecation, often in combination with involuntary loss of faeces. Solitary encopresis most often occurs once a day after school hours. When there is no defecation, the frequency of encopresis increases, the abdominal pain becomes more severe and the appetite becomes less, until a large quantity of faeces is produced (often once per week). The physiology of the defecation and continence mechanism is complex and has only been unravelled in part. The multiple physiological mechanisms involved have a complementary and compensatory effect on each other. This makes it difficult to determine the underlying pathophysiological mechanisms of these functional disorders.

[Functional childhood gastrointestinal disorders. III. Constipation and solitary encopresis; diagnostic work-up and therapy]. / Functionele gastro-intestinale ziektebeelden op de kinderleeftijd. III. Obstipatie en solitaire encopresis; diagnostiek en therapie.

A detailed medical history in combination with a thorough physical examination, including rectal examination, form the cornerstone in the diagnostic work-up for children with functional defecation disorders. Additional investigations are often not informative and have only minor diagnostic or therapeutic implications. Medical therapy in children with functional constipation and solitary encopresis is primarily based on clinical experience. In both patient groups, the role of education, the use of diary cards and toilet training is important. In some patients behaviour interventions are important. Oral laxatives are the basis of treatment of children with functional constipation, whereas they are contra-indicated in children with solitary encopresis. In both groups, biofeedback training appears to be of little additional benefit. Long-term follow-up of children with functional defecation disorders shows that complaints continue far beyond puberty in many children.

Gastric-type mucin and TFF-peptide expression in Barrett's oesophagus is disturbed during increased expression of MUC2.

AIMS: Barrett's oesophagus constitutes metaplastic epithelium, often diagnosed by mucin histochemistry. We determined the mucins and trefoil factor family (TFF)-peptides that were expressed in Barrett's oesophagus, in order to study changes in protein expression in early stages of Barrett's oesophagus development. METHODS AND RESULTS: Biopsy specimens of 71 Barrett's oesophagus patients were collected, and sections were stained for secretory mucins by histochemistry. Immunohistochemistry was performed for secretory mucins (MUC2, MUC5AC, MUC5B, MUC6), TFFs (TFF1, TFF2, TFF3), and proliferation (Ki67). Protein expression in the tissue was measured semiquantitatively. MUC5AC and TFF1 showed high levels and strong colocalization in the surface epithelium, whereas MUC6, MUC5B and TFF3 were found in the deeper glandular structures. TFF2 was found in both surface and glandular epithelium. The co-ordinate expression patterns of these six markers were similar to gastric antrum epithelium. MUC2 expression was ubiquitously associated with goblet cells within intestinal metaplasia, occurring in 68% of patients, and was correlated with increasing proliferation in the epithelium. CONCLUSIONS: Virtually all cells in Barrett's oesophagus epithelium displayed a secretory phenotype, demonstrating a co-ordinate gastric-type MUC and TFF expression. When MUC2 expression was more pronounced, the expression patterns of the other MUCs and the TFFs were increasingly disturbed. MUC2 expression may constitute a marker for early change in the phenotype of Barrett's oesophagus as a precancerous lesion.

Availability and usability of data for medical practice assessment.

OBJECTIVE: We analyzed availability and usability of the electronic patient data required for assessment of medical practice for a specific patient group. DESIGN: Case study in which physicians defined performance indicators and additional exploratory information. Data availability in the hospital information system was determined. Data usability was evaluated based on reason for recording, administrative procedures, and comparison with paper data. SETTING: A 155 bed pediatric department in a public academic medical center. STUDY PARTICIPANTS: Pediatricians and children with suspected meningitis. MAIN OUTCOME MEASURES: Availability and usability of electronic patient data. Usability criteria were standardization, completeness, and accuracy. RESULTS: A total of 14 performance indicators were defined. Of 39 data items required for indicator quantification, 29 were available, and 19 were usable without manual handling. Completeness and accuracy of the registration of reason for admission and discharge diagnoses were insufficient, leading to problematic patient selection and complication detection. Time-points of patient events were inaccurate or not available. Data regarding outpatient diagnosis, signs and symptoms, indications for test ordering, and medication administration were missing. Test result reports were not adequately standardized. Based on electronic patient data, five out of 14 performance indicators could be quantified reliably, but only after patient selection problems were overcome. For exploratory information, 16 out of 25 required data items were available and 13 were usable. CONCLUSIONS: Availability and usability of electronic patient data are insufficient for physician-led and detailed assessment of medical practice for specific patient groups. Extended registration of the reason for admission will improve patient selection and assessment of diagnostic process.

