[Efficacy, tolerance and safety of polyethylene glycol 3350 plus electrolytes for the treatment of functional constipation in children]. / Eficacia, tolerancia y seguridad a largo plazo del polietilenglicol 3350 con electrolitos en el tratamiento del estreñimiento funcional en niños.

OBJECTIVE: To assess the renal safety of treatment with polyethylene glycol 3350 with electrolytes at 1, 3 and 6 months, its gastrointestinal tolerance and dose effectiveness. PATIENTS AND METHODS: Three groups of 30 healthy patient aged 2-10 years (mean 6.2 years) who suffered functional constipation (Rome III criteria) with 1, 3 and 6 months of treatment were evaluated. Efficacy was evaluated by the change in the number of stools per week and stool consistency (Bristol scale). Urine screens, sodium and osmolality, were performed at the beginning and after 1, 3 and 6 months of treatment. Stool sample NIRA (near-infrared reflectance analysis) and hydrogen breath test analysis samples were performed on the one-month treatment group. RESULTS: The mean dose was 0.37g/kg/day (range 0.18 to 0.8) titrated according to age, weight and response. The number of stools per week during treatment (2.4±0.64) showed a significant difference (P<.001) vs (6.21±1.5) after treatment. There was also a significant difference in the Bristol scale score (1.9±0.75 vs 4.9±1.1 [P<.001]). The mean sodium intake was 112mg (5mg/kg/day [range 4-12mg/kg/day]). The values of sodium and urine osmolality were normal in all groups with no statistical difference compared to normal control values (90 healthy children without treatment). NIRA values were normal in all patients. The hydrogen breath test was normal with a median of 7ppm. CONCLUSION: There were no adverse renal biochemical parameters or gastrointestinal disorders. Tolerance and efficacy was shown to be optimal. Polyethylene glycol 3350 with electrolytes can be safely recommended for the treatment of functional constipation in children in the short and long term.

[MRI enterography in the assessment of paediatric Crohn's disease]. / Utilidad de la entero-resonancia magnética en el estudio de la enfermedad de Crohn pediátrica.

OBJECTIVE: To determine the usefulness of MRI enterography for assessing the extension and activity of paediatric Crohn's disease. MRI findings were compared with clinical, biological, endoscopic and other imaging data. PATIENTS AND METHODS: Studies of MRI enterography use in patients younger than 18 years of age were reviewed. Patients received 500-1000mL of polyethylene glycol one hour before examination (1.5-TMR). T2 HASTE sequences with or without fat saturation, T2 true-FISP, T1 with fat saturation, pre- and post gadolinium-enhanced VIBE sequences, and dynamic and diffusion HASTE were acquired. Thickening of the bowel wall, mucosal enhancement, and extra-luminal complications were evaluated. Five MRI patterns (normal, fibrosis, mild, moderate, and severe transmural activity) were defined. Findings were compared with PCDAI scores, inflammatory parameters, and endoscopic and histological results. RESULTS: Twenty-two studies were reviewed. Optimal intestinal distension was present in 82% of the cases. Mild side effects were observed in 12% of patients. There was a significant relationship between MRI patterns and PCDAI scores (P=.002), sedimentation rate (P=.006) and serum PCR levels (P=.047) and a non-significant relationship with the histology (P=.571). MRI enterography correctly assessed the ileal (80%) and colonic (66%) extension. Extra-luminal complications unrelated to MRI classification (P=.274) were reported in 86.4% of studies. CONCLUSIONS: There was a significant relationship between MRI patterns and PCR, sedimentation rate, and PCDAI scores. MRI enterography showed excellent agreement with ileoscopies, and allowed endoscopically non-accessible areas to be assessed, as well as the diagnosis of extra-luminal complications without irradiation.

[Safety and efficacy of polyethylene glycol 3350 plus electrolytes for the treatment of functional constipation in children]. / Seguridad y eficacia del polietilenglicol 3350 con electrolitos en el tratamiento del estreñimiento funcional en niños.

