Search

Paediatric gastroenterology in Australia has undergone remarkable changes over the more than six decades since Charlotte Anderson's pioneering work, and is now a well-established specialty in its own right. Australian paediatric gastroenterologists have made important contributions nationally and internationally.

Background Human Papillomavirus (HPV) causes significant burden of HPV-related diseases, which are more prevalent in immunosuppressed compared to immunocompetent people. We conducted a multi-centre clinical trial to determine the immunogenicity and reactogenicity of HPV vaccine in immunocompromised children. Here we present the immunogenicity results 5 years post vaccination. Methods We followed up immunocompromised children (5–18 years) with a range of specified underlying conditions who were previously recruited from three Australian paediatric hospitals. Participants received three doses of quadrivalent HPV vaccine (Gardasil Quadrivalent HPV Types 6, 11, 16, 18) and were followed up between 2007 and 2016 (60 months post-vaccination). The immunogenicity primary outcome was seroconversion and geometric mean titres (GMT) of the quadrivalent HPV vaccine serotypes in the study. Results Of the 59 original participants, 37 were followed up at 60 months. The proportion of participants who seroconverted were: 86.5%, 89.2%, 89.2%, 91.9% by competitive Luminex immunoassay (cLIA) and 83.8%, 83.8%, 94.6%, 78.4% by total immunoglobulin G assays (IgG) for serotypes 6, 11, 16 and 18 respectively. GMT values ranged from 118 (95%CI: 79–177) for serotype 11, to 373 (95%CI: 215–649) for serotype 16 by cLIA. For IgG, serotype 16 had the highest GMT of 261 (95%CI: 143–477) and serotype 18 had the lowest value of 37 (95%CI: 21–68). All antibody titres were lower in females compared to males but the difference was not statistically significant except for serotype 16. No serious adverse event was reported during this follow-up period. Conclusion Our evidence, although limited by small numbers, is reassuring that a three dose schedule of HPV vaccine remains immunogenic in immunocompromised children to five years post vaccination. Large scale studies are required to determine long term protection in immunocompromised children. Clinical trial registration: NCT02263703 (ClinicalTrials.gov).

Objective: To assess long term graft and patient survival after donor liver retransplantation in children in Australia and New Zealand during 1986–2017; to determine the factors that influence survival. Design: Retrospective cohort analysis (registry data). Setting, participants: Australia and New Zealand Liver Transplant Registry data for all liver retransplantations in children (under 18 years of age), 1986–2017, in all four paediatric and six adult liver transplantation centres in the two countries. Main outcome measures: Graft and patient survival at one, 5, 10 and 15 years. Results: 142 liver retransplantations were undertaken in children (59 during 1986–2000, 83 during 2001–2017). Kaplan–Meier survival analysis indicated that survival was significantly greater during 2001–2017 than 1986–2000 (P

Lower gastrointestinal endoscopy (LGIE)/colonoscopy is frequently performed for rectal bleeding, recurrent abdominal pain, and the diagnosis of inflammatory bowel disease (IBD). Although these are common indications, the causes of isolated rectal bleeding and recurrent abdominal pain in the otherwise well child have not been described.A retrospective analysis of patients who had had an LGIE/colonoscopy from January 2001 to December 2010 was performed. The following data were collected: demographic data, indication, distance reached, macroscopic findings, microscopic findings, diagnosis, additional procedures, and complications.There were a total of 999 colonoscopies. The colonoscopy was normal in 390 of 999 (39%). The commonest indication for colonoscopy was a diagnosis of suspected IBD, 449 of 999 (45%). IBD was confirmed in 282 of 449 (63%), but colonoscopy was normal in 143 of 449 (32%) of suspected IBD. Colonoscopy was performed for rectal bleeding in 197 of 999 (20%) of whom 141 of 197 (72%) were normal. There were 46 (5%) colonoscopies performed for recurrent abdominal pain, which were all normal. Our completion rate to the cecum and beyond was 521 of 999 (52%). Our perforation rate during the 10 years was 0.2%.Colonoscopy is a safe procedure in pediatrics; however, 39% of colonoscopies in this series were normal. Many of these could have been avoided by eliminating colonoscopy in patients with recurrent abdominal pain in the absence of other clinical features, conservative management with laxatives for those with fresh blood per rectum typical of anal fissures, and fecal calprotectin screening before endoscopy in patients with suspected IBD.

The aim of this study was to determine the immunogenicity and reactogenicity of HPV vaccine in immunocompromised children.A multi-centre clinical trial was conducted in three paediatric hospitals in Australia. Unvaccinated children 5-18years of age attending one of three paediatric hospitals with a range of specified conditions associated with immunosuppression were included. Quadrivalent HPV vaccine (Gardasil) was given to the participants and serum anti-HPV antibody levels were measured at baseline (before first dose), 7 and 24months after the first dose of vaccine.Fifty-nine participants were enrolled across the three paediatric hospitals and among those one was seropositive to types 6, 11 and 16 at baseline. Seven months after the first dose, seroconversion rates were 93.3%, 100%, 100% and 88.9% for type 6, 11, 16 and 18 respectively. The corresponding rates at 24month follow up were 82.2%, 91.1%, 91.1% and 68.9%. The greatest increase in geometric mean titre (GMT) was for type 16, followed by type 11. GMTs declined over the following months, but remained more than fourfold higher for all serotypes compared to baseline titres at 24months post vaccination. Injection site erythema, pain and swelling were commonly reported local adverse events and were less common after each dose. Few participants reported systemic adverse events, and minor disease flare occurred in two participants. One child developed a squamous cell oral carcinoma during follow up, but tissue was unable to be tested for HPV.Immunosuppressed children had an adequate immunogenic response to Quadrivalent HPV vaccine regardless of age and the cause of immunosuppression. HPV related cancers occur at higher frequency and earlier in immunosuppressed patients, so early vaccination and optimal scheduling should be further studied in such children.NCT02263703 (ClinicalTrials.gov).

OBJECTIVES Parenting stress, problems in family functioning, and lack of fathers' engagement in treatment are associated with poor quality of life in children with chronic illnesses. The aim of the present study was to examine these characteristics in families of infants with serious liver disease in Australia, to inform the provision of mental health care for these families. METHODS From September 2009 to May 2013, 42 parents of infants recently diagnosed as having serious liver disease (defined as liver disease that may require transplantation in the future) completed questionnaires about family function, impact of the infant's illness on the family, parent stress symptoms, and fathers' engagement in the care of the child. Participants were recruited from 4 metropolitan children's hospitals in Australia. RESULTS Parents reported psychological symptoms at similar rates to normative populations. Their reports of family functioning were significantly below mean scores in previously published populations with a medically ill family member (population mean 1.89; mothers mean 1.59; fathers mean 1.61, P < 0.001). Disruption to family roles was significantly correlated with psychological symptoms for mothers (r = 0.48, P < 0.01) and fathers (r = 0.31, P < 0.05). Greater helpfulness of fathers was correlated with lower depression in mothers (r = -0.35, P < 0.05), and fathers' anxiety was correlated with their increased engagement (r = 0.40, P < 0.01). CONCLUSIONS When parents report the presence of psychological symptoms, symptoms are likely to be present in both parents and are associated with difficulties adjusting to disrupted family roles. Father engagement may be protective of mothers' mental health.