[Few ethnic differences in acute pediatric problems: 10 years of acute care in the Sophia Children's Hospital in Rotterdam]]. / Geringe etnische verschillen in spoedeisende problemen bij kinderen: 10 jaar acute hulp in het Sophia Kinderziekenhuis te Rotterdam.

OBJECTIVE: To evaluate whether there are differences in acute general paediatric problems and their severity between children with different ethnic backgrounds. DESIGN: Descriptive. METHOD: The following information was registered for patients who visited the paediatric emergency department at the Sophia Children's Hospital in Rotterdam, the Netherlands (1988 through to 1997): demographics, reason for encounter, diagnoses, diagnostics performed and follow-up. Ethnicity was determined by patient's surname. Analyses were performed using the chi 2 test, non-parametric Kruskal-Wallis test and multiple logistic regression. RESULTS: Fifty-one percent of all patients belonged to one of the ethnic minority groups. Infection-related problems were seen more often in Turkish (45%) and Moroccan (46%) children than in Dutch children (41%). Of those children with infection-related problems, the Turkish children were less likely to need X-rays (odds ratio: 0.73), laboratory diagnostics (0.72), an outpatient follow-up (0.79) or hospital admission (0.74). On the other hand, Moroccan paediatric patients were admitted slightly more frequently (to the intensive care department) and were more likely to have a lower respiratory tract infection (1.65). CONCLUSIONS: There were some differences between Dutch children and ethnic minorities in terms of the reasons for encounter and the severity of the problem. Compared with Dutch children, Turkish children presented with less severe infection-related problems, while Moroccan children had more severe infection problems.

The effect of anorectal manometry on the outcome of treatment in severe childhood constipation: a randomized, controlled trial.

