The inflammatory milieu and the insulin like growth factor axis in children with inflammatory bowel disease following recombinant human growth hormone treatment.

It is unclear whether recombinant human growth hormone (rhGH) in inflammatory bowel disease (IBD) alters cytokine profile. The objective of this study is to evaluate changes in cytokines and systemic markers of the insulin growth factor axis following 6 months of rhGH treatment in children with IBD. In a six-month randomised control trial in children with IBD treated with rhGH at 0.067 mg/kg/day and controls (11 in each group), we measured pro-, anti-inflammatory cytokines and systemic markers of the IGF axis (total IGF-1, free IGF-1, total IGFBP-3, ALS, IGFBP-2) at baseline (T+0), and six months (T+6). Results expressed as median (range). In the rhGH group, TNFα was 3.1pg/ml (2.9, 100.6) and 3.6pg/ml (3.1, 5.3) at T+0 and T+6, respectively (p=0.85), whereas in the controls this was 3.3pg/ ml (2.7, 4.0) and 3.1pg/m l (2.7, 4.7), respectively (p=0.79). In the rhGH group, IL1ß was 18.0pg/ml (5.0,716.7) and 18.0pg/ml (1.7, 52.2) at T+0 and T+6 respectively(p=0.90), whereas in the controls this was 19.8pg/ml (4.1, 27.1) and 19.1pg/ml (2.4,77.3), respectively (p=0.65). None of the twenty-eight other cytokines analysed was different at T+6 in either group. Despite increase in total IGF1 in the rhGH group (p=0.03), free IGF1, IGFBP3, ALS and IGFBP2 did not change in either group at T+6. Percentage change in IGFBP3, was significantly associated with percentage change in IL2 (r=0.77, p=0.009) and IL4 (r=0.58, p=0.01). Percentage change in ALS was significantly associated with percentage change in IL2 (r=0.90, p less than 0.0001) and IL4 (r=0.63, p=0.04). Although changes in markers of the GH/IGF-1 axis do show an association with cytokines (IL-2, IL-4) in pediatric IBD, six months of rhGH treatment was not associated with any significant changes in levels of a range of pro and anti-inflammatory cytokine. Careful evaluation of disease process is required in future trials of rhGH in paediatric IBD.

Systematic review: the role of tacrolimus in the management of Crohn's disease.

BACKGROUND Several published studies have evaluated the efficacy of tacrolimus in the management of Crohn's disease with variable conclusions. AIM To review systematically the evidence examining the efficacy and safety of tacrolimus in treating Crohn's disease. METHODS The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PUBMED) and EMBASE (1984 to January 2011) were searched. Also, references from selected articles were examined. Case series (five or more patients), cohort and randomised controlled trials were eligible for inclusion, incorporating oral, intravenous or topical tacrolimus therapy. The primary outcome was induction of remission of active Crohn's disease. RESULTS Eleven studies met the inclusion criteria which included 163 patients, of which 127 received tacrolimus therapy. In patients with luminal Crohn's disease, the crude pooled remission rate for tacrolimus was 44.3% (range, 7-69%) and the crude pooled response rate was 37.1% (range, 14-57%). For patients with perianal disease using systemic tacrolimus, crude pooled remission rate was 28.6% (range, 0-64%) and crude pooled response rate was 38.8% (range, 0-57%). Combining data from two studies using topical tacrolimus, 35.7% of patients achieved remission and 28.6% partial response. Nonserious adverse effects are common, particularly tremor, paraesthesia and headache. Reversible nephrotoxity occurred in 16% of patients. CONCLUSIONS The current evidence; although of a poor quality, appears to support the use of tacrolimus in Crohn's disease. High quality randomised controlled trials are needed.

A preliminary trial of the effect of recombinant human growth hormone on short-term linear growth and glucose homeostasis in children with Crohn's disease.