Most infants with biliary atresia (BA) require liver transplantation (LT) after hepatoportoenterostomy (HPE), including those who initially clear jaundice. The aim of the present study was to identify clinical and routine laboratory factors in infants with BA post-HPE that predict native liver survival at 2 years.A retrospective cohort study was conducted in 217 patients with BA undergoing HPE in Sydney, Australia and Toronto, Canada between January 1986 and July 2009. Univariate and multivariate logistic regression using backwards-stepwise elimination identified variables at 3 months after HPE most associated with 2-year native liver survival.Significant variables (P 0.05) on univariate analysis included serum total bilirubin (TB) and albumin at 3 months post-HPE, bridging fibrosis or cirrhosis on initial liver biopsy, ascites of3 months post-HPE, type 3 BA anatomy, age at HPE of45 days, change in length z scores within 3 months of HPE, and center. On multivariate analysis, TB (P 0.0001) and albumin (P = 0.02) at 3 months post-HPE, and center (P = 0.0003) were independently associated with native liver survival. Receiver operating characteristic analysis revealed an optimal cut-off value of TB74 μmol/L (4.3 mg/dL; area under the receiver operating characteristic curve 0.8990) and serum albumin level35 g/L (3.5 mg/dL; area under the receiver operating characteristic curve 0.7633) to predict 2-year native liver survival. TB and albumin levels 3 months post-HPE defined 3 groups (1: TB ≤74 μmol/L, albumin35 g/L; 2: TB ≤74 μmol/L, albumin ≤35 g/L; 3: TB74 μmol/L) with distinct short- and long-term native liver survival rates (log-rank P 0.001). Length z scores 3 months post-HPE were poorer for group 2 than group 1 (-0.91 vs -0.30, P = 0.0217) with similar rates of coagulopathy.Serum TB and albumin levels 3 months post-HPE independently predicted native liver survival in BA when controlling for center. Serum albumin level35 g/L in infants with BA who were no longer jaundiced at 3 months post-HPE was a poor prognostic indicator. Poorer linear growth and absence of significant coagulopathy suggest a role for early aggressive nutritional therapy in this group.

The aim of the present study was to report caregiver perceptions to antireflux surgery and gastrostomy in children with severe neurological impairment and to report the complications of the surgery.Children were identified from a clinic database and clinical information and surgical complications were extracted from the database and hospital medical records. A cross-sectional questionnaire addressing severity of symptoms was administered to parents/caregivers and scored with a 5-point Likert scale (1 is much better to 5, much worse).A total of 122 children, median age 74 months (interquartile range 29-124), 63% spastic quadriplegic cerebral palsy, had antireflux surgery. Laparoscopic surgery was performed in 77 of 122 (63%) and 117 of 122 (96%) had gastrostomy insertion. Questionnaire was completed by 89 of 122 (73%) children; median duration of time from fundoplication to questionnaire was 77 months (43-89). The majority of caregivers indicated that surgery improved or greatly improved weight gain, chest infections, vomiting, and feeding tolerance. Only 2 caregivers reported that they regretted consenting to surgery. Serious surgical complications occurred in 10%.Serious complications were uncommon in this series of antireflux surgery in neurologically impaired children. Although gagging and retching were common following surgery, a high percentage of caregivers reported improved nutrition, reflux-related symptoms, and high levels of satisfaction.

OBJECTIVES: Research is lacking into the emotional effects on families of serious chronic illness in infants. We examined the effect of the diagnosis of serious liver disease in infants upon parent psychological symptoms and family functioning. We hypothesized that parent psychological symptoms, family functioning, and father engagement will predict infant emotional outcomes. METHODS: Parents of infants recently diagnosed with serious liver disease completed validated questionnaires about parent stress, family function, impact of the illness on the family, and father engagement. The measures were repeated after 1 year, with the addition of the Child Behavior Checklist (CBCL). RESULTS: Parents of 37 infants participated. Parent stress and family functioning scores were not elevated. Parent psychological symptoms, family function, and father engagement did not predict infant outcome. For mothers, infant diagnosis other than biliary atresia, number of outpatient visits, and impact of the illness on the family explained 32% of the variation in CBCL (P = 0.001). For fathers, socioeconomic status, infant diagnosis other than biliary atresia, whether the infant had had a transplant, and impact of the illness on the family explained 44% of the variation in CBCL (P

Aim The aim of this study was to measure resting energy expenditure (REE) and energy intake in children with quadriplegic cerebral palsy (CP), to relate these to anthropometric measurements, and to determine the influence of nutritional rehabilitation on REE. Methods Fifty-six children (20 females, 36 males; age range 3y 11mo-18y; mean age 10y; SD 3y 11mo) with CP (Gross Motor Function Classification System level V) participated in this cross-sectional study. Children were excluded if they had a known metabolic disorder, genetic syndrome, or chromosomal abnormality. Thirty-three of the children were tube fed and 23 were fed orally. A comparison group comprised 111 (42 females, 69 males) healthy children who had undergone anthropometric and REE measurements and were of similar age to the children with CP (4-19y). REE was measured by indirect calorimetry and energy intake was determined from weighed food records. Results The REE in the children with CP was low (79.5%) compared with that predicted and highly variable (SD 38.4%). Fat-free mass was the strongest predictor of REE, accounting for 27% of the variation. Energy intake as a percentage of REE in was greatly overestimated in oral-fed children with CP (293%). In a subset of children with CP (n=14), an increased energy intake by gastrostomy tube feeding resulted in an increase in REE from 70.0% to 101.9% of that predicted. Interpretation The REE of children with CP is low and variable and is not strongly related to any one anthropometric measurement. Food records in oral-fed children with CP are of little value owing to their inaccuracy. This study provided support for the hypothesis that the low REE found in malnourished children with CP is partly due to a low energy intake. © The Authors. Developmental Medicine & Child Neurology

Background: Given that members of Helicobacteraceae family colonize the intestinal mucus layer, it has been hypothesized that they may play a role in Crohn’s disease. This study investigated the presence of Helicobacteraceae DNA in biopsies collected from children with Crohn’s disease and controls. Materials and Methods: The presence of Helicobacteraceae DNA was investigated in intestinal biopsies collected from 179 children undergoing colonoscopy (Crohn’s disease n = 77, controls n = 102) using a Helicobacteraceae-specific PCR. Results: Members of the Helicobacteraceae were detected in 32/77 children with Crohn’s disease (41.5%) and 23/102 controls (22.5%). Statistical analysis showed the prevalence of Helicobacteraceae detected in patients to be significantly higher than that in controls (p = .0062). Analysis of non-pylori Helicobacteraceae showed that their prevalence was also significantly higher in patients than in controls (p = .04). Helicobacter pylori was detected in 14.0% of the biopsies across all groups. Given that all children tested were negative for gastric H. pylori, this was a surprising finding. Phylogenetic analysis of H. pylori sequences detected in the biopsies showed that the H. pylori strains identified in the patients did not group with gastric H. pylori included in the analysis, but rather with other H. pylori strains detected in the intestine, gall bladder, and liver. Conclusions: The higher prevalence of Helicobacteraceae DNA in Crohn’s disease patients would suggest that members of this family may be involved in this disease. In addition, phylogenetic analysis of H. pylori strains showed that extragastric sequences clustered together, indicating that different H. pylori strains may adapt to colonize extragastric niches.