INTRODUCTION: Polyethylene glycol 3350 plus electrolytes (PEG+E) efficacy has been validated in some studies, but not many have evaluated its safety in children. The aim of our study was to evaluate the safety; renal, malabsorption or excessive production of gas and efficacy of PEG+E treatment in our paediatric population. PATIENTS AND METHODS: Fifteen patients who suffered functional constipation (Rome III criteria) were evaluated. Median age was 6.2 years (r 2-9). All patients had normal renal function. PEG+E were administered for 4 weeks (4WP). The mean dose was 0.44 g/kg/day, titrated according to age, weight and response. Urine screens (sodium and osmolality) were performed at the beginning and 4WP. Stool sample NIRA (near-infrared reflectance analysis) and hydrogen breath test analysis samples were performed at 4WP. To analyse the efficacy of the treatment, the number of stools per week and stool form type (Bristol stool scale) were recorded. RESULTS: The number of stools per week was higher after 4 weeks (2.46 ± 0.71 vs 5.29 ± 1.68, P<.001), as well as the stool form score (2.47 ± 1.24 vs 4.5 ± 0.91, P<.001). No statistical differences were obtained between urine sodium and urine osmolality values at the beginning and 4WP. After 4WP the NIRA median values were normal in all patients [fat 4.45% (range (r) 3.6-7.09); nitrogen 0.78% (r 0.4-1); sugars 1.4% (r 0.47-2.35) and water 68% (r 59-74)]. Median breath hydrogen test was 7 ppm (r 2-18). CONCLUSIONS: No adverse effects on biochemistry values or gastrointestinal disturbances were observed. PEG+E can be recommended for the treatment of functional constipation in children.

[Thickened infant formula, rheological study of the "in vitro" properties]. / Estudio del comportamiento reológico in vitro de las fórmulas antirregurgitación.

INTRODUCTION: Thickened infant formulas, specially formulated to increase the viscosity, are commonly used in the treatment of regurgitation in the non-complicated gastroesophageal reflux. OBJECTIVE: To analyse viscosity and the rheological behaviour of different thickened standard formulas on the Spanish market compared to a standard formula with or without the addition of 10 g/100mL of gluten-free cereals. METHODS: Viscosity of the samples was evaluated in a Bohlim CS-1o controlled-stress rheometer and was performed at basal conditions (25 degrees C, pH 7) and at simulated gastric conditions (37 degrees C, pH 4 and 10 g/100mL of pepsin) at time 0, 30 and after 60 min of incubation. Values were expressed as centipoises (cp) (1 cp=1/100 p). RESULTS: All formulas show a viscosity increase both in basal conditions and in gastric simulated conditions but the behaviour is very heterogeneous. Formulas containing bean gum (carob seed flour) with 2.9 g/100g and a protein ratio similar to cow's milk (80 casein/20 whey) showed the highest and consistent viscosity (70 cp and 90 cp), with significant differences compared to the standard formula in all the measurements. When this thickener is in formulas with a protein ratio similar to breast milk (40 casein/60 whey) the viscosity was lower and reached 50 cp only with the thickener at a concentration of 4.7 gr/100g, achieving significant differences versus standard formula. The formulas with starch thickeners (rice, potatoes and corn) achieved a lower and less consistent viscosity, with no significant difference. The viscosity reached after the addition of cereals both in basal conditions and in gastric simulated conditions was similar to that achieved with more effective thickeners. Lipid concentration is not involved in viscosity and rheological behaviour. CONCLUSION: The viscosity of the thickened infant formula depends on the agent used, concentration and protein ratio. Not all reach a viscosity of 50 cp, hypothetical value to reach, since it doubles the viscosity of a standard formula. The ideal viscosity to be reached and the role of other components of the formula in the viscosity and rheological behaviour is still unclear.

[Optimising azathioprine treatment: determination of thiopurine methyltransferase activity and thiopurine metabolites]. / Optimización del tratamiento con azatioprina: determinación de la actividad de tiopurina metiltransferasa y las concentraciones de metabolitos tiopurínicos.

INTRODUCTION: Individualised doses of azathioprine (AZA) may be prescribed by monitoring the levels of the enzyme thiopurine methyltransferase (TPMT). The measurements of thiopurine metabolites of AZA, 6-thioguanine (6-TGN) and 6-methylmercaptopurine (6-MMP), have also been reported as new markers of AZA activity. OBJECTIVES: To describe TPMT phenotype in our population and to establish a relationship between thiopurine metabolites,and therapeutic activity and adverse effects. MATERIAL AND METHODS: Data on TPMT were retrospectively collected from 107 patients, and 6-TGN and 6-MMP levels in 18 patients currently on treatment with AZA (Crohn's disease 5, ulcerative colitis 5, autoimmune hepatitis 5). RESULTS: Mean value of TPMT was 20.19U/ml. None of the patients had a TPMT activity<5U/ml. Of the 18 patients on treatment, 13 showed sub-therapeutic levels of 6-TGN (<235pmol/8x10(8) red blood cells). Clinical remission was maintained in 45% of patients. Mean levels of 6-TGN in patients with clinical remission were 259pmol/8x10(8) red blood cells versus 209pmol/8x10(8) red blood cells in non-responders (p=0.37). There was an inverse relationship (r=-0.28) between TPMT and 6-TGN levels. Toxic effects occurred in 6 of 18 patients, with leukopenia in 5 and hyperamylasemia in 1. CONCLUSIONS: Determination of TPMT and monitoring of thiopurine metabolites allows AZA treatment to be optimised, although further studies are necessary to establish therapeutic effectiveness and toxicity ranges.