OBJECTIVE: Approximately 50% of constipated children contract rather than relax the external sphincter complex during a defecation attempt. Although biofeedback training (BF) is able to change this defecation behavior, there is no additional effect of BF to conventional treatment (CT) on clinical outcome compared with CT alone. It has been postulated that the absence of a significant difference between these 2 treatment options might be because of a therapeutic, "demystifying" effect of performing anorectal manometry in conventionally treated children, necessary to obtain basal manometric data. The objective of this prospective, controlled, randomized study was to evaluate the effect of CT with 2 anorectal manometry sessions compared with CT alone (dietary advice, diary, toilet training, oral laxatives, and enemas) on clinical outcome. METHODS: A total of 212 constipated children (143 boys) who were visiting a referral pediatric gastroenterologic practice were randomized prospectively to CT alone (115 patients) or to CT combined with 2 manometry sessions (CTM; 97 patients). Patients were included in the study when they fulfilled at least 2 of the 4 following criteria: stool frequency fewer than 3 per week, 2 or more soiling and/or encopresis episodes per week, periodic passage of very large amounts of stool every 7 to 30 days, or a palpable rectal or abdominal fecal mass. CT comprises dietary advice, a daily diary, toilet training, and oral laxative treatment preceded by rectal disimpaction with enemas on 3 consecutive days. During both manometries, the child and the parent could watch the tracing on the computer screen. No explanation was given to either the child or the parents during the procedure. When the procedure was finished, the tracings were clarified. Successful treatment was defined as a defecation frequency of 3 or more per week and fewer than 1 soiling/encopresis episode per 2 weeks and no use of laxatives. RESULTS: Only 4 and 2 children from the CT and CTM groups showed no soiling and/or encopresis, whereas 76% and 65%, respectively, reported the periodic passage of large stools. In 26% and 30% of the patients, a rectal scybalum was found on physical examination. The success rates at 6, 26, 52, and 104 weeks' follow-up were 4%, 24%, 32%, and 43% and 7%, 22%, 30%, and 35% in the CT and CTM group, respectively. No significant difference in success percentage was observed between the 2 groups at any time of follow-up with relative risks (CT/CTM) and 95% confidence intervals, respectively, of 0.55 (0.16-1.89), 1.13 (0.67-1.89), 1.07 (0.69-1.65), and 1.23 (0.81-1.85). A significant increase in defecation frequency was observed between the first (intake) and second visits, which was sustained at all subsequent visits and stages of follow-up in both groups (not significant). Also in relation to the first visit, a significant decrease in encopresis episodes was shown and a further slow but significant decrease at 52 weeks of follow-up in both groups. The manometric data obtained from the CTM group showed a low percentage of children with normal defecation dynamics, namely 28%, which (significantly) increased to 38% at the last manometry. CONCLUSIONS: Anorectal manometry combined with CT compared with CT alone did not result in higher success rates in chronically constipated children. Therefore, anorectal manometry has no additional demystifying or educational effect on clinical outcome in chronically constipated children. This observation together with the observation in the current and previous studies that no correlation was found between (achievement of) normal defecation dynamics and success and that no relation was observed between volume of urge or critical volume and success leaves no diagnostic or therapeutic role for anorectal manometry in chronic constipated children, except its use as a diagnostic test to exclude Hirschsprung's disease. A simple CT is successful in 30% of severely constipated children who are referred to a tertiary hospital, underscoring the importance of long-lasting and adequate laxative treatment.

Lack of benefit of laxatives as adjunctive therapy for functional nonretentive fecal soiling in children.

OBJECTIVES: To determine whether the combination of laxative treatment and biofeedback therapy (BF) is more effective for management of functional nonretentive fecal soiling than biofeedback therapy alone. STUDY DESIGN: In a prospective nonblinded study, 48 children were randomized in 2 groups: treatment with oral laxatives (LAX) and 5 sessions of BF (BF + LAX) or 5 sessions of BF alone (BF) during a treatment intervention period of 7 weeks. Biofeedback was performed with perfused manometry catheters and rectal balloon distension. Training focused on awareness of balloon distension and instruction in correct defecation dynamics. Successful treatment was defined as <1 encopresis episode per 2 weeks. RESULTS: At the end of the intervention period, the number of encopresis episodes was significantly decreased in both groups: from 7 (2 to 24) to 2 (0 to 17) in the BF group and from 7 (3 to 25) to 2 (0 to 14) in the BF + LAX group. However, children given BF alone had significantly higher success rates than children treated with BF and additional oral laxatives (44% to 11%). CONCLUSIONS: There is no additional effect of laxative treatment in functional nonretentive fecal soiling. Children treated with BF in combination with laxatives showed a significantly lower success percentage compared with those treated with BF alone. These results suggest that children with functional nonretentive fecal soiling should be treated differently from children with constipation and encopresis.

Enteral inulin does not affect epithelial gene expression and cell turnover within the ileoanal pouch.