CF liver disease is an uncommon indication for pediatric LT. Determining optimal timing and type (isolated liver versus multi-organ) of transplantation for those with severe liver disease can be challenging and involves consideration of the extent of liver disease (PHT, synthetic dysfunction) and extrahepatic factors such as pulmonary function. We present the experience of isolated LT for CF at our center. Eight children received one allograft each (3.9% of all grafts). One- and four-yr survivals are both 75%. The two deaths occurred within the first two months after LT, and in both cases, invasive fungal infections were implicated, one following treatment for acute severe rejection. All had significant PHT, and six had synthetic dysfunction. All had roux-en Y biliary anastomoses and none developed long-term biliary complications. Seven had pulmonary colonization with Pseudomonas aeruginosa and six with fungus at time of transplantation. Mean pre-LT FEV1 was 80% (range 59-116%) predicted, and lung function post-LT was stable. Isolated LT in children with CF is successful in those with relatively preserved pulmonary function, which does not appear to deteriorate as a consequence. Roux-en Y biliary anastomosis and antifungal prophylaxis should be a part of management of these patients.

Children aged between 4 and 18 years with spastic quadriplegic CP (Gross MotorFunction Classification System level V) were recruitedfrom the Children’s Hospital at Westmeadto participate in this prospective cohort study. The children had measurements of anthropometry(weight, height, and skinfold), bone mineral content (BMC) by dual-energy X-ray absorptiometry,and total body protein (TBP) by neutron activation analysis before and after gastrostomy tubefeeding. Comparison data were collected prospectively from age-matchedhealthy childrenandextractedfrom databases for this study.

In small infants and babies who receive split or living-related adult left lateral segmental liver grafts, further reduction (hyper-reduction) of the graft may be necessary to optimize the size of the graft for the child. We report our experience with hyper-reduction of adult left lateral segment grafts in nine children. A retrospective review of the medical records of children who received hyper-reduced grafts at the Children's Hospital at Westmead, Australia was performed. Of 215 liver transplants performed on 186 children between 1986 and May 2009, 147 were reduced grafts. Nine grafts were further reduced (hyper-reduced) after an on-table assessment of graft size relative to the available abdominal space was made. Mean graft size reduction was by 30%. The pledgetted technique of resection was used in four patients. All required delayed closure of the abdomen, and in three patients, fascial closure was not possible and a Surgisis patch (Cook Surgical International, West Lafayette, IN, USA) was placed to augment the abdominal capacity. Two children had hepatic artery thrombosis. One was successfully thrombectomized. In the other, technical problems with the donor liver contributed to death 10 days post-transplant. Two bile leaks, one from the cut surface and the other at the anastomotic site, were oversewn at the time of abdominal closure. On follow-up (median 33 months), two developed biliary strictures requiring dilatation. Hyper-reduction of segmental grafts can be safely performed when needed. In view of its versatility, it may be preferable to hyper-reduce a graft rather than use a monosegment graft. Comparable long-term results are possible. The pledgetted technique of resection is easy, quick, and safe. The fact that it can be performed after revascularization with minimal blood loss adds great flexibility to this technically challenging procedure.

The aim of this study was to examine the role of HA flow abnormalities in the development of biliary strictures following split liver transplants. Data was obtained from a prospective data base of all patients undergoing split liver transplants from 2000-2008 with a follow up time of at least six months. Forty-six transplants were performed in 44 patients. Fourteen of 46 developed strictures of whom four were intrahepatic and 10 anastomotic. Nine of 14 with strictures had either hepatic artery thromobosis (HAT, four) or abnormalities of HA flow identified by routine Doppler ultrasound (5) compared with two of 32 without strictures (p < 0.02, (one temporary loss of flow and one HA aneurysm). There were no differences between the stricture and non stricture group with regard to age or weight at transplant, donor age, cold and warm ischemia times or intraoperative portal vein flow though there was a significant decrease in intraoperative HA flow in the stricture group. In conclusion, both HAT and hepatic artery flow abnormalities are associated with biliary strictures in the majority of split liver transplants. However, unrecognised abnormalities in HA flow and or other factors are likely to contribute.

We report two children who presented with cough and wheeze, were initially misdiagnosed with asthma and were subsequently demonstrated to have achalasia as the underlying cause of their symptoms. These cases highlight the importance of considering diagnoses other than asthma when there is a suboptimal response to asthma medications, as well as the value of investigations including chest X-ray and pulmonary function tests in establishing the underlying cause.

Small bowel resection decreases brush border membrane (BBM) glucose uptake kinetics. Oral epidermal growth factor (EGF) returns net glucose transport across intact tissue to control levels despite persistence of a defect in BBM glucose uptake. The purpose of this study was to examine the effects of resection and EGF treatment on sodium-dependent glucose cotransporter 1 (SGLT-1) expression in distal remnant tissue. New Zealand White rabbits (1 kg) underwent 70% small bowel resection (R). One group of resected animals (R-EGF) received oral EGF (40 microg/kg, days 3-8). Distal remnant tissue was harvested 10 d after surgery, and compared with controls (C). Mucosal SGLT-1 mRNA was measured by Northern blot, BBM SGLT-1 content by Western blot, and villus distribution of SGLT-1 protein and mRNA by immunofluorescence and in situ hybridization. Western blot indicated BBM from both resected and EGF-treated tissue had decreased SGLT-1 content (C, 0.55 +/- 0.04; R, 0.35 +/- 0.04; R-EGF, 0.35 +/- 0.03 trace OD; n = 5; p0.05). Northern blot revealed no alterations in mucosal SGLT-1 mRNA content in any group. SGLT-1 protein and mRNA localization in control tissues was characterized by a gradual increase in stain intensity from the base of the villus to the villus tip. Resection altered SGLT-1 protein and mRNA expression along the villus axis with intensity being strongest in the mid-villus region and little expression at the tip of the villus. Oral EGF normalized SGLT-1 protein and mRNA expression to control patterns. Resection alters SGLT-1 protein and mRNA expression along the villus axis, despite no change in total mucosal SGLT-1 mRNA content. EGF normalized villus SGLT-1 protein and mRNA distribution, without altering overall BBM SGLT-1 content or mucosal mRNA levels.

