Pathological fractures in paediatric patients with inflammatory bowel disease.

UNLABELLED: Paediatric inflammatory bowel disease (IBD), especially Crohn's disease (CD), is commonly associated with poor skeletal health, related to the direct effects of chronic inflammation, prolonged use of glucocorticoid (GC), poor nutrition, delayed puberty and low muscle mass. Low bone mineral density is commonly reported, although the prevalence of long bone fractures may not be increased in these patients. Emerging evidence however suggests that there may be an increased risk of vertebral fractures (VFs) in this group. VFs presenting at diagnosis of paediatric CD, prior to any GC exposure, have been reported, highlighting the deleterious effect of inflammation on skeletal health. This paper reviews the published literature on pathophysiology of skeletal morbidity and fractures in paediatric IBD, illustrated with a new case report of multiple VFs in a prepubertal girl with CD, soon after diagnosis, who received minimal amounts of oral GC. Optimising control of disease, addressing vitamin D deficiency, encouraging physical activity and ensuring normal growth and pubertal progression are paramount to management of bone health in these patients. Despite the lack of evidence, there may be a place for bisphosphonate treatment, especially in the presence of symptomatic pathological fractures, but this requires close monitoring by clinicians with expertise in paediatric bone health. CONCLUSION: Chronic inflammation mediated by pro-inflammatory cytokines may have adverse effects on skeletal health in paediatric patients with IBD. The risk of vertebral fractures may be increased, even without exposure to glucocorticoid. Clinical monitoring of these patients requires careful attention to the various factors that impact on bone health.

Perspectives of paediatric and adult gastroenterologists on transfer and transition care of adolescents with inflammatory bowel disease.

BACKGROUND: Programmes specific to inflammatory bowel disease (IBD) that facilitate transition from paediatric to adult care are currently lacking. AIM: We aimed to explore the perceived needs of adolescents with IBD among paediatric and adult gastroenterologists and to identify barriers to effective transition. METHODS: A web-based survey of paediatric and adult gastroenterologists in Australia and New Zealand employed both ranked items (Likert scale; from 1 not important to 5 very important) and forced choice items regarding the importance of various factors in facilitating effective transition of adolescents from paediatric to adult care. RESULTS: Response rate among 178 clinicians was 41%. Only 23% of respondents felt that adolescents with IBD were adequately prepared for transition to adult care. Psychological maturity (Mean = 4.3, standard deviation (SD) = 0.70) and readiness as assessed by adult caregiver (Mean = 4, SD = 0.72) were prioritised as the most important factors in determining timing of transfer. Self-efficacy and readiness as assessed by adult caregiver were considered the two most important factors to determine timing of transition by both groups of gastroenterologists. Poor medical and surgical handover (Mean = 4.10, SD = 0.8) and patients' lack of responsibility for their own care (Mean= 4.10, SD = 0.82) were perceived as major barriers to successful transition by both paediatric and adult gastroenterologists. CONCLUSIONS: Deficiencies exist in current transition care of adolescents with IBD in Australia and New Zealand. Standardising transition care practices with strategies aimed at optimising communication, patient education, self-efficacy and adherence may improve outcomes.

Novel Burkholderiales 23S rRNA genes identified in ileal biopsy samples from children: preliminary evidence that a subtype is associated with perianal Crohn's disease.

A novel family of Burkholderiales bacteria was identified in ileal biopsy specimens from children presenting with symptoms of inflammatory bowel disease. A molecular subtyping approach based on sequencing of a variable region of the bacteria's 23S rRNA genes identified three variants. Pilot analysis identified one variant to be significantly associated with perianal Crohn's disease.