Prevalence and dietetic management of mild gastrointestinal disorders in milk-fed infants.

AIM: To assess the prevalence of mild gastrointestinal disorders in milk-fed infants in paediatric practice, and to evaluate the effectiveness and satisfaction with dietetic treatment. METHODS: A cross-sectional epidemiological study was first carried out. A total of 285 paediatricians included 3487 children seen during a period of one week. In a second phase an observational, prospective and multicentre study was conducted and 2069 milk-fed infants with mild gastrointestinal disorders (colic, constipation, regurgitation and diarrhoea) were included. There was a baseline visit (start of treatment) and a final visit four weeks later. The effectiveness of the various Novalac formulas, as well as the satisfaction of the parents/tutors and paediatricians with the dietetic treatment were assessed at the final visit. RESULTS: The prevalence of mild gastrointestinal disorders was 27.8% of all paediatrician consultations (9.2%, 7.8%, 6.1% and 4.6% in relation to colic, constipation, regurgitation and diarrhoea, respectively). The several Novalac adapted milk formulas resolved 88.4% of the mild gastrointestinal disorders. Depending on the type of disorder, differences in response rate were observed. The highest effectiveness was recorded with respect to diarrhoea (92.6%), followed by constipation (91.6%), colic (87.6%) and regurgitation (81%). Overall, 91% of the paediatricians and 88.8% of the parents/tutors were satisfied or very satisfied with the Novalac adapted milk formulas. CONCLUSION: Mild gastrointestinal disorders show a high prevalence in paediatric practice. The Novalac adapted milk formulas have been shown to be effective in treating mild gastrointestinal disorders in milk-fed infants in the context of routine clinical practice.

[Macroamylasaemia in paediatrics]. / Macroamilasemia en pediatría.

Macroamylasaemia should be considered in any patient with high plasma amylase, no clinical signs and negative additional investigations for pancreatic or parotid diseases. It is characterised by an increase in serum amylase due to circulating high molecular mass macrocomplexes, most often formed due the binding of the amylase to an immunoglobulin. With a normal renal function, a hyperamylasaemia without an increase in urine amylase suggests the diagnosis, and is confirmed by identifying the macromolecular components. It is an uncommon entity in paediatrics. It has been described as a casual finding associated to abdominal pain and to celiac disease. We report two paediatric cases of macroamylasaemia, and a review of the tests needed for its diagnosis. The better understanding of this biochemical anomaly allows us to differentiate it from other situations associated to hyperamylasaemia, in order to avoid additional invasive explorations and unnecessary treatments.

[Improvement of intestinal function in cystic fibrosis patients using probiotics]. / Optimización de la función intestinal en pacientes con fibrosis quística mediante la administración de probióticos.

INTRODUCTION: In some cases, cystic fibrosis may include intestinal inflammation and bacterial overgrowth. Probiotics are considered as immunomodulatory, anti-inflammatory and microbiotic regulator substances. The aim of our study is to determine the prevalence of bacterial overgrowth in cystic fibrosis patients and try to improve the intestinal function with the administration of probiotics. PATIENTS AND METHOD: We examined 20 patients with cystic fibrosis (mean age 10.33, range 5 to 17 years). The expired hydrogen test with a 2 g/kg of 20% dextrose overload was performed on 10 patients. After the test, Lactobacillus rhamnosus LGG 10(11) CFU was administered twice daily for four weeks. Faecal near infrared spectroscopy (FENIR) of water, fat, nitrogen and sugar content in faeces was performed before and after probiotics administration. RESULTS: Five patients (50%) showed bacterial overgrowth. We obtained a positive correlation between the hydrogen test and steatorrhea (R = 0.57) and sugar in faeces (R = 0.52). The FENIR results pre-treatment vs post-treatment were: fat 6.2 g +/- 3.3 g vs. 4.9 g +/- 2.1 g (p < 0.05), sugar 6.7 +/- g 3.6 g vs. 5 g +/- 2.6 g (p < 0.05) and nitrogen 0.87 g +/- 0.27 g vs. 0.91 g +/- 0.14 g (NS) respectively. Thirteen patients (81.25%) had improved stool appearance and intestinal comfort and nine (56.25%) decreased the number of daily stools. CONCLUSIONS: Probiotics improved not only clinical but also biochemical intestinal function in cystic fibrosis patients. These could be given as a regular treatment in this type of patients and in those with bacterial overgrowth.