Microfilaments have been reported to be polarized in a number of cell types based both on function and isoform composition. There is evidence that microfilaments are involved in the movement of vesicles and the polarized delivery of proteins to specialized membrane domains. We have investigated the composition of actin microfilaments in gastrointestinal epithelial cells and their role in the delivery of the cystic fibrosis transmembrane conductance regulator (CFTR) into the apical membrane using cultured T84 cells as a model. We identified a specific population of microfilaments containing the tropomyosin (Tm) isoforms Tm5a and/or Tm5b, which are polarized in T84 cell monolayers. Polarization of this microfilament population occurs very rapidly in response to cell-cell and cell-substratum contact and is not inhibited by jasplakinolide, suggesting this involves the movement of intact filaments. Colocalization of Tm5a and/or Tm5b and CFTR was observed in long-term cultures. A reduction in Tm5a and Tm5b expression, induced using antisense oligonucleotides, resulted in an increase in both CFTR surface expression and chloride efflux in response to cAMP stimulation. We conclude that Tm isoforms Tm5a and/or Tm5b mark an apical population of microfilaments that can regulate the insertion and/or retention of CFTR into the plasma membrane.

We aimed to assess the incidence of HAT over three eras following implementation of microvascular techniques and a customized anticoagulation protocol in a predominantly cadaveric split liver transplant program. We retrospectively reviewed pediatric liver transplants performed between April 1986 and 2016 and analyzed the incidence HAT over three eras. In E1, 1986-2008, each patient received a standard dose of 5 U/kg/h of heparin and coagulation profiles normalized passively. In E2, 2008-2012, microvascular techniques were introduced. In E3, 2012-2016, in addition, a customized anticoagulation protocol was introduced which included replacement of antithrombin 3, protein C and S, and early heparinization. A total of 317 liver transplants were completed during the study period, with a median age of 31.7 months. In E1, 22% of grafts were cadaveric in situ split grafts, while the second and third eras used split grafts in 59.0% and 64.9% of cases, respectively. HAT occurred in 9.5% in the first era, 11.5% (P=.661) in the second, and dropped to 1.8% in the third era (P=.043). A routine anticoagulation protocol has significantly reduced the incidence of HAT post-liver transplantation in children in a predominantly cadaveric in situ split liver transplant program.

BACKGROUND—The pathophysiology of enterohaemorrhagic Escherichia coli (EHEC) infection remains unclear. Eicosanoids have been implicated as pathophysiological mediators in other colitides. AIMS—To determine if prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) contribute to mucosal inflammation and dysfunction in EHEC colitis. METHODS—Ten day old rabbits were infected with EHEC. For five days after infection, mucosal synthesis of PGE2 and LTB4 was measured in distal colonic tissue from control and infected animals and 51Cr-EDTA permeability was assessed in vivo. Myeloperoxidase activity was measured and histological inflammation and damage were assessed at five days in control and infected animals and after treatment of infected animals with the LTB4 synthesis inhibitor MK-886. In separate experiments, ion transport was measured in Ussing chambers, before and after in vitro addition of the cyclooxygenase inhibitor indomethacin. RESULTS—LTB4 synthesis was increased from day 2 after infection onwards and PGE2 synthesis was increased on day 3. Mucosal permeability did not increase until day 5 after infection. MK-886 inhibited colonic LTB4 production but did not reduce diarrhoea, inflammation, or mucosal damage. Electrolyte transport was not significantly altered on day 3 after infection. However, both Cl secretion and reduced Na absorption found on day 5 were partially reversed by indomethacin. CONCLUSIONS—Tissue synthesis of PGE2 and LTB4 did not correlate temporally with EHEC induced inflammation or changes in mucosal permeability and ion transport. Cyclooxygenase inhibition partially reversed ion transport abnormalities but lipoxygenase inhibition did not affect mucosal inflammation or histological damage. We conclude that the contribution of eicosanoids to mucosal injury and dysfunction is more complex than previously suggested. Keywords: enterohaemorrhagic; Escherichia coli; electrolyte transport; prostaglandins; leukotrienes; chloride secretion

We present 4 brothers with developmental delay, minor anomalies, and symptoms due to gastrointestinal dysmotility. There was some resemblance with FG syndrome, although none of the brothers had sufficient findings to make this diagnosis. The index case presented with at age 1 month with screaming episodes, mild gastro-esophageal reflux (GER), and severe constipation. Esophageal manometry studies were consistent with the diagnosis of “nutcracker esophagus.” Symptomatic and manometric improvement followed treatment with oral calcium channel blockers. Two older and less severely affected brothers had similar manometric findings but did not require treatment. A fourth brother with symptoms in infancy now has normal esophageal manometry findings. These boys in all likelihood have an X-linked syndrome with manifestations of FG syndrome, in which treatment with calcium channel blockers, produces clinical and manometric improvement. The FG syndrome is an X-linked syndrome of multiple congenital anomalies/mental retardation with facultative manifestations of gastrointestinal dysmotility, including gastro-esophageal reflux, severe feeding difficulties, and constipation. Esophageal dysmotility, in particular “nutcracker esophagus,” should be suspected in infants with the FG syndrome and screaming attacks. Am. J. Med. Genet. 91:185–189, 2000. © 2000 Wiley-Liss, Inc.

The presence of Campylobacter species other than Campylobacter jejuni and antibodies to Campylobacter concisus in children were investigated. A significantly greater presence of C. concisus and higher levels of antibodies to C. concisus were detected in children with Crohn's disease (CD) than in controls. Campylobacter species other than C. jejuni were isolated from intestinal biopsy specimens of children with CD.

OBJECTIVE—To assess the impact of lifetime continuous care within the John Hunter Hospital cystic fibrosis (CF) clinics on growth and lung function. DESIGN—A cross sectional survey of variables affecting nutritional status in CF was undertaken for 1993 and 1997. Data were retrieved from medical records and grouped into 5 year age bands. MAIN OUTCOME MEASURES—Change in height z-score, weight centile, and forced expiratory volume in one second (FEV1) between patient cohorts receiving specialised care for different lengths of time. RESULTS—Improved mean height z-score (−0.880 v−0.047) and weight centile (28.3% v 48.1%) for the 10-15 year age group in 1997, who had received continuous lifetime care within the clinic, compared with the same age group in 1993, for whom continuous medical care started at an older age. There was no corresponding improvement in FEV1, as an indicator of lung function, in this group (81.6% predicted v 89.5% predicted). CONCLUSIONS—This study suggests that lifetime continuous care within a specialised CF centre is associated with improved growth but not improved lung function.

To evaluate the efficacy of cisapride in the treatment of uncomplicated gastroesophageal reflux in children younger than 36 months of age.A total of 95 patients satisfied the entry criteria and were randomly assigned to double-blind treatment with either cisapride (n = 50), 0.2 mg/kg 4 times daily, or placebo (n = 45) for 2 weeks. At the end of the 2-week treatment period, symptom diary and parental evaluation with repeat 24-hour pH study were performed.Sixty-eight patients completed the trial (38 in the cisapride group and 30 in the placebo group). There were no significant differences in the symptoms of crying, vomiting, or gagging; the overall symptom intensity score; or parental global evaluations. There was a significant difference (P.03) in the percent time pH4, the number of reflux episodes lasting more than 5 minutes, and the duration of the longest episode. No significant difference was demonstrated for the number of episodes with pH4 or the reflux score.Cisapride was no better than placebo for relief of symptoms in children with uncomplicated gastroesophageal reflux. A beneficial effect was demonstrated in the cisapride group in relation to the measured parameters for esophageal acid exposure time.

