Functional gastrointestinal disorders in infants: Practice, knowledge and needs of Australian pharmacists.

AIM: To determine the nature and extent of interactions between retail pharmacists and families of infants concerned about functional gastrointestinal disorders. METHODS: A 15-question online survey was developed that could be completed by retail pharmacists in approximately 5 min. This survey aimed to obtain information relating to the frequency of interactions with parents of infants seeking advice and/or information about colic, gastro-oesophageal reflux (GOR) or constipation in pharmacies; what recommendations and/or advice was given by the pharmacists; from where the pharmacists obtained their information and what guidelines/recommendations they would value; and demographic information. RESULTS: A total of 362 pharmacists from every state and territory within Australia completed the survey. Conversations with parents/carers about constipation at least once a week were reported by 85% of pharmacists, with the equivalent percentages for GOR and colic both being 76%. In the case of constipation, medication was recommended in 70% of cases, and a nutritional approach was recommended in 67% of cases. Medication was recommended in 81% of cases of suspected colic, significantly greater than nutritional advice at 50%. For possible GOR, recommendations were similar, with medication being suggested in 66% and nutritional advice in 68%. GOR guidelines were the most sought after, with 42% of pharmacists placing such guidelines as their number one need. CONCLUSIONS: This survey indicates the need for greater emphasis to be given to reassurance by health-care professionals involved in the management of functional gastrointestinal disorders in infancy, as well as consideration of the construction of easily accessible, evidence-based national guidelines.

Reduced Hepatocellular Expression of Canalicular Transport Proteins in Infants with Neonatal Cholestasis and Congenital Hypopituitarism.

OBJECTIVE: To assess whether prolonged neonatal cholestasis, described in congenital hypopituitarism and septo-optic dysplasia (SOD), is associated with altered expression of selected canalicular ectoenzymes and canalicular transport proteins. STUDY DESIGN: Children with congenital hypopituitarism (n = 21), SOD (n = 18), and cholestasis seen in our center over 26 years were reviewed. Histopathologic findings in archival liver biopsy specimens were assessed (n = 10) and in those with low/normal levels of serum γ-glutamyltransferase (GGT) activity despite conjugated hyperbilirubinemia, expression of canalicular ectoenzymes and canalicular transport proteins was evaluated immunohistochemically. RESULTS: Patients presented at a median age of 8 weeks (range 3-20 weeks) with median total bilirubin 116 µmol/L (45-287 µmol/L), GGT 95 IU/L (25-707 UI/L), and serum cortisol 51 nmol/L (17-240 nmol/L). All but 3 had low free thyroxin (median 9.6 pmol/L [6.8-26.9]) with increased thyroid-stimulating hormone levels (median 5.95 mU/L [<0.1-9.24]). Liver histologic features included moderate-to-severe intralobular cholestasis with nonspecific hepatitis, giant-cell transformation of hepatocytes, and fibrosis. In all, immunohistochemical staining for canalicular ectoenzymes and canalicular transport proteins revealed a degree of reduced expression, associated with normal serum GGT values in 6 of the 10 patients, and another 6 nonbiopsied infants with cholestasis also had low/normal serum GGT activity. Sequencing of ABCB11 and ATP8B1 performed in 6 of the biopsied patients did not identify pathogenic mutations. Following replacement therapy, biochemical evidence of hepatobiliary injury resolved in all children within a median period of 6 months. CONCLUSION: Hepatobiliary involvement in congenital hypopituitarism associated with SOD has a good prognosis, but its etiology remains uncertain. Immunohistochemical expression of canalicular transport proteins was reduced in available liver samples.

Infant gastro-oesophageal reflux disease (GORD): Australian GP attitudes and practices.

AIM: The aim of this study was to evaluate the attitudes and practices of Australian general practitioners (GPs) regarding infant gastro-oesophageal reflux disease (GORD) diagnosis and management. METHODS: A national cross-sectional survey, involving a random sample of currently practising Australian GPs (n = 2319) was undertaken between July and September 2011. GPs attitudes and management of infant GORD were surveyed via an online and paper-based 41-item questionnaire. RESULTS: In total, 400 responses were analysed (17.24% response rate). The majority of GPs employed empirical trials of acid-suppression medication and/or lifestyle modifications to diagnose infant GORD. GPs frequently recommended dietary modification despite the belief that they were only moderately effective at best. In addition, GPs frequently prescribed acid-suppression medication, despite concerns regarding their safety in the infant population. Other GP concerns included the lack of clinical guidelines and education for GPs about infant GORD, as well as the level of evidence available for the safety and efficacy of diagnostic tests and treatments. CONCLUSION: Despite the important role Australian GPs play in the diagnosis and management of infant GORD, high-level evidence-based guidelines for GPs are lacking. Consequently, GPs engage in diagnostic and management practices despite their concerns regarding the safety and effectiveness.

Characterization of core clinical phenotypes associated with recurrent proximal 15q25.2 microdeletions.