Hypnotherapy for treatment of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder of unknown aetiology. Current pharmacological treatments have limited value. Hypnotherapy has been reported to have beneficial effects for IBS symptoms. OBJECTIVES: To evaluate the efficacy of hypnotherapy for the treatment of irritable bowel syndrome. SEARCH STRATEGY: Published and unpublished randomised clinical trials and quasi-randomised clinical trials were identified through structured searches of MEDLINE (1966 to March 2006), EMBASE (1980 to March 2006), PsycINFO (1806 to March 2006), CINAHL (Cumulative Index to Nursing and Allied Health Literature, 1982 to March 2006), AMED (Allied and Complementary Medicine Database, 1985 to March 2006) and The Cochrane Central Register of Controlled trials. Conference proceedings from Digestive Disease Week (1980 to 2005) were also searched. SELECTION CRITERIA: Eligible studies included all randomised and quasi-randomised clinical studies comparing hypnotherapy for the treatment of irritable bowel syndrome with no treatment or another therapeutic intervention. DATA COLLECTION AND ANALYSIS: All studies were evaluated for eligibility for inclusion. Included studies were assessed for quality and data were extracted independently by four authors. The primary outcome measure of interest was the overall bowel symptom severity score which combines abdominal pain, diarrhoea or constipation and bloating. Secondary outcomes included abdominal pain, diarrhoea, constipation, bloating, quality of life, patient's overall assessment of well-being, psychological measures as per validated questionnaires, and adverse events. MAIN RESULTS: Four studies including a total of 147 patients met the inclusion criteria. Only one study compared hypnotherapy to an alternative therapy (psychotherapy and placebo pill), two studies compared hypnotherapy with waiting-list controls and the final study compared hypnotherapy to usual medical management. Data were not pooled for meta-analysis due to differences in outcome measures and study design. The therapeutic effect of hypnotherapy was found to be superior to that of a waiting list control or usual medical management, for abdominal pain and composite primary IBS symptoms, in the short term in patients who fail standard medical therapy. Harmful side-effects were not reported in any of the trials. However, the results of these studies should be interpreted with caution due to poor methodological quality and small size. AUTHORS' CONCLUSIONS: The quality of the included trials was inadequate to allow any conclusion about the efficacy of hypnotherapy for irritable bowel syndrome. More research with high quality trials is needed.

The effect of atrial natriuretic peptide on intestinal electrolyte transport.

The effect of atrial natriuretic peptide (ANP) on rat small intestinal electrolyte transport was examined. In vivo, intravenous administration of rat ANP(99-126) induced diuresis and natriuresis in conjunction with a significant decrease in intestinal water (basal, 37.1 +/- 5.7 versus ANP 28.5 +/- 6.0 microliters/cm per 20 min, P less than 0.05) and Na+ (4.0 +/- 0.7 versus 2.8 +/- 0.9 mumol/cm per 20 min, P less than 0.05) absorption (n = 9). In vitro, in Ussing chambers, in both jejunum and ileum, addition of 1.0 microM ANP to short circuited, stripped tissue produced a maximal increase in short circuit current and stimulated net Cl- secretion due to a significant increase in the unidirectional serosal to mucosal flux (JCl-sm: jejunum 17.4 +/- 1.3 versus 19.8 +/- 1.3 microEq/cm2 per h, P less than 0.01, n = 6; ileum 13.4 +/- 0.5 versus 17.2 +/- 0.6, P less than 0.01, n = 6) which was inhibited by the calcium channel antagonist verapamil (82 +/- 26%, P less than 0.05) and by the 5-HT2 receptor antagonist cinanserin (72 +/- 44%, P less than 0.05). Guanylate cyclase activity was stimulated by ANP in intact epithelium, but not in isolated crypt and villus enterocytes.

Physiological and psychosocial contributors to malnutrition in children with cystic fibrosis: review.

Malnutrition was once thought to be an inevitable consequence of cystic fibrosis (CF). It is now considered preventable but still contributes considerable morbidity in children. Malnutrition is linked to poorer pulmonary function, reduced survival and quality of life. As the anticipated lifespan of children with CF continues to lengthen, the prevention of malnutrition attains greater importance. This review explores the complex organic and psychosocial factors implicated in the aetiology of malnutrition associated with CF.

How to avoid complications during percutaneous endoscopic gastrostomy.

Percutaneous endoscopic gastrostomy (PEG) has advantages over open gastrostomy, and is an accepted technique for children. However, a number of technical problems may be encountered during insertion. This report identifies those problems and proposes precautions that can be taken to reduce their likelihood. Recognized major complications include esophageal injury, colonic perforation, wound infection, gastric erosion by the gastrostomy tube, and later symptomatic gastroesophageal reflux requiring correction by fundoplication.