PURPOSE: This study evaluates the effects of enteral inulin on ileoanal pouch functioning by studying epithelial gene expression, cell turnover, and mucosal morphology. METHODS: Twenty patients with an ileoanal pouch received 24 g of inulin daily for three weeks, then a four-week wash-out period, and a placebo for three weeks. In this randomized, double-blind, crossover study, biopsy specimens of pouch mucosa were taken after each test period. Mucosal morphology, inflammation, epithelial proliferation, and cell death were assessed histologically. Expressions of proapoptotic and antiapoptotic regulators, intestinal fatty acid-binding protein, and mucin were quantified by Western blotting or enzyme-linked immunosorbent assay. The number of intestinal fatty acid-binding protein expressing cells was histologically assessed and a high iron diamine/Alcian blue staining was performed to discriminate between sulfated and nonsulfated acidic mucins. RESULTS: Inulin supplementation neither altered mucosal morphology nor influenced inflammation, epithelial cell proliferation, or cell death. The ratio between the proapoptotic and antiapoptotic regulators did not change after inulin supplementation. The number of intestinal fatty acid-binding protein-producing enterocytes and the intestinal fatty acid-binding protein expression level increased after inulin treatment, but did not reach statistical significance. The intestinal fatty acidbinding protein expression level correlated with the Pouchitis Disease Activity Index, which was at the brink of significance (P = 0.06). Mucin expression and the ratio between sulfated and nonsulfated acidic mucins were not altered by inulin supplementation. CONCLUSION: In this prospective study, inulin supplementation did not significantly alter pouch mucosal functioning because neither epithelial homeostasis nor epithelial gene expression was significantly altered by enteral inulin.

Selective sparing of goblet cells and paneth cells in the intestine of methotrexate-treated rats.

Proliferation, differentiation, and cell death were studied in small intestinal and colonic epithelia of rats after treatment with methotrexate. Days 1-2 after treatment were characterized by decreased proliferation, increased apoptosis, and decreased numbers and depths of small intestinal crypts in a proximal-to-distal decreasing gradient along the small intestine. The remaining crypt epithelium appeared flattened, except for Paneth cells, in which lysozyme protein and mRNA expression was increased. Regeneration through increased proliferation during days 3-4 coincided with villus atrophy, showing decreased numbers of villus enterocytes and decreased expression of the enterocyte-specific genes sucrase-isomaltase and carbamoyl phosphate synthase I. Remarkably, goblet cells were spared at villus tips and remained functional, displaying Muc2 and trefoil factor 3 expression. On days 8-10, all parameters had returned to normal in the whole small intestine. No methotrexate-induced changes were seen in epithelial morphology, proliferation, apoptosis, Muc2, and TFF3 immunostaining in the colon. The observed small intestinal sparing of Paneth cells and goblet cells following exposure to methotrexate is likely to contribute to epithelial defense during increased vulnerability of the intestinal epithelium.

Megarectum in constipation.

BACKGROUND: Faecal impaction is frequently observed in children with chronic constipation. The term megarectum is often used to describe this finding. AIM: To evaluate rectal functioning and rectal measures in constipated children with a filled rectum, in order to define the terms faecal impaction, enlarged rectum, and megarectum. METHODS: All children underwent radiological investigation, colonic transit time study, anorectal manometry, and rectal volume and rectal wall compliance measurements. Patients with faecal impaction were compared with controls, who had an empty rectum on digital rectal examination. RESULTS: A total of 31 patients and six controls were included in the study. The mean duration of complaints was 4.2 years and all had faecal incontinence. The colonic transit times in the patients showed a distinct delay in the rectosigmoid segment. Anorectal manometry was not significantly different between patients and controls. The rectal width in patients was 0.68 and in controls 0.52 with an upper limit of 0.61. The pressure-volume curve in patients showed significant less relaxation at a distension of 50 ml. The slope of the curve (corresponding with rectal wall compliance) was comparable for patients and controls. CONCLUSIONS: We suggest that faecal impaction is a filled rectum found on digital rectal examination; an enlarged rectum is defined by a rectopelvic ratio greater than 0.61; and megarectum is defined in those with significant abnormalities found with anorectal manometry, pressure-volume curves, or rectal compliance investigation. A diminished relaxation of the rectum on rectal distension could be the first sign of megarectum in children with chronic constipation.