Belgian consensus on irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is characterised by recurrent abdominal pain related to defaecation or associated with altered stool frequency or consistency. Despite its prevalence, major uncertainties in the diagnostic and therapeutic management persist in clinical practice. METHODS: A Delphi consensus was conducted by 20 experts from Belgium, and consisted of literature review and voting process on 78 statements. Grading of recommendations, assessment, development and evaluation criteria were applied to evaluate the quality of evidence. Consensus was defined as > 80 % agreement. RESULTS: Consensus was reached for 50 statements. The Belgian consensus agreed as to the multifactorial aetiology of IBS. According to the consensus abdominal discomfort also represents a cardinal symptom, while bloating and abdominal distension often coexist. IBS needs subtyping based on stool pattern. The importance of a positive diagnosis, relying on history and clinical examination is underlined, while additional testing should remain limited, except when alarm features are present. Explanation of IBS represents a crucial part of patient management. Lifestyle modification, spasmolytics and water-solube fibres are considered first-line agents. The low FODMAP diet, selected probiotics, cognitive behavioural therapy and specific treatments targeting diarrhoea and constipation are considered appropriate. There is a consensus to restrict faecal microbiota transplantation and gluten-free diet, while other treatments are strongly discouraged. CONCLUSIONS: A panel of Belgian gastroenterologists summarised the current evidence on the aetiology, symptoms, diagnosis and treatment of IBS with attention for the specificities of the Belgian healthcare system.

NRF2 Alters Mitochondrial Gene Expression in Neonate Mice Exposed to Hyperoxia.

Approximately 1 in 10 newborns are born preterm and require supplemental oxygen (O2) in an extrauterine environment following birth. Supplemental O2 can induce oxidative stress that can impair mitochondrial function, resulting in lung injury and increased risk in early life pulmonary diseases. The nuclear factor-erythroid 2 related factor 2 (NRF2) protects the cells from oxidative stress by regulating the expression of genes containing antioxidant response elements and many mitochondrial-associated genes. In this study, we compared Nrf2-deficient (Nrf2-/-) and wild-type (Nrf2+/+) mice to define the role of NRF2 in lung mitochondrial genomic features in late embryonic development in mice (embryonic days, E13.5 and E18.5) versus birth (postnatal day 0, PND0). We also determined whether NRF2 protects lung mitochondrial genome parameters in postnatal mice exposed to a 72 h hyperoxia environment. We found Nrf2-/- embryonic lungs were characterized by decreases in mtDNA copies from E13.5 to E18.5. Interestingly, Nrf2-/- heteroplasmy frequency was significantly higher than Nrf2+/+ at E18.5, though this effect reversed at PND0. In postnatal mice exposed to hyperoxia, we identified three- to four-fold increases in mitochondria-encoded mitochondrial genes, which regulate oxidative phosphorylation. Overall, our findings demonstrate a potentially critical role of NRF2 in mediating long-term effects of hyperoxia on mitochondrial function.

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.

Topical application of mitomycin-C in oesophageal strictures.

BACKGROUND: Benign oesophageal strictures may occur as a complication of caustic ingestion or severe gastro-oesophageal reflux or as a sequela of oesophageal surgery and other fibrosing conditions. The traditional initial treatment of oesophageal strictures is intraluminal dilation; however, even if frequent, this occasionally may not provide adequate oesophageal lumen capacity or give significant symptom-free intervals, and restricturing after dilation is difficult and challenging. Topical postdilation application of an antifibrotic agent, mitomycin-C, in the treatment of an oesophageal stricture has been described. PATIENTS AND METHODS: Eight centres participated, with a total of 16 patients (4 girls), median age 48 (range 0-276) months. The causes of stricture were as follows: caustic (10), post-trachea-oesophageal fistula repair (2), peptic (2), Crohn disease (1), and dystrophic epidermolysis bullosa (1). The median (range) length and diameter of the strictures were as follows: 22 mm (8-50 mm) and 1.5 mm (1-6 mm). Of the 16 patients, 15 had undergone repeated dilations varying from 3 to more than 1000 (daily self-bouginage) before mitomycin-C, and the median interval between dilations was 4 weeks. Mitomycin-C 0.1 mg/mL was applied after dilation for a median time of 3.5 minutes and a median of 3 (1-12) times. RESULTS: Major success, both endoscopic and clinical improvement or cure, occurred in 10 of 16 patients. In 3 of 16 patients the interval period between dilations increased dramatically. Failure of therapy was considered in 3 of 16. All of the patients remained symptom free for a follow-up time of as long as 5 years. CONCLUSIONS: Postdilation application of topical mitomycin-C resulted in major success in 62.5% of patients and partial success in 19%, and it may be a useful strategy in oesophageal strictures of differing causes that are refractory to repeated perendoscopic dilation.

Effects of chronically elevated glucose levels on the functional properties of rat pancreatic beta-cells.