Gastroesophageal reflux in children.

BACKGROUND: Gastroesophageal reflux is common in small children. It is important to recognise that its natural history and management differ from reflux in adults. OBJECTIVE: This article will summarise the clinical presentation, pathophysiology, appropriate investigations and therapy of reflux in small children. DISCUSSION: A small amount of regurgitation is common in infancy, and is only pathological if it results in harm. In children, reflux-induced injury can result from either acid exposure, nutrient loss or respiratory complications. Recognised presentations include heartburn, oesophagitis, infant irritability, dysphagia, haematemesis, stricture, growth failure, aspiration, apnoea and pneumonia. Excessive crying and irritable behaviour in infancy can be due to a variety of causes, but there is a fashionable tendency to assume that gastroesophageal reflux is a major factor. Regurgitation can be a symptom of other conditions such as infection or metabolic disturbance. It is important to carefully evaluate any infant with distressed behaviour to exclude a significant medical cause. Prolonged oesophageal pH monitoring is a very useful means of linking episodes of reflux with putative symptoms. The severity of gastroesophageal reflux tends to improve with age in infants and this should be considered when advising appropriate therapy, especially fundoplication.

Enteral nutrition in Crohn's disease: an underused therapy.

This paper reviews the literature on the history, efficacy, and putative mechanism of action of enteral nutrition for inflammatory bowel disease in both paediatric and adult patients. It also analyses the reasoning behind the low popularity of exclusive enteral nutrition in clinical practice despite the benefits and safety profile.

Gut flora and mucosal function.

The mucosal lining of the gastrointestinal tract is the route through which ingested nutrients are absorbed. It also serves to separate potentially toxic luminal contents and flora. These functions appear to be mutually incompatible, but are achieved by regional specialisations in epithelial structure and organ function. Enteric bacteria interact with enterocytes by influencing cellular electrolyte transport and tight junction permeability in the colon. The products of bacterial metabolism are essential for colonocyte nutrition.

The clinical significance of a prolonged stable pH around 4.0 in 24-h pH monitoring.

Esophageal acidity may remain stable for long periods at or near pH 4.0, potentially influencing the estimation of risk of esophagitis in esophageal pH monitoring assessment. Our aim was to determine the frequency and clinical significance of a prolonged stable pH around 4.0 (PSpH4) (pH 3.5-4.5) by retrospective examination of 503 pH records from children and by analysis of clinical information, pH parameters, motility studies, and esophageal biopsies. The frequency, duration, and proportion of total time with PSpH4 were quantified, and the ratio of the time for which the pH was < pH 4.0 during PSpH4 episodes to the total reflux time below pH 4.0 was calculated [stable/reflux (S/R) rate]. One hundred fifty-eight PSpH4 episodes were identified in 80 records. The average duration was 60 min and the S/R rate was 30%. Sixty-one percent of PSpH4 episodes started in the postprandial period (p < 0.05). Proportionally more episodes of PSpH4 occurred with an increased total percentage reflux time (p < 0.01). In recordings with PSpH4, the average number of reflux episodes remained normal, even when the percentage reflux time was > or = 10%. No correlation was shown between PSpH4 and esophageal dysmotility, esophagitis, cardiorespiratory symptoms, or prematurity. PSpH4 did not occur in recordings obtained after fundoplication. We conclude that PSpH4 is common and may result in an overestimation of risk of esophagitis. Qualitative assessment of pH monitoring is necessary along with conventional quantitative measurements.

A possible case of transient hereditary fructose intolerance.

A patient is described who presented with the signs and symptoms of hereditary fructose intolerance a few hours after her first fructose challenge. The diagnosis was confirmed by the demonstration of reduced activity of hepatic aldolase B towards fructose-1-phosphate. A second liver biopsy 10 months later had normal aldolase B activity towards fructose-1-phosphate and a fructose tolerance test was also normal. A possible explanation for these findings is proposed.

Hypernatraemic dehydration after Lucozade.

