Molecular analysis of the fructose transporter gene (GLUT5) in isolated fructose malabsorption.

Fructose, a naturally occurring monosaccharide, is increasingly used as an added sweetener in processed foods in the form of high fructose corn syrup. Increased fructose intake combined with the identification of children with clinical evidence of isolated fructose malabsorption (IFM) has stimulated interest in possible disorders of fructose absorption. The intestinal absorption of fructose is carried out by the facilitative hexose transporter, which has been designated as GLUT5. Functional properties and tissue distribution of GLUT5 suggest that IFM might be due to mutations in the GLUT5 gene. To test this hypothesis, we screened the GLUT5 gene for mutations in a group of eight patients with IFM and in one subject with global malabsorption, as compared with 15 healthy parents of subjects and up to 6 unrelated controls. No mutations were found in the protein coding region of this gene in any of the subjects. A single G to A substitution in the 5' untranslated region of exon 1 was identified in the subject with global malabsorption. This subject and her healthy mother were heterozygous for the variant sequence, suggesting that it was unlikely to be clinically significant. In addition, sequence analysis of each of the 12 GLUT5 exons was performed in the index case and confirmed the negative single-strand conformation polymorphism findings. These studies demonstrate that IFM does not result from the expression of mutant GLUT5 protein.

The small intestinal fructose transporters: site of dietary perception and evidence for diurnal and fructose sensitive control elements.

To obtain an insight into the mechanisms responsible for GLUT5 diurnality and fructose responsiveness, rats were gavaged at 9:00 AM or 6:00 PM with 1 g of fructose in the presence or absence of cycloheximide. After 4 h of fructose exposure, GLUT5 mRNA and protein levels increased 2-3.5-fold above the natural diurnal levels of expression. In situ hybridization and immunochemical analysis of GLUT5 mRNA and protein demonstrated that both diurnality and fructose responsiveness was confined to mature enterocytes. The protein synthesis inhibitor, cycloheximide, blunted the diurnal and fructose driven increase in GLUT5 mRNA expression in the morning, but had minimal effect on the pattern of expression in the evening. This differential sensitivity of intestinal GLUT5 mRNA to de novo protein synthesis may reflect the increasing presence of diurnal and fructose sensitive control factors during the day. Following vehicle gavage, Cycloheximide was more effective in reducing GLUT5 protein expression levels in the morning when compared to the evening. These data suggest that the turnover of GLUT5 protein may be diurnally influenced.

Management of acute gastroenteritis in Europe and the impact of the new recommendations: a multicenter study. The Working Group on acute Diarrhoea of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition.

BACKGROUND: The European Society for Paediatric Gasteroenterology, Hepatology and Nutrition (ESPGHAN) issued two sets of recommendations for the treatment of infants with acute gastroenteritis (1992, 1997). The purpose of this multicentre study performed in 29 European countries was to determine how closely current treatment compares with the ESPGHAN recommendations. METHODS: The outline of the study was based on a questionnaire that addressed the management of a 6-month-old infant with acute gastroenteritis complicated by mild to moderate dehydration. National coordinators circulated the questionnaire to randomly selected primary care physicians and to hospital-based paediatricians. RESULTS: A total of 2997 questionnaires were returned, of which 1768 were from Western Europe (WE) and 1229 from Central and Eastern Europe (CEE). Eighty-four percent of responding physicians said they would follow the ESPGHAN recommendation to use oral rehydration solution (ORS) for rehydration, with 66% using an ORS containing 60 mmol/l sodium ORS. Only 16% (WE 15%, CEE 19%) would follow the guidelines and use rapid oral rehydration over 3 to 4 hours. Forty-five percent would rehydrate infants in a 3- to 6-hour period (WE 35%, CEE 60%), and 17% (WE 23%, CEE 9%) would extend the rehydration period to 12 to 24 hours. ESPGHAN recommendation of rapid reintroduction of normal feeding after 3 to 4 hours of oral rehydration would be followed by only 21% of responding physicians, and only 43% (WE 46%, CEE 38%) would start feeding with full-strength formula. However, the guideline about continuation of breast-feeding is widely followed (total 77%; WE 78%, CEE 75%). Thirty-six percent (WE 45%, CEE 23%) use a lactose-containing formula after successful oral rehydration. Contrary to the ESPGHAN guideline 35% (WE 30%, CEE 42%) would use a lactose-free formula and 19% (WE 12%, CEE 28%) a lactose and cow's milk protein-free formula. Only 37% (WE 30%, CEE 46%) of responding physicians would follow the recommendation to use ORS to replace ongoing losses from watery diarrhoea. CONCLUSIONS: The results of the survey suggest that with the exception of recommending ORS for rehydration and continuation of breast-feeding during diarrhoea, a minority of responding European physicians follow the ESPGHAN guidelines for optimal management of children with acute gastroenteritis.

Chronic nonspecific diarrhea of childhood: pathophysiology and management.

Chronic nonspecific diarrhea, or toddler's diarrhea, is a frequently encountered disorder of defecation in otherwise healthy children. Although the precise pathophysiology remains to be elucidated, evidence suggests that toddler's diarrhea primarily is a gut motility disorder, modulated by dietary factors. Although the role of low-fat diets has since long been established, the liberal consumption of fruit juices and soft drinks is considered an equally important factor. Normalization of the child's diet, especially with regard to fat, fiber, fluids, and fruit juices, usually suffices to attain resolution of the diarrhea.

[A newborn infant with a tail]. / Een zuigeling met een staart.