The high energy requirements in cystic fibrosis (CF) increase the likelihood of malnutrition. Delayed mouth-to-cecum transit times have been reported and raise the possibility that abnormalities of gastric function in CF contribute to reduced food intake. The aims of this project were to document solid-phase gastric emptying times in young people with CF and age- and sex-matched healthy controls, and to investigate whether delayed gastric emptying contributes to suboptimal energy intakes.Nineteen subjects with CF, mean age 12.6 years (11 girls and 8 boys), and 17 control subjects, mean age 12.8 years (9 girls and 8 boys), were studied. Energy intake was assessed by means of a 4-day weighed food record. Fecal fat excretion was determined from a 3-day stool collection. Gastric emptying was assessed with a standard test meal of pancakes labeled with 99mTc-macroalbumin aggregates. The half emptying time of solids from the stomach was recorded.The mean solid-phase gastric emptying time was significantly faster in the CF subjects compared with normal, healthy, age- and sex-matched control subjects (53 min vs. 72.2 min, p0.05). Energy intakes, measured as the percentage of the recommended energy intake for age and sex, were greater in the CF subjects than in the control subjects (115% vs. 89%, p0.01), whereas the mean % FFE for the CF subjects was 9.9%. CF subjects with longer gastric emptying times also had lower relative energy intakes (r = -0.50, p0.05).Gastric emptying time in healthy subjects with CF is rapid. Faster solid-phase gastric emptying times may be secondary to high-fat, high-energy intakes and may represent a survival advantage.

OBJECTIVE To examine general practitioners' (GPs') management of childhood gastroenteritis and their perceptions about barriers to optimal management in the community. DESIGN Cross-sectional postal survey in which GPs' self-reported practices were assessed by a paediatric gastroenterologist for compliance with published guidelines. SETTING Hunter region of NSW, mid 1994. PARTICIPANTS All 422 urban and rural GPs practising in the Hunter region were sent questionnaires; 289 (243 urban and 46 rural) GPs responded. RESULTS Nearly all GPs (97%) recommended clear fluids in the management of childhood gastroenteritis, with 195 (67%) recommending oral electrolyte solution. Management practices were assessed as: optimal, 170 GPs (59%); acceptable, 33 GPs (11%); inappropriate or potentially dangerous, 38 GPs (13%); and too vague to classify, 48 GPs (17%). Multiple logistic regression analysis showed that better management strategies were associated with being younger and practising in rural areas. GPs perceived the main barriers to effective management of gastroenteritis were: inadequate parenting skills, 131 GPs (45%); lack of parental understanding about the illness, 118 GPs (41%); other social problems, 67 GPs (23%); parental anxiety, 57 GPs (20%); and conflicting advice given by others, 42 GPs (15%). Only 33 GPs (11%) identified the taste and 16 (6%) the cost of oral electrolyte solution as major barriers. CONCLUSIONS Most GPs reported management of gastroenteritis was acceptable, although not necessarily optimal. GPs need to ensure that parents fully understand the nature of their child's illness and their recommendations for management at home.

Two studies were conducted to investigate whether vitamin A-deficient rats were more susceptible to intestinal injury caused by methotrexate (MTX), since vitamin A deficiency alone causes only mild changes to jejunal structure and function. Weanling male rats were fed a vitamin A-deficient diet (-VA) for 40-42 d and compared to rats either pair-fed (PF) or with free access (+VA) to the same diet. Drinking water of PF and +VA rats was supplemented with 37.5 microg (Study 1) or 75 microg (Study 2) vitamin A (Rovimix A 500W)/d. Rats in each group received MTX (-VAMTX, PFMTX, +VAMTX) or vehicle. MTX administration reduced intestinal mucosal wet weight, protein and DNA concentrations, and sucrase and maltase activities in -VA and PF rats (P < 0.02). In Study 1, -VAMTX rats developed a severe jejunal enteropathy and had a higher incidence of diarrhea (P < 0.005), greater weight loss (P < 0.005), more disruption of villus architecture (P < 0.0001) and lower disaccharidase activity (P < 0.007) than PFMTX rats. Similar results were observed in Study 2. Liver retinol concentration (but no other variable) was greater in rats receiving 75 microg vitamin A/d (P < 0.001) than in those receiving 37.5 microg/d. The interaction of vitamin A deficiency and small intestinal injury may explain the efficacy of vitamin A supplementation in preventing childhood diarrheal disease mortality in developing countries, and highlights the need for ensuring adequate vitamin A status in people worldwide with diseases and/or treatments which may injure the gastrointestinal tract.

Intestinal permeability can be assessed non-invasively using the lactulose-rhamnose (L-R) test, which is a reliable measure of small intestinal integrity. AIMS To determine risk factors for abnormal intestinal permeability in kwashiorkor, and to measure changes in L-R ratios with inpatient rehabilitation. DESIGN A case-control study of 149 kwashiorkor cases and 45 hospital controls. The L-R test was adapted to study kwashiorkor in Malawi, with testing at weekly intervals during nutritional rehabilitation. Urine sugars were measured by thin layer chromatography in London. RESULTS The initial geometric mean L-R ratios (×100) (with 95% confidence interval) in kwashiorkor were 17.3 (15.0 to 19.8) compared with 7.0 (5.6 to 8.7) for controls. Normal ratios are tropical enteropathy syndrome . Abnormal permeability in kwashiorkor was associated with death, oliguria, sepsis, diarrhoea, wasting and young age. Diarrhoea and death were associated with both decreasedl-rhamnose absorption (diminished absorptive surface area) and increased lactulose permeation (impaired barrier function) whereas nutritional wasting affected only l-rhamnose absorption. Despite clinical recovery, mean L-R ratios improved little on treatment, with mean weekly ratios of 16.3 (14.0 to 19.0), 13.3 (11.1 to 15.9) and 14.4 (11.0 to 18.8). CONCLUSION Abnormal intestinal permeability in kwashiorkor correlates with disease severity, and improves only slowly with nutritional rehabilitation. Key messages Kwashiorkor still has a 30% case fatality rate at urban hospitals in Malawi Intestinal permeability can be measured non-invasively by the lactulose-rhamnose test as an indicator of gut damage The degree of abnormal permeability in kwashiorkor reflects the severity of illness and improves only slowly with nutritional rehabilitation Changes in intestinal permeability can be used to evaluate treatment interventions

An 8-year-old boy presented with first episode of rectal bleeding. Initial hemoglobin was 9 g/dL. A Meckel scan showed a hyperemic focus in the lower pelvis. Colonoscopy identified a juvenile polyp with dysplasia in the rectosigmoid region. It is important to carefully evaluate the dynamic flow images in the Meckel scan because pathology other than a Meckel diverticulum may be identified.