BACKGROUND: It is unclear whether recombinant human growth hormone (rhGH) improves linear growth in children with Crohn's disease (CD). AIMS: To investigate the effects of rhGH on height velocity (HV) and glucose homeostasis over a 6-month period. DESIGN AND SETTING: Randomized controlled trial in two tertiary children's hospitals in 22 children with inflammatory bowel disease amongst whom 21 had CD. Duration of disease from diagnosis and number of acute relapses requiring either exclusive enteral nutrition or therapeutic dose of oral prednisolone were similar in the treatment and control groups. INTERVENTION: Either rhGH (0·067 mg/kg per day) as daily subcutaneous injections (rhGH group; n, 11) or no rhGH, (Ctrl; n, 11) for 6 months. MAIN OUTCOME MEASURE: Percentage change in HV after 6 months in the two groups. Auxology, puberty, skeletal age, disease factors, treatment and glucose homeostasis were also assessed. RESULTS: Median HV increased from 4·5 (range, 0·6, 8·9) at baseline to 10·8 (6·1, 15·0) cm/year at 6 month (P = 0·003) in the rhGH group, whereas in the Ctrl group, it was 3·8 (1·4, 6·7) and 3·5 cm/year (2·0, 9·6), respectively (P = 0·58). Median percentage increase in HV after 6 months in the rhGH group was 140% (16·7, 916·7) compared with 17·4% (-42·1%, 97·7%) in the Ctrl group (P < 0·001). There were no significant differences in disease activity and proinflammatory cytokines at baseline and 6 months in both groups and change in bone age for chronological age was also similar in the two groups. In the rhGH group, fasting insulin increased from 4·0 (2·0, 11·0) to 7·0 mU/l (2·0, 16·0) (P = 0·02), whereas in the Ctrl group, it was 3·0 (1·2, 12·7) and 3·8 mU/l (2·1, 7·0) (P = 0·72), respectively. CONCLUSIONS: Although this pilot trial shows that rhGH can improve short-term linear growth in children with CD, the clinical efficacy of this therapy needs to be further studied in longer-term studies of growth, glucose homeostasis and disease status.

Traction removal of percutaneous endoscopic gastrostomy devices in children.

BACKGROUND: There are few published data on non-endoscopic removal of percutaneous endoscopic gastrostomy devices in children. AIMS: To describe prospective data acquired for traction removal of percutaneous endoscopic gastrostomy devices at a single pediatric center over a 5-year period. METHODS: Data were obtained from endoscopy records, computerized hospital patient information systems and case note analysis. The device that could be removed by traction was the Corflo (Merck) 12-Fr percutaneous endoscopic gastrostomy tube with a collapsible internal retention dome. All procedures were performed under general anesthesia. RESULTS: Between 2002-2006, 220 children underwent percutaneous endoscopic gastrostomy removals (166 by traction, 51 endoscopically and 3 Foley catheter to button conversions). The median duration between percutaneous endoscopic gastrostomy insertion and low profile button device substitution was 0.83 years (0.12-3.86). Complications from traction removal included internal retention dome separation in two cases (allowed to pass per rectum, uneventfully), failure to a insert a low profile button device needing percutaneous endoscopic gastrostomy reinsertion, enterocutaneous fistula requiring surgical closure in one patient and laparoscopy for suspected low profile button device misplacement in one instance. The material cost of endoscope disinfection (£10) and disposable usage (£80) avoided by traction removal was calculated at £90 per procedure. CONCLUSION: No mortality occurred as a result of the traction removal of percutaneous endoscopic gastrostomy tubes. Laparoscopy for suspected low profile button device misplacement was needed in one case (0.60%). Traction removal of percutaneous endoscopic gastrostomy tubes was generally safe and a cost-saving procedure in our experience.

Central venous catheter infection with Bacillus pumilus in an immunocompetent child: a case report.

BACKGROUND: Bacillus organisms are common laboratory contaminants. The majority of Bacillus bacteraemias are transient and not clinically significant. Clinically significant infection due to Bacillus species is rare and mostly due to Bacillus cereus infections in immuno-compromised hosts. CASE PRESENTATION: We report a case of central venous catheter infection with Bacillus pumilus in an immunocompetent child with tufting enteropathy on long-term parenteral nutrition (PN). There were three episodes of central venous catheter infection with Bacillus pumilus in three months. Despite adequate and appropriate use of intravenous antibiotics, the infection failed to clear resulting in the need for removal of the catheter for complete cure. CONCLUSION: Bacillus species can cause clinically significant central venous catheter infection, even in an immunocompetent host. Despite adequate antibiotic treatment, the central venous catheter may need removal for complete cure.

Surgical management of inflammatory bowel disease.