A case of a male baby with a tail is described. The tail was surgically removed. Histopathological investigation showed that it was covered with hairless skin. It contained adipose and fibrous tissue, arteries, veins and nerves, but no cartilage, bone or muscle. In most cases of these caudal appendages surgical excision is sufficient, although an underlying anomaly should be excluded radiographically.

[Cisapride treatment for children with gastro-esophageal reflux]. / Gebruik van cisapride bij kinderen met gastro-oesofageale reflux.

The prokinetic drug cisapride is widely used for treating gastro-oesophageal reflux in infants and children. As in the Netherlands it is not officially registered for use in these age groups, prescribing doctors have problems obtaining adequate information on proper use and side effects. In the treatment of pediatric gastro-oesophageal reflux with cisapride the major recommendations include not to exceed the maximum dose of 0.2 mg/kg four times daily, to avoid comedication with imidazoles and macrolides and to check the QTc interval in patients with known risk factors for QTc prolongation.

[A child with puzzling complaints--does he have a disease?]. / Een kind met onbegrepen klachten--heeft het wel een ziekte?

Two children were presented to the physician with serious, long-lasting and unexplained complaints. The first was a girl aged four years with diarrhoea, vomiting and subfebrile temperature, the other was a boy aged almost 1 year with sudden spells of cyanosis and tachycardia. The mothers were found to falsify and fabricate the illness of their children: Münchausen syndrome by proxy. As a consequence of this behaviour, the children underwent extensive and sometimes invasive diagnostic investigations and treatment for their puzzling illness. A number of alarm signals associated with the condition, the parent and the child may help the physician to recognize and diagnose this syndrome at an early stage. Confrontation of the mother with the incriminating findings must take place under carefully prepared circumstances. The syndrome is related to the mothers' need for medical attention in order to retain a certain psychological balance. The fathers often have a passive role in the family life.

[Intraosseous infusions in children]. / Intraossale infusie bij kinderen.

Tibial intraosseous infusions can be invaluable in the management of the pediatric patient who is in cardiac arrest or severe shock when vascular access by the intravenous route is unattainable. Recently there has been renewed interest in this procedure. There is a small risk of complications.

[Fetal and neonatal outcome prolonged ruptured membranes in a gestational age of less than 24 weeks]. / Foetaal en neonataal beloop na langdurig gebroken vliezen bij een termijn van minder dan 24 weken.

The view appears to be generally held that the survival chances of fetuses in cases of very early rupture of the membranes are low. We report a retrospective study of 12 pregnancies with prolonged rupture of the membranes less than or equal to 24 weeks menstrual age. There was no significant maternal morbidity. After birth special attention was given to respiratory problems, deformities and infections. Four children were born at menstrual age less than 26 weeks. In all cases an intrauterine infection was found (chorioamnionitis). The eight children born greater than or equal to 26 weeks had good chances of survival despite oligohydramnios (all) and deformities (four). Severe intrauterine infections were not present in this group. An expectant obstetric management in cases of very early prolonged rupture of the membranes seems justified.

The duration of effect of infliximab maintenance treatment in paediatric Crohn's disease is limited.

BACKGROUND: Infliximab is effective for induction and maintenance of remission in children with moderately to severely active Crohn's disease (CD). AIM: To evaluate the long-term efficacy of infliximab treatment in paediatric CD. METHODS: In this observational, multicentre study, all paediatric CD patients in The Netherlands treated with infliximab from October 1992 to November 2009 and with minimal follow-up of 3 months since start of infliximab, were studied. RESULTS: One hundred and fifty-two CD patients [81M; median age at start of infliximab 15.0 years (IQR 13.1-16.4)] received a median number of 10.5 infliximab infusions (IQR 6-21). Median follow-up after start of infliximab was 25 months (IQR 13-40). Kaplan-Meier analysis showed that the cumulative probability of losing response to infliximab in patients who initially required repeated infusions was 13%, 40% and 50% after 1, 3 and 5 years, respectively. Seventy-four patients (49%) needed dose adjustments, with a median time to any adjustment of 6 months. CONCLUSIONS: Duration of effect of infliximab is limited as 50% of patients on infliximab maintenance treatment lose their therapeutic response after 5 years. Dose adjustments after start of infliximab are frequently needed to regain therapeutic benefit. These findings emphasise the need for effective, long-term treatment strategies for paediatric CD.

Fructose breath hydrogen tests in infants with chronic non-specific diarrhoea.

UNLABELLED: Clear fluids high in fructose (e.g., apple juice) have been incriminated for symptoms of chronic non-specific diarrhoea (CNSD), in particular in children 1-4 years of age. H2 breath tests were performed, after ingestion of fructose (1 g/kg), in 15 patients referred with CNSD and 35 controls. All 15 CNSD children (100%) had breath peak H2 of > or = 20 ppm versus 49% of the 35 controls (P = 0.0005). Median peak H2 in CNSD (90 ppm, range 31-136) was significantly higher than in controls (20 ppm, range 1-139) (P < 0.001). Orocoecal transit time in children with positive tests was similar in both groups. Similarly, median H2 increases during the test period had the same distribution. We demonstrated fructose malabsorption in CNSD, but found a great overlap with the control group. Our results strongly discourage the use of fructose breath H2 tests in children suspected of CNSD. A positive test has no diagnostic value and a negative test has no clinical implications. CONCLUSION: For clinical practice, we suggest a dietary history and a trial of appropriate measures in infants with chronic nonspecific diarrhoea, instead of performing the fructose H2 breath test.