Cyclic AMP-dependent Cl- secretion is the major secretion pathway in human intestine. The aim of the present study was to examine mechanisms involved in cAMP-dependent anion secretion in human small and large intestine. Surgical resection specimens from both jejunum and distal colon were studied under short circuited conditions. Addition of the phosphodiesterase inhibitor IBMX induced an increase in the short-circuit current (Isc) equivalent to the net increase in Cl- secretion. The Isc was inhibited by diphenylamine decarboxylate (DPC; Cl- channel blocker), bumetanide (basolateral Na+/K+/2Cl- cotransporter), BaCl2 (basolateral K+ channel) and Cl- free buffer in both segments and indomethacin (cyclo-oxygenase inhibitor) in colon alone. Diphenylamine decarboxylate appears to directly inhibit secretion in jejunum, although its inhibitory effect is possibly mediated by inhibition of cyclo-oxygenase in the colon. A small component of IBMX-stimulated Isc was inhibited by acetazolamide. Cyclic AMP-dependent secretion is largely apical Cl- secretion, although a small component appears to be HCO3. Secretion is dependent on basolateral K+ channels and Na+/K+/2Cl- cotransporters and, in the colon, is inhibited by indomethacin, implying a role for cyclo-oxygenase metabolites. The chloride channel blocker DPC inhibits secretion in both areas. This class of compounds may have potential for treatment of secretory diarrhoea.

The aim of this study was to measure resting energy expenditure (REE) and energy intake in children with quadriplegic cerebral palsy (CP), to relate these to anthropometric measurements, and to determine the influence of nutritional rehabilitation on REE.Fifty-six children (20 females, 36 males; age range 3y 11mo-18y; mean age 10y; SD 3y 11mo) with CP (Gross Motor Function Classification System level V) participated in this cross-sectional study. Children were excluded if they had a known metabolic disorder, genetic syndrome, or chromosomal abnormality. Thirty-three of the children were tube fed and 23 were fed orally. A comparison group comprised 111 (42 females, 69 males) healthy children who had undergone anthropometric and REE measurements and were of similar age to the children with CP (4-19y). REE was measured by indirect calorimetry and energy intake was determined from weighed food records.The REE in the children with CP was low (79.5%) compared with that predicted and highly variable (SD 38.4%). Fat-free mass was the strongest predictor of REE, accounting for 27% of the variation. Energy intake as a percentage of REE in was greatly overestimated in oral-fed children with CP (293%). In a subset of children with CP (n=14), an increased energy intake by gastrostomy tube feeding resulted in an increase in REE from 70.0% to 101.9% of that predicted.The REE of children with CP is low and variable and is not strongly related to any one anthropometric measurement. Food records in oral-fed children with CP are of little value owing to their inaccuracy. This study provided support for the hypothesis that the low REE found in malnourished children with CP is partly due to a low energy intake.

Background/Aims: Remnant small intestine undergoes adaptation following massive resection. The aim of this study was to examine the effect of epidermal growth factor (EGF) on ileal adaptation following proximal resection. Methods: New Zealand white rabbits, aged 8 weeks, underwent 23 proximal resection, and ileal mucosal adaptation was assessed 10 and 21 days postsurgery. In a second series of experiments, animals with resection received oral EGF (40 μg · kg −1 · day −1 ) for 5 days, and the effect on adaptation was assessed 10 days postsurgery. Results: Transaction alone stimulated mucosal hyperplasia, intestinal sucrase specific activity, and glucose transport at 10 days but not at 21 days. Resection resulted in mucosal hyperplasia at both time periods and increased disaccharidase specific activity at 10 days postresection. In contrast, 3 O -methyl-d-glucose transport was significantly decreased compared with both groups at both time periods. EGF treatment in animals with resection did not alter mucosal proliferation but did stimulate maltase specific activity and caused a 3–4-fold increase in glucose transport and phlorizin binding. Conclusions: Following proximal resection, adaptation of intestinal digestive and absorptive function does not parallel mucosal hyperplasia. Administration of EGF to resected animals enhances glucose absorption and may have a therapeutic role in the management of short gut syndrome.

Background/Aims: Escherichia coli 0157:H7 infection induces diarrhea, severe colitis, and colonic electrolyte transport abnormalities characterized by decreased Na absorption and Cl secretion. The aim of this study was to examine the role of the host inflammatory response in inducing distal colonic transport changes during infection with E. coli 0157:H7. Methods: New Zealand white rabbits aged 10 days were infected with E. coli 0157:H7 strain EDL933 (plasmid + , verotoxin 1 + , verotoxin 2 + ). Studies were performed daily from day 1 to day 5 postinfection and compared with uninfected controls (10 days old). Distal colonic ion transport was studied in vitro under short-circuited conditions in Ussing chambers, and tissue inflammation was assessed by mucosal myeloperoxidase activities and mucosal neutrophil (polymorphonuclear neutrophil [PMN]) counts. In a second study, PMN infiltration was inhibited by an anti-CD18 (leukocyte adhesion molecule) monoclonal antibody, IB 4 , and histology and transport were studied on day 5 postinfection. Results: Infection with 0157:H7 induced diarrhea and inhibition of Na absorption by day 3. Cl secretion occurred on day 5, coincident with tissue infiltration with PMN. Pretreatment with IB 4 prevented histological damage and tissue infiltration with PMN, and it inhibited the transport abnormalities induced by infection alone. Conclusions: Infection with 0157:H7 reduces Na absorption and stimulates Cl secretion in the distal colon. Disruption of the epithelium and changes in colonic electrolyte transport during enterohemorrhagic E. coli are mediated by the host inflammatory response.

Given that members of Helicobacteraceae family colonize the intestinal mucus layer, it has been hypothesized that they may play a role in Crohn's disease. This study investigated the presence of Helicobacteraceae DNA in biopsies collected from children with Crohn's disease and controls.The presence of Helicobacteraceae DNA was investigated in intestinal biopsies collected from 179 children undergoing colonoscopy (Crohn's disease n = 77, controls n = 102) using a Helicobacteraceae-specific PCR.Members of the Helicobacteraceae were detected in 32/77 children with Crohn's disease (41.5%) and 23/102 controls (22.5%). Statistical analysis showed the prevalence of Helicobacteraceae detected in patients to be significantly higher than that in controls (p = .0062). Analysis of non-pylori Helicobacteraceae showed that their prevalence was also significantly higher in patients than in controls (p = .04). Helicobacter pylori was detected in 14.0% of the biopsies across all groups. Given that all children tested were negative for gastric H. pylori, this was a surprising finding. Phylogenetic analysis of H. pylori sequences detected in the biopsies showed that the H. pylori strains identified in the patients did not group with gastric H. pylori included in the analysis, but rather with other H. pylori strains detected in the intestine, gall bladder, and liver.The higher prevalence of Helicobacteraceae DNA in Crohn's disease patients would suggest that members of this family may be involved in this disease. In addition, phylogenetic analysis of H. pylori strains showed that extragastric sequences clustered together, indicating that different H. pylori strains may adapt to colonize extragastric niches.