This study examines the effects of chronically elevated glucose levels on the survival and function of purified rat beta-cells. Prolonged exposure (9 days) of beta-cell aggregates to 20 mmol/l glucose did not lead to cell losses, but reduced the amount of insulin secreted in response to glucose. This decrease was not caused by cellular desensitization but resulted from the lower cellular insulin content after a prolonged imbalance between stimulated rates of insulin synthesis and release. Virtually all beta-cells exhibited a state of metabolic and biosynthetic activation, which was maintained for at least 2 h in glucose-depleted media. Their rates of protein and insulin synthesis were amplified by glucose, reaching (half-) maximal stimulation at lower glucose concentrations (2 and 5 mmol/l, respectively) than control cells cultured at 10 mmol/l glucose (5 and 10 mmol/l, respectively). As for insulin release, the net glucose effect on insulin synthesis was markedly reduced as compared with that in control cells. This was also the case after culture at 6 mmol/l glucose. In the latter condition, the lower glucose-inducible activities were caused by cellular desensitization, with 50% of the beta-cells unresponsive to glucose and the other 50% responding with a lower sensitivity (half-maximal stimulation at 7 mmol/l glucose). Comparison of beta-cells cultured at the three glucose concentrations indicated that prolonged exposure to elevated glucose levels increases the number of degranulated cells, of cells with a high proportion of immature insulin granules, and of cells with glycogen deposition-morphologic features previously described in conditions of hyperglycemia. It is concluded that chronic exposure (9 days) of rat beta-cells to elevated glucose levels induces a prolonged state of beta-cell activation and glucose hypersensitivity rather than a glucotoxicity or glucose desensitization. This shift in the functional state of the beta-cell population is responsible for a reduced insulin release in response to glucose, as observed in other conditions of prolonged exposure to high glucose levels.

The long-term effect of a partial whey hydrolysate formula on the prophylaxis of atopic disease.

At the age of 5 years, the prevalence of atopic manifestations was analysed in 58 formula-fed "at risk" infants because of a history of atopic disease in at least two first degree relatives. Infants were randomly assigned to receive either a partial whey-hydrolysate formula (n: 28) or a regular cow's milk formula (n: 30) during the first 6 months of life; thereafter, feeding was unrestricted. Only non-breastfed infants were included. The groups did not differ in risk factors or in known confounding factors possibly influencing the incidence of manifestations suggestive of atopic disease. At 6 months, the prevalence of cow's milk protein (CMP) sensitivity was significantly decreased in the hydrolysate group (7% versus 43%; P: 0.002). At the age of 12 (21% versus 53%; P: 0.029), 36 (25% versus 57%; P: 0.018) and 60 months (29% versus 60%; P: 0.016) there was still a significant difference in the number of atopic manifestations, if calculated cumulatively. There was no difference between the groups if only the new cases after the age of 6 months were considered. Eczema was less frequent in the whey-hydrolysate group, but only during the 1st year of life, suggesting a decreased prevalence of CMP sensitivity. During the first 6 months, diarrhoea of non-infectious origin occurred in 8/30 infants (27%) of the adapted formula group, and in no infant in the hydrolysate group. "Colic as single manifestation" was considered of "allergic" origin in 1/28 infants in the hydrolysate group, and in 4/30 infants in the adapted formula group.(ABSTRACT TRUNCATED AT 250 WORDS)

Successful management of recurrent pneumothorax in cystic fibrosis by localized apical thoracoscopic talc poudrage.

Thoracoscopic talc poudrage of the entire pleural surface constitutes successful treatment of recurrent pneumothorax in cystic fibrosis (CF); however, subsequent lung transplantation is seriously jeopardized due to the development of extensive pleural adhesions. We describe a 27-year-old patient with CF with recurrent right-sided pneumothorax, refractory to chest tube drainage and to chemical (tetracycline) pleurodesis, who was successfully treated with a localized, apical thoracoscopic talc poudrage, thereby preserving the possibility of subsequent lung transplantation.

A clinical trial with an "anti-regurgitation" formula.

To determine whether a new "anti-regurgitation formula" containing a bean gum preparation decreases the number of regurgitations and gastro-oesophageal reflux (GOR), we studied 20 infants from 1 week to 4 months of age, referred for evaluation of regurgitation, in a double-blind prospective study. The number of regurgitations decreased significantly in both the treatment group (the formula with thickening product, positional treatment, parental reassurance) and the placebo group (the same formula without thickening product, positional treatment, parental reassurance) (P 0.002 and 0.032, respectively). The results of a 24-h oesophageal pH monitoring, performed before and during treatment, showed a significant decrease in the percentage of time oesophageal pH was < 4.0 in the treatment group. It is concluded that conservative treatment of regurgitation in infants, consisting mainly of parental reassurance and postural therapy, is sufficient to obtain clinical remission in most patients. In addition, milk thickening products tend to improve clinical remission and contribute to the normalisation of some pH metric parameters.