[Infliximab therapy for inflammatory bowel disease: seven years on]. / Tratamiento de la enfermedad inflamatoria intestinal con infliximab: 7 años de experiencia.

INTRODUCTION: The aim of this study was to describe the clinical experience of our center of the use of infliximab in pediatric patients with inflammatory bowel disease. MATERIAL AND METHODS: We retrospectively reviewed all infliximab infusions administered in the Pediatric Gastroenterology Unit from October of 1999 to October of 2006. Fourteen patients (nine with Crohn's disease, three with ulcerative colitis, and two with indeterminate colitis) with a mean age of 9.6 years at diagnosis were treated with infliximab. Seventy-seven infusions were administered. RESULTS: Efficacy was analyzed according to inflammatory bowel disease. Crohn's disease: in severe cases (PCDAI > 30), clinical remission (PCDAI < 10) was obtained in 80 % of the patients at week 10, decreasing to 60 % at week 54. Corticosteroid therapy could be reduced in 89 % of the patients and was discontinued in 55.5 %. Ulcerative colitis: clinical remission (modified Truelove-Witts index < 10) was initially obtained in 100 % of the patients but only 33 % were still in clinical remission at the end of the study. In the two corticosteroid-dependent patients, corticosteroid therapy could be reduced and even discontinued in one (50 %). Indeterminate colitis: neither of the two patients achieved clinical remission. The most frequent adverse effects observed were acute infusional reactions (42.8 % of the patients and 10.3 % of infusions), one of which was severe, and infections (28.6 % of patients), one of which (ileal abscess) required surgery. CONCLUSIONS: The efficacy of infliximab seems to differ considerably in the distinct types of inflammatory bowel disease and is practically null in indeterminate colitis. Randomized controlled studies in children are required to assess the exact efficacy of infliximab in our patients.

[Intake of fermented milk containing Lactobacillus casei DN-114 001 and its effect on gut flora]. / Efecto de la ingesta de leche fermentada con Lactobacillus casei DN-114 001 sobre la flora intestinal.

OBJECTIVE: To study the gut flora in infants who received fermented milk containing Lactobacillus casei and Streptococcus termophilus and its effect on secretory immunoglobulin levels. MATERIAL AND METHODS: An experimental, randomized, prospective, parallel group study was carried out. Thirty-five infants were included (18 in the treatment group and 17 in the control group) with a mean age of 2 years (SD: 0.6 years; range: 1-3 years). The experimental group received both fermented milk (0.5 l/day) containing L. casei and S. termophilus for 6 weeks and standard cow's milk for the following 6 weeks. The control group received standard cow's milk (0.5 l/day) for 12 weeks. Secretory IgA levels in saliva were evaluated in the experimental group at the start of the study (baseline levels) and 6 weeks later. In both groups, stools were collected to study gut flora at 0, 6 and 12 week. RESULTS: Secretory IgA levels significantly increased (p =0.0063) from a mean baseline value of 2.5 mg/dl to a mean of 3.4 mg/dl at 6 weeks. Gram-negative aerobic flora were decreased in the experimental group after 6 weeks compared with the control group (p =0.0203). The number of infants with Lactobacillus spp in their gut flora was greater in the experimental group than in the control group at week 6 and this difference was statistically significant (p =0.028) at week 12. Conclusion The present study provides evidence of L. casei survival in the gastrointestinal tract and of its effect of increasing secretory IgA.

[Use of goat's milk in patients with cow's milk allergy]. / Empleo de leche de cabra en pacientes con alergia a las proteínas de la leche de vaca.