OBJECTIVE: To emphasise the dangers of inappropriate rehydration fluids in the treatment of gastroenteritis. CLINICAL FEATURES: A two-year-old girl was admitted to hospital in shock and unconscious. She had a 36-hour history of diarrhoeal illness and had received Lucozade. Therapy with this hypertonic fluid resulted in worsening diarrhoea and seizures. On examination she had hypernatraemic dehydration and decorticate posturing. INTERVENTION AND OUTCOME: An intravenous line was inserted, stable plasma protein solution was given, and she was admitted to the intensive care unit. Anticonvulsant and antibiotic therapy were begun. Significant neurological impairment was still evident after 14 days, at which time shw was discharged from hospital. Six months later she had made a good recovery, with no persisting neurological deficit. CONCLUSION: The inappropriate use of hypertonic fluids in gastroenteritis may be associated with significant electrolyte imbalances and neurological sequelae.

Dumping syndrome after Nissen fundoplication.

Dumping syndrome is infrequently reported in children, but has significant morbidity. It may be difficult both to diagnose and manage. Two children are reported who developed dumping syndrome after Nissen fundoplication. Symptoms occurred soon after the operation and included post-prandial pallor, sweating, lethargy and diarrhoea. Failure to thrive was a prominent feature. Typical biochemical changes included hyperglycaemia shortly after meals, followed by hyperinsulinaemia and reactive hypoglycaemia. Effective treatment was only achieved with continuous enteral feeding. Children undergoing fundoplication should be closely monitored for episodes of hypoglycaemia and unresponsiveness. The incidence of dumping syndrome after fundoplication may be underestimated, particularly in children.

Mucosal mast cells and developmental changes in gastric absorption.

We aimed to establish whether gastric mucosal mast cells undergo degranulation during normal postnatal development and to correlate this with gastric electrical parameters, paracellular permeability, and macromolecular absorption. Sprague-Dawley rats were studied between 10 and 30 days after birth. Gastric mucosal mast cell degranulation occurred and was maximal on days 15 and 17, measured by histology and gastric and serum levels of rat mast cell protease II. Short-circuit current, transepithelial conductance, and permeability of voltage-clamped glandular stomach were elevated in younger animals, falling with age except for a transient but significant increase in conductance and permeability at 17 days, closely correlated with maximal mast cell degranulation. Macromolecular uptake was significantly increased in animals aged 10-15 days. Concanavalin A and antigen-induced mast cell degranulation increased conductance and permeability in vitro in younger animals. We conclude that 1) gastric mucosal mast cells degranulate during development, 2) the neonatal stomach has increased permeability and uptake of macromolecules, and 3) gastric mucosal mast cell degranulation during development may affect mucosal permeability.

Modulation of distal colonic epithelial barrier function by dietary fibre in normal rats.

BACKGROUND: Dietary fibre influences the turnover and differentiation of the colonic epithelium, but its effects on barrier function are unknown. AIMS: To determine whether altering the type and amount of fibre in the diet affects paracellular permeability of intestinal epithelium, and to identify the mechanisms of action. METHODS: Rats were fed isoenergetic low fibre diets with or without supplements of wheat bran (10%) or methylcellulose (10%), for four weeks. Paracellular permeability was determined by measurement of conductance and 51Cr-EDTA flux across tissue mounted in Ussing chambers. Faecal short chain fatty acid (SCFA) concentrations were assessed by gas chromatography, epithelial kinetics stathmokinetically, and mucosal brush border hydrolase activities spectrophotometrically. RESULTS: Body weight was similar across the dietary groups. Conductance and 51Cr-EDTA flux were approximately 25% higher in animals fed no fibre, compared with those fed wheat bran or methylcellulose in the distal colon, but not in the caecum or jejunum. Histologically, there was no evidence of epithelial injury or erosion associated with any diet. The fibres exerted different spectra of effects on luminal SCFA concentrations and pH, and on mucosal indexes, but both bulked the faeces, were trophic to the epithelium, and stimulated expression of a marker of epithelial differentiation. CONCLUSIONS: Both a fermentable and a non-fermentable fibre reduce paracellular permeability specifically in the distal colon, possibly by promoting epithelial cell differentiation. The mechanisms by which the two fibres exert their effects are likely to be different.