Orthotopic liver transplantation (OLT) in patients with mitochondrial respiratory chain disorders (MRCD) is controversial because of possible multi-organ involvement.To illustrate the clinical diversity of MRCD, the difficulty in making an accurate tissue diagnosis and whether to undertake OLT in five patients with proven MRCD. A review of the reported cases in the literature is presented.Retrospective chart review from 1995 to 2007 at a paediatric liver transplant centre where five children with hepatic MRCD were identified.Patient 1 was transplanted for 'cryptogenic' cirrhosis. The diagnosis of MRCD was made on the explant. The patient remains well 5 years after transplant. Patient 2 presented with fulminant liver failure at 3 months of age. Although no extrahepatic manifestations were identified, OLT was not considered. Patient 3 presented with recurrent hypoglycaemia and was transplanted for fulminant hepatic failure at 12 months of age. He died of pulmonary hypertension 9 months post OLT. Patient 4 was diagnosed with MRCD at the age of 2 years. Death occurred at the age of 14 years, while listed for combined liver-kidney transplant, after a stroke-like episode following severe sepsis. Patient 5 developed liver failure after valproic acid was instituted for seizures. Mitochondrial DNA depletion syndrome was diagnosed and transplantation was not offered.Hepatic MRCD has a variable presentation. Diagnosis requires the measurement of respiratory chain enzymes on tissue from liver biopsy. Whether to proceed to OLT is a difficult decision given a good outcome in a minority of cases, suggesting that MRCD should not be an absolute contraindication to liver transplantation.

CF liver disease is an uncommon indication for pediatric LT. Determining optimal timing and type (isolated liver versus multi-organ) of transplantation for those with severe liver disease can be challenging and involves consideration of the extent of liver disease (PHT, synthetic dysfunction) and extrahepatic factors such as pulmonary function. We present the experience of isolated LT for CF at our center. Eight children received one allograft each (3.9% of all grafts). One- and four-yr survivals are both 75%. The two deaths occurred within the first two months after LT, and in both cases, invasive fungal infections were implicated, one following treatment for acute severe rejection. All had significant PHT, and six had synthetic dysfunction. All had roux-en Y biliary anastomoses and none developed long-term biliary complications. Seven had pulmonary colonization with Pseudomonas aeruginosa and six with fungus at time of transplantation. Mean pre-LT FEV1 was 80% (range 59-116%) predicted, and lung function post-LT was stable. Isolated LT in children with CF is successful in those with relatively preserved pulmonary function, which does not appear to deteriorate as a consequence. Roux-en Y biliary anastomosis and antifungal prophylaxis should be a part of management of these patients.

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 μ l/cm per 20 min, P ) and Na+ ( 4.0 ± 0.7 versus 2.8 ± 0.9 μ mol/cm per 20 min, P ) absorption ( n = 9 ). In vitro, in Ussing chambers, in both jejunum and ileum, addition of 1.0 μM 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 ( J sm Cl − : jejunum 17.4 ± 1.3 versus 19.8 ± 1.3 μ Eq/cm 2 per h, P , n = 6 ; ileum 13.4 ± 0.5 versus 17.2 ± 0.6 , P , n = 6 ) which was inhibited by the calcium channel antagonist verapamil ( 82 ± 26% , P ) and by the 5-HT2 receptor antagonist cinanserin ( 72 ± 44% , P ). Guanylate cyclase activity was stimulated by ANP in intact epithelium, but not in isolated crypt and villus enterocytes.

The aim of this study was to describe the experience of 452 children and adults with a severe developmental disability who presented to a multidisciplinary clinic with swallowing, nutritional, and gastrointestinal problems. Data were obtained by chart review. Two hundred and ninety-four children (age range 7 mo-19 y, 173 males, 121 females) and 158 adults (age range 18-53 y; 90 males, 68 females) were assessed over 5 years. One hundred and eighty-two children and 86 adults had cerebral palsy. Approximately 90% were wheelchair dependent and totally dependent on caregivers for feeding; 60% had epilepsy. Pulmonary aspiration was identified by oesophageal videofluoroscopy in 41% of 174 children and 47% of 34 adults. Chronic oesophagitis and Helicobacter pylori were found in 57% of 182 children and 76% of 66 adults undergoing endoscopy. Chronic suppurative lung disease was identified by computerized axial tomography in 94% of 62 children and all six adults studied. Most patients improved with simple interventions. However, gastrostomy was recommended in 140 children and performed in 91, and in 10 adults but performed in seven, whereas fundoplication was recommended in 111 children and performed in 74, and in six adults but performed in two. In conclusion, chronic oesophagitis, pulmonary aspiration, and chronic lung disease were identified in many patients with a severe developmental disability.

We report two children who presented with cough and wheeze, were initially misdiagnosed with asthma and were subsequently demonstrated to have achalasia as the underlying cause of their symptoms. These cases highlight the importance of considering diagnoses other than asthma when there is a suboptimal response to asthma medications, as well as the value of investigations including chest X-ray and pulmonary function tests in establishing the underlying cause.

Aim: To describe the findings of paediatric upper gastrointestinal endoscopy (UGE) and to reduce the rate of normal findings in children undergoing diagnostic UGE. Methods: Upper gastrointestinal endoscopy were performed at a single tertiary referral children’s hospital over a 3-year period by four endoscopists. Patients were subgrouped into diagnostic categories (recurrent abdominal pain syndrome (RAP), oesophagitis, coeliac disease and enteropathy/inflammatory bowel disease) and endoscopists recorded their clinical diagnosis as above before each procedure. Endoscopic and biopsy findings were compared with clinical diagnosis. After the first year of audit each endoscopist was appraised of their practice and strategies implemented to reduce the normal UGE. In years 2 and 3 all endoscopists were audited by their peers on a monthly basis. Results: A total of 1172 UGE were performed over a 3-year period. Ninety per cent were diagnostic procedures, of which 48% were normal, 16% identified oesophagitis, 11% coeliac disease, 6% gastritis, 3%Helicobacter pylori and 1% peptic ulcer disease. Peer-review audit significantly reduced the number of normal findings in coeliac disease, RAP and overall (P

Background Rebleeding in the presence of an adequate patent portosystemic shunt in a patient with portal hypertension (PHT) is uncommon. Inferior vena cava (IVC) obstruction as the cause of rebleeding in this situation has not been reported in the literature. Methods Records from a pediatric tertiary care center were reviewed over a 15-year period. Portosystemic shunt procedures for bleeding esophageal varices were done in 39 children. Patients who, after a shunt surgery for PHT, developed a rebleed because of IVC obstruction in the presence of a patent shunt were identified. Results and Conclusions Late IVC obstruction in the presence of a patent shunt was identified in 2 patients. The etiology included adhesions, caudate lobe hypertrophy, and macronodular cirrhosis. Diagnosis was by angiography, and treatment included angioplasty and liver transplantation. Awareness of this condition helps direct treatment appropriately in the clinical scenario of a rebleed in a shunted patient with PHT.