AIM: To evaluate the outcome and morbidity after major surgical interventions for inflammatory bowel disease (IBD). METHODS: Retrospective case note analysis of 227 children referred to a tertiary referral centre between 1994 and 2002 for treatment of IBD. RESULTS: 26 of 125 children with Crohn's disease (21%) required surgical management. 13 with disease proximal to the left colon underwent limited segmental resections and primary anastomosis, without significant morbidity. Primary surgery for 13 children with disease distal to the transverse colon included 6 subtotal-colectomies or panprocto-colectomies. All seven children undergoing conservative segmental resections (three with primary anastomosis, four with stoma formation), required further colonic resection or defunctioning stoma formation. All three children undergoing primary anastomosis developed a leak or fistula formation. 22 of 102 children with ulcerative colitis (22%) required surgery. Definitive procedures (n = 17) included J-pouch ileoanal anastomosis (n = 11), ileorectal anastomosis (n = 2), straight ileoanal anastomosis (n = 3), and proctectomy/ileostomy (n = 1). Five children await restorative surgery after subtotal colectomy. Median daily stool frequency after J-pouch surgery was 5 (range 3-15), and 10 of 11 children reported full daytime continence. All three children with straight ileoanal anastomosis had unacceptable stool frequency and remain diverted. CONCLUSION: The complication rate after resectional surgery for IBD was 57% for Crohn's disease, and 31% for ulcerative colitis. In children with Crohn's disease, limited resection with primary anastomosis is safe proximal to the left colon. Where surgery is indicated for disease distal to the transverse colon, subtotal or panproctocolectomy is indicated, and an anastomosis should be avoided. Children with ulcerative colitis had a good functional outcome after J-pouch reconstruction. However, the overall failure rate of attempted reconstructive surgery was 24%, largely owing to the poor results of straight ileoanal anastomosis.

Lack of inhibitory effect of cimetidine on caffeine metabolism in children using the caffeine breath test.

AIMS: To study the potential drug interaction between cimetidine and caffeine in a group of children who received cimetidine for gastritis. METHODS: The caffeine breath test was carried out prior to the administration of cimetidine and after 2-3 weeks therapy. The children (n = 1) received 300-800 mg cimetidine daily (11-36 mg kg(-1) day(-1)). RESULTS: There was no significant change in the 2 h cumulative labelled CO2 following the administration of cimetidine (mean values 5.61% before and 4.87% during cimetidine; Student's t-test P > 0.2). CONCLUSIONS: Cimetidine did not have an inhibitory effect on the metabolism of caffeine in this group of children studied.

Helicobacter pylori infection in children: relation with current household living conditions.

BACKGROUND: Studies demonstrating that deprived household living conditions during childhood are risk factors for acquisition of Helicobacter pylori infection have been performed mainly in adults, who probably acquired the infection several decades ago. This study investigates whether deprived household living conditions remain important risk factors for infection in subjects (children) with recently acquired infection. AIMS: To examine the relation between current household living conditions and acquisition of H pylori infection in childhood. SUBJECTS/SETTING: Opportunistically recruited group of 367 children, aged 3 to 15 years, undergoing routine non-gastrointestinal day surgery. METHODS: Anti-H pylori IgG antibodies measured by a commercial enzyme linked immunosorbent assay validated for use in children. Postal questionnaire collecting sociodemographic data and data on household living conditions. RESULTS: Infection was associated with social class and overcrowding in the household. After adjustment for age, social class, and household density, a positive association remained between infection with H pylori and bed-sharing between children and parents on one or two nights per week, odds ratio for infection (95% CI), 2.29 (1.21, 4.32) or more frequently, odds ratio for infection (95% CI), 2.95 (1.35, 6.45). CONCLUSIONS: The continuing importance of household living conditions in the acquisition of H pylori infection is confirmed and household crowding and sharing a bed with a parent are identified as risk factors for infection.

Esophageal stricture in children: fiber-optic endoscopy and dilatation under fluoroscopic control.

We made a retrospective analysis of the efficacy and complication rate of 268 esophageal dilatation procedures performed under fluoroscopic control using the fiber-optic endoscope in 45 children with esophageal stricture. Antegrade and retrograde stricture dilatation was performed under general anesthetic, mainly as an outpatient procedure. Thirty-six children had an esophageal stricture following tracheoesophageal fistula and/or esophageal atresia repair, and nine children had severe corrosive stricture of the esophagus following lye ingestion. The procedure was well tolerated and effective.

Nutritional rehabilitation in cystic fibrosis: a 5 year follow-up study.