Comparison of in situ hybridization and immunocytochemistry for the detection of residual beta cells in the pancreas of streptozotocin-treated diabetic rats.

The relative efficacy of immunocytochemistry versus in situ hybridization in identifying residual beta cells was studied in rats with streptozotocin-induced diabetes. Consecutive sections of pancreas of streptozotocin-treated diabetic rats and control animals were alternately subjected to in situ hybridization (synthetic oligonucleotides complementary to rat preproinsulin mRNA) and immunocytochemistry (monoclonal antibodies to insulin). The results obtained with both methods were quantitated with the use of computer-assisted image analysis, and the ratio of cells positive by immunocytochemistry to those positive by in situ hybridization was determined. Under normoglycaemic conditions the values obtained by immunocytochemistry correlated well with those obtained by in situ hybridization (immuno/in situ > 95%). In the streptozotocin diabetic animals, however, immunocytochemistry resulted in a distinct underestimation of the number of residual beta cells (immuno/in situ < 80%). This difference was even more striking in small islet cell clusters (< 100 microns) (immuno/in situ 20%). These results suggest that in situ hybridization for prohormone mRNA is the method of choice for the identification of residual or regenerating beta cells with very low insulin content. Caution should be used when interpreting quantitative data in diabetic conditions that are based exclusively on immunocytochemical detection methods.

Differences in glucose recognition by individual rat pancreatic B cells are associated with intercellular differences in glucose-induced biosynthetic activity.

In vitro incubated rat islet B cells differ in their individual rates of protein synthesis. The number of cells in biosynthetic activity increases with the glucose concentration. Flow cytometric monitoring of the cellular redox states indicated that islet B cells differ in their individual metabolic responsiveness to glucose. A shift from basal to increased NAD(P)H fluorescence occurred for 18% of the cells at 1 mM glucose, for 43% at 5 mM, and for 70% at 20 mM. The functional significance of this metabolic heterogeneity was assessed by comparing protein synthesis in metabolically responsive and unresponsive subpopulations, shortly after their separation by autofluorescence-activated cell sorting. The glucose-sensitive subpopulation exhibited four- to fivefold higher rates of insulin synthesis during 60-min incubations at 2.5-10 mM glucose. Its higher biosynthetic activity was mainly caused by recruitment of cells into active synthesis and, to a lesser extent, by higher biosynthetic activity per recruited cell. Cells from the glucose-sensitive subpopulation were larger, and presented a threefold higher density of a pale secretory vesicle subtype, which is thought to contain unprocessed proinsulin. It is concluded that intercellular differences in metabolic responsiveness result in functional heterogeneity of the pancreatic B cell population.

Prenatal diagnosis of congenital toxoplasmosis.

Prenatal diagnosis of congenital toxoplasmosis was attempted in 50 pregnant women at risk for giving birth to an affected child. Fifteen of these patients seroconverted during pregnancy and 35 had a high initial antibody level in their first serum sample. Prenatal diagnosis consisted of a combination of ultrasound screening, amniocentesis, and funipuncture at about 20 weeks' gestation. Diagnosis of congenital toxoplasmosis was based on a positive toxoplasma culture of amniotic fluid or fetal blood and on the presence of specific immunoglobulin M antibodies in fetal blood. In addition, alterations in fetal hematology, cellular immunology, and fetal liver tests were indicative of infection. Fetal infection was detected in six fetuses; two died in utero as a consequence of the infection and four were born after 37 weeks' gestation. Despite antibiotic treatment with pyrimethamine and sulfadiazine, one child has internal hydrocephalus and chorioretinitis and another has unilateral chorioretinitis. In the two other children, the disease is still subclinical. Of the 44 children born after a negative prenatal diagnosis, 35 have reached the age of 1 year; toxoplasma antibodies have disappeared in all of them. Investigation of the remaining nine children showed a decrease in toxoplasma antibodies, suggesting that none of them are affected. Prenatal diagnosis was never associated with fetal loss, and premature delivery occurred in only two cases. We conclude that prenatal diagnosis of congenital toxoplasmosis is safe and reliable.

Reducing occurrences of an asymmetrical tonic neck reflex.

A custom-designed foam rubber headpiece was used during lunch with a multiply handicapped child to reduce the occurrences of an asymmetrical tonic neck reflex. After the inappropriate reflex was inhibited, the apparatus was gradually faded out by cutting away sections of the rubber. Ultimately, the headpiece was completely eliminated and the asymmetrical tonic neck reflex maintained a zero level of occurrence during lunch periods. Concomitantly, there was an increase in correct bites of food.

Comparison of static balance in trainable mentally handicapped and nonhandicapped children.

While for 31 trainable mentally handicapped children and for 31 nonhandicapped (Mage 91.56 mo.), there were no differences in static balance on left or right legs, total balance time was significantly different between the two groups, confirming prior work which related motor proficiency to intelligence. The normal group showed significant positive correlations among height, weight, age, and measures of static balance but only age was not correlated with balance for the handicapped group.