Abetalipoproteinaemia (ABL) and homozygous familial hypobetalipoproteinaemia (FHBL) are rare inherited disorders associated with low or undetectable levels of apolipoprotein B (apoB)-containing lipoproteins. Patients present with the symptoms and sequelae of fat malabsorption, including fat-soluble vitamin deficiencies. We describe two novel mutations: one an APOB gene mutation causing FHBL and the other a microsomal triglyceride transfer protein (MTP) gene mutation causing ABL. Two siblings of consanguineous parents were homozygous for an apoB mutation 4339delT causing an apoB-30.9 truncation. In another family, a boy born to consanguineous parents was homozygous for a 319 bp in-frame deletion of MTP exon 15 (c.2076-39_2303 + 52del319). All three children presented with malabsorption and liver dysfunction and had similar very low serum lipid, apoB, and fat-soluble vitamin levels. The FHBL parents had low serum lipid and apoB profiles distinguishing the disorder from the normal levels in ABL parents. Future patients presenting with FHBL or ABL should be genotyped to provide further insight into the varying clinical severity related to molecular heterogenicity in these two conditions.

Purpose The experience of a single institution on idiopathic fibrosing pancreatitis (IFP) is presented. Methodology This is a retrospective review of medical records of affected patients. Results There were 7 cases with a mean age of 7 years. Upper abdominal pain followed by jaundice was the most common presentation. One child had varicella and 1 developed Crohn's disease 3 years later. In 5 cases, diagnosis was established intraoperatively, whereas 2 cases were diagnosed preoperatively. Ultrasonography suggested the diagnosis in 2 of the 7 cases, contrast computed tomography scan in 1 of the 3 cases, and magnetic resonance cholangiopancreatography in 1 of the 4 cases. Six patients were treated by biliary enteric bypass surgery. Treatment by endoscopic biliary stenting was successful in one. There were no postoperative complications. Pancreatic biopsies showed fibrosis of exocrine elements with preservation of islets. Three patients have pancreatic atrophy, and none has diabetes at follow-up (mean, 62 months). Discussion Idiopathic fibrosing pancreatitis presents as biliary obstruction in children. Precise preoperative diagnosis of IFP is difficult. Noninvasive imaging has limited sensitivity. Surgery offers satisfactory long-term relief of biliary obstruction. Treatment using temporary endoscopic biliary drainage appears promising in treatment of IFP. Patients should be followed up for pancreatic insufficiency, long-term biliary obstruction, and inflammatory bowel disease.

BACKGROUND No studies have directly measured body protein or validated skinfold-thickness anthropometry and dual-energy X-ray absorptiometry (DXA) to assess body protein in children with spastic quadriplegic cerebral palsy (SQCP). OBJECTIVE We aimed to measure and evaluate body protein and to determine whether skinfold-thickness anthropometry and DXA can predict body protein in children with SQCP. DESIGN This was a cross-sectional study of 59 children (22 girls, 37 boys) aged 3.9-19.5 y with SQCP. The children underwent measurements of anthropometric indexes, lean tissue mass by DXA (LTM(DXA)), and total body protein by neutron activation analysis (TBP(NAA)). In addition, TBP was estimated from both skinfold-thickness anthropometry (TBP(SKIN)) and DXA (TBP(DXA)). The agreement of TBP(SKIN) and TBP(DXA) was tested against TBP(NAA) by using Bland and Altman plot analysis. RESULTS Height and weight SD scores (x +/- SD: -3.1 +/- 1.6 and -4.8 +/- 5.3, respectively) were significantly lower than reference data in the children with SQCP (P < 0.001). TBP(NAA) for age and height was low in the children with SQCP (P < 0.001): 56.1 +/- 17.3% and 81.5 +/- 15.7%, respectively, of the values predicted from control data. TBP(SKIN) and TBP(DXA) were both highly correlated with TBP(NAA): r = 0.90, P < 0.001, and r = 0.91, P < 0.001, respectively. Despite these significant correlations, agreement analyses showed wide variation of up to 33.3% of the mean for both methods. CONCLUSIONS Body protein in children with SQCP is significantly reduced for age and height. Skinfold anthropometry and DXA show wide variation in estimation of body protein compared with NAA in this group of children.

The water residence time and diffusional water permeability in colonic epithelial T84 cancer cells was measured using (1)H NMR spectroscopy; the values estimated were 35.2+/-2.8 ms and (7.4+/-0.6)x10(-3)cms(-1), respectively. Water permeability was inhibited to approximately 10% of its original value by the mercurial diuretic, p-chloromercuribenzenesulfonate (PCMBS; 1mM), and fully restored by dithiothreitol (DTT; 1mM). The permeability was also inhibited reversibly to approximately 55%, by extracellular glibenclamide (1mM), an inhibitor of some ATP-binding cassette (ABC) transporters, including the cystic fibrosis transmembrane conductance regulator (CFTR). Addition of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IMBX; 0.1-1mM) and the adenylate cyclase activator, forskolin (0.1-1mM) did not alter water permeability. It is concluded that in T84 cells water diffuses through the membrane lipid bilayer and via channels that are inhibited by PCMBS, including the channels that are known to be inhibited by glibenclamide.

[Extract] The patient, now 9 years of age, was born at 24 weeks gestation. She required artificial ventilation for severe hyaline membrane disease. Her clinical course was complicated by intraventricular haemorrhage, and chronic lung disease. At discharge from the neonatal unit, she was oxygen-dependent and her parents were advised that it was likely that her development would be delayed, and that her life expectancy was ‘guarded’ and she was unlikely to live beyond 3 years.

Colitis is associated with alterations in electrolyte and water transport. These changes give rise to some of the symptoms experienced by patients with colitis. Alterations in fluid flux may also contribute to increased susceptibility to mucosal injury. Recently, endogenous water channel proteins (aquaporins; AQPs), have been identified in colonic tissue. The expression of AQP4, AQP7 and AQP8 was examined, via reverse transcription/polymerase chain reaction, Western blotting and immunohistochemistry, in a murine model of colitis and in patients with inflammatory bowel disease or infectious colitis. Colitis was induced in C57BL/6 mice by the addition of 2.5% dextran sodium sulphate (DSS) to their drinking water. AQP expression in these mice was assessed following 12 h to 7 days of DSS exposure and during the recovery phase from 1 to 15 days following cessation of DSS exposure. Colonic water transport was measured after 1 and 3 days of DSS and following 7 days of recovery. The expression of AQP4 and AQP8 mRNA was significantly decreased after 12-24 h of DSS exposure and remained depressed throughout the treatment period. Expression of AQP7 was more variable. Protein expression followed a similar pattern to that observed for AQP mRNA. Significant alteration in colonic fluid secretion was correlated with reduced expression of AQP isoforms. Significantly, patients with active ulcerative colonic, Crohn's colitis or infectious colitis had similar dramatic reductions in AQP expression that appeared to be correlated with disease activity. Thus, colonic injury in both mouse and man is associated with a downregulation in AQP expression.