Previously, we reported catch-up weight gain, growth, and improved lung function in a group of malnourished cystic fibrosis (CF) children receiving aggressive nutritional supplementation for 1 year compared with a forced expiratory volume in 1 s (FEV1)-, height-, and sex-matched comparison group receiving standard therapy. To evaluate long-term effects, the clinical progress of both groups has been studied over a 5 year period. The supplemented group (n = 10) received supplements for a median of 1.35 years to achieve nutritional rehabilitation. Compared with the nonsupplemented group (n = 14), the previously supplemented group had lower mortality (2 vs. 4, N.S.) and significantly greater weight and height z scores at 4 and 5 years. The progression of pulmonary function abnormalities as measured by FEV1 and forced vital capacity (FVC) slopes was greater at 3 years in the nonsupplemented group (FEV1, p less than 0.05) but no significant differences in rates of deterioration of pulmonary function were seen after 5 years in the two groups of survivors. We conclude that intensive nutritional support for 1 year has both short- and long-term effects on nutrition and growth, still evident some years after the cessation of this therapeutic modality. Supplementation for periods of longer than 1 year may produce greater gains and possibly prolong the improvement in pulmonary function observed in the earlier study.

Treatment of refractory ulcerative oesophagitis with omeprazole.

A 7 year old boy with ulcerative oesophagitis failed to respond to a two month course of intensive medical treatment using H2 receptor antagonist treatment in combination with domperidone and sucralfate. He demonstrated complete resolution using omeprazole 10 mg once a day for eight weeks.

Ceftazidime treatment in cystic fibrosis: resistant organisms in sputum and faeces.

Ceftazidime was used as the only intravenous agent for treating lower respiratory tract infections in patients with cystic fibrosis. The risks of inducing beta lactamases and conferring antibiotic resistance are high when monotherapy is used; so the emergence of resistant bacteria was studied prospectively in the sputum of 120 patients. The mean age of patients was 9.0 (range 0.3-25) years and there were equal number of male and female patients. Pseudomonas aeruginosa was the only ceftazidime resistant bacterium to be isolated from the respiratory tract, and was identified only in chronically colonised patients. Ceftazidime resistance occurred in 103 (14%) of 750 P aeruginosa isolates, and in 16 of 36 chronically colonised patients. Ceftazidime resistant organisms were isolated from the faeces of 17 of 64 patients investigated. Eighty two per cent of the resistant faecal organisms were single isolates: the same resistant organism in faeces was isolated from successive samples in only two patients. In no case was the ceftazidime resistant enteric isolate the same as that from sputum. Patients chronically colonised by P aeruginosa did not harbour ceftazidime resistant enteric organisms any more than non-colonised patients. The use of ceftazidime as a single intravenous agent in treating chest exacerbations in cystic fibrosis does not induce a reservoir of ceftazidime resistant bacteria.

Cystic fibrosis, Pseudomonas aeruginosa, and selective decontamination.

We used an oral topical antibiotic preparation to try and prevent oropharyngeal carriage of Pseudomonas aeruginosa in patients with cystic fibrosis. Ten of 15 patients treated with a two week course of intravenous ceftazidime together with a 90 day course of an antibiotic containing gel continued to carry P aeruginosa in the oropharynx.

Fluorescein dilaurate test of exocrine pancreatic function in cystic fibrosis.

The fluorescein dilaurate test, a non-invasive test of exocrine pancreatic function, was carried out on 21 children with cystic fibrosis and pancreatic exocrine insufficiency, and 12 healthy siblings. The test clearly discriminated between the patients with cystic fibrosis and severe exocrine pancreatic insufficiency and the normal control subjects.

Small intestinal permeability and orocaecal transit time in cystic fibrosis.

Cellobiose and mannitol were used as probe molecules to measure intestinal permeability in 36 children with cystic fibrosis, and 25 age matched controls. Orocaecal transit was also evaluated for each subject using the lactulose/hydrogen breath test. There was a fourfold increase in permeability to disaccharide (cellobiose) in patients with cystic fibrosis, but permeability to the monosaccharide (mannitol) was similar to controls. The orocaecal transit time of lactulose was prolonged in patients with cystic fibrosis, but was unrelated to the percentage excretion of cellobiose or mannitol in cystic fibrosis patients or control subjects.

Pathology mimicking distal intestinal obstruction syndrome in cystic fibrosis.

Eight patients with cystic fibrosis had chronic abdominal pain and the other features of distal intestinal obstruction syndrome. Coexistent abdominal pathology was shown in six patients. Two had a small bowel volvulus, and the others had Crohn's disease, a small bowel fistula, appendix abscess, and an ovarian dermoid. Opiate abuse exacerbated symptoms in two other patients.