A recurrent proximal microdeletion at 15q25.2 with an approximate 1.5 megabase smallest region of overlap has recently been reported in seven patients and is proposed to be associated with congenital diaphragmatic hernia (CDH), mild to moderate cognitive deficit, and/or features consistent with Diamond-Blackfan anemia. We report on four further patients and define the core phenotypic features of individuals with this microdeletion to include mild to moderate developmental delay or intellectual disability, postnatal short stature, anemia, and cryptorchidism in males. CDH and structural organ malformations appear to be less frequent associations, as is venous thrombosis. There is no consistent facial dysmorphism. Features novel to our patient group include dextrocardia, obstructive sleep apnea, and cleft lip.

Hedgehog signalling is downregulated in celiac disease.

BACKGROUND: Celiac disease (CD) is a common autoimmune disorder of the small intestine that occurs in genetically predisposed individuals. Animal studies have suggested that the hedgehog (Hh) signalling pathway is involved in gut inflammation, injury and repair. OBJECTIVE: To examine the expression of components of the Hh signalling pathway in CD. METHODS: Children undergoing gastroscopy investigation for CD at Monash University (Victoria, Australia), and other children undergoing gastroscopy in whom small bowel pathology was not expected (ie, controls), were included in the present study. One histopathologist, who was blinded to the biopsy data, analyzed the biopsies and a diagnosis of CD was made according to standard Marsh criteria. From these samples, RNA was extracted and complementary DNA was synthesized using reverse transcription polymerase chain reaction. The levels of Hh ligand Sonic hh, Indian hh, protein patched homologue 1 (PTCH 1) and bone morphogenetic protein 4 (BMP4) messenger RNA were quantified by real-time polymerase chain reaction. Relative expression quantification was performed using the ΔΔCt method. RESULTS: Duodenal biopsies were collected from 37 children. There were 20 CD specimens and 17 normal controls. The relative expression of Sonic hh from CD patients was 58% lower than that of the controls; similarly, Indian hh expression was decreased in children with CD by 44%. Compared with controls, the expression of Hh receptor PTCH 1 decreased by 71% and the expression of the Hh target gene BMP4 by 42%. CONCLUSIONS: The expression of the Hh signalling pathway genes was consistently downregulated in untreated CD children. These results suggest that the Hh signalling pathway plays a role in the mucosal lesions encountered in CD.

Molecular investigations to improve diagnostic accuracy in patients with ARC syndrome.

Arthrogryposis, Renal dysfunction and Cholestasis (ARC) syndrome is a multi-system autosomal recessive disorder caused by germline mutations in VPS33B. The detection of germline VPS33B mutations removes the need for diagnostic organ biopsies (these carry a>50% risk of life-threatening haemorrhage due to platelet dysfunction); however, VPS33B mutations are not detectable in approximately 25% of patients. In order further to define the molecular basis of ARC we performed mutation analysis and mRNA and protein studies in patients with a clinical diagnosis of ARC. Here we report novel mutations in VPS33B in patients from Eastern Europe and South East Asia. One of the mutations was present in 7 unrelated Korean patients. Reduced expression of VPS33B and cellular phenotype was detected in fibroblasts from patients clinically diagnosed with ARC with and without known VPS33B mutations. One mutation-negative patient was found to have normal mRNA and protein levels. This patient's clinical condition improved and he is alive at the age of 2.5 years. Thus we show that all patients with a classical clinical course of ARC had decreased expression of VPS33B whereas normal VPS33B expression was associated with good prognosis despite initial diagnosis of ARC.

Acquisition of competence in paediatric ileocolonoscopy with virtual endoscopy training.

This study prospectively compared the rates of skill acquisition in ileocolonoscopy in 2 consecutive groups of trainees in paediatric gastroenterology, with 1 cohort exposed to virtual endoscopy. All paediatric gastroenterology trainees rotating through our department during a 7-year period between 1997 and 2004 were formally assessed while performing ileocolonoscopies using a trainer case-by-case method. Fourteen consecutive trainees with no previous experience of ileocolonoscopy were assessed. Comparison of rates of skill acquisition and lesion recognition using multiple linear regressions revealed a significant acceleration of achievement of endoscopic goals (P < 0.0001) in the group with prior exposure to virtual endoscopy.

Antenatal presentation of biliary atresia.

OBJECTIVES: To investigate the incidence, presence of associated anomalies, type of malformation, and natural history of children with biliary atresia (BA) who presented antenatally. Study design The database of 194 infants diagnosed with BA at our tertiary referral unit between 1991 and 2002 was reviewed for infants in whom routine antenatal ultrasound had revealed biliary cystic malformations (BCMs). A retrospective analysis of their medical records was undertaken. RESULTS: Nine infants (six girls) with BCM were identified (4.6% of total referred patients with BA); all were born after 37 weeks' gestational age and presented to us at a median age of 4 weeks (range, 1-14 weeks). The presence of the BCM was confirmed on postnatal ultrasonography. Median age at corrective surgery was 5 weeks (range, 2-16 weeks). At surgery, six patients had type III BA, including one with the biliary atresia-splenic malformation syndrome; two had type II BA; and one had type I BA. Postoperatively, the infants were followed for a median of 2 years (range, 6 months to 11 years). All infants successfully cleared their jaundice. CONCLUSIONS: Improved techniques in routine antenatal ultrasonography can allow early recognition of BCM. This study suggests that BCM noted antenatally may represent early presentation of both biliary atresia-splenic malformation and nonsyndromic BA.