BACKGROUND: Several epidemiological studies estimate that cow's milk allergy affects approximately 3-5 % of infants in industrialized countries. Infant formulae based on soy protein or hydrolysates free of cow's milk protein guarantee adequate nutritional development, although they may be inadequate for older patients. OBJECTIVE: To evaluate the possibility of using goat's milk in these patients by investigating possible cross-reactivity between both proteins in vivo and in vitro. METHODS: Twelve patients with cow's milk allergy were tested for tolerance to goat's milk protein through radioallergosorbent assay (RAST), specific IgE, skin prick and challenge tests. RESULTS: Only 25 % of the patients showed adequate immediate and late oral tolerance and had negative results of immunological tests for adverse reactions. CONCLUSIONS: The use of goat's milk cannot be recommended to patients with cow's milk allergy without investigation of possible tolerance by a specialist. For the 25 % of patients that tolerate goat's protein, goat's milk can be a excellent substitute in children older than 2 years old.

The influence of dietary palmitic acid triacylglyceride position on the fatty acid, calcium and magnesium contents of at term newborn faeces.

The distribution of long-chain saturated fatty acids in triglycerides is different in infant formulas to that in human milk. In human milk, palmitic acid is predominantly esterified in the sn-2 position (beta-position) of the triglycerides, whereas in infant formulas, it is esterified mainly in the sn-1,3 positions (alpha,alpha'-positions). The specific distribution of the fatty acids in the triglyceride plays a key role in lipid digestion and absorption. We studied fatty-acid, calcium and magnesium composition in the faeces of three groups of at term newborn infants fed different diets: Group A (n=12) was fed from birth to 2 months with human milk (66% palmitic acid in beta-position), Group B (n=12) was fed with formula alpha (19% palmitic acid esterified in beta-position) for 2 months, and Group C (n=12) was fed with formula alpha during the first month and with formula beta (44.5% palmitic acid in beta-position) during the second month. Samples were taken at the end of the first month (t0) and at the end of the second month (t1). Groups A and C presented significantly lower contents of palmitic acid in faeces at t1 than at t0, whereas in Group B, amounts remained similar. Faecal calcium in Groups A and C decreased in the second month (t1), although the fall was no statistically significant. In Group B, calcium amounts showed no change. We found that infant formula beta when compared with infant formula alpha reduced significantly the contents of total fatty acids and palmitic acid in faeces. We conclude that palmitic acid in beta-position is, therefore, beneficial for term infants.

[The response of the hepatitis C and hepatitis G viruses to treatment with recombinant interferon alfa-2b]. / Respuesta del virus de la hepatitis C y del virus de la hepatitis G al tratamiento con interferon alfa-2b recombinante.

OBJECTIVE: The efficacy of recombinant alfa-2b interferon therapy in C-virus (HCV) and G-virus (HGV) in children with chronic hepatitis C was evaluated. PATIENTS AND METHODS: Fifteen patients, between 6 and 16 years of age and positive for HCV of which four were also infected with HGV, were treated with interferon (3 M three times a week for 6 months). The responders were treated for 12 months. HCV RNA, antibodies to HCV, HVC viral genome (expressed as 1000 copy equivalents of HCV genome = 1 keq), HGV RNA (RT/PCR, 5'NCR-NS5), and E2-HGV antibodies were determined before treatment and at 3 and 6 months in all patients and at 12-24 months in the responders. RESULTS: Four HCV patients (27%) with low viral load (mean 36 keg/ml) showed good results after interferon treatment and two of them (13%) with genotypes 1b and 3 according to Simmond's classification showed a maintained response. The four HGV children also showed the same good results and the RNA was negative without sero-conversion to anti-E2 after 12 months of interferon treatment. In the post-interferon treatment period, the HGV RNA appeared again in the serum in 3 of the 4 children. In the child with a maintained response, serum conversion to anti-E2 was not detected. CONCLUSIONS: 1) The current results, with only 13% of the patients reaching a sustained response, question the systematic treatment of all children affected with hepatitis C virus. Since the cost-benefit ratio is not yielding the expected results, such therapy may be reserved for patients with genotype other than 1b and a low level of viral genome. 2) HGV is sensitive to treatment with interferon, although the infection frequently appears again once the treatment is over.

[Should the medico-surgical strategy for biliary atresia be changed in view of liver transplantation as a reality?]. / Debe cambiar la estrategia medico-quirúrgica de la atresia biliar ante la realidad del trasplante hepático?

Biliary atresia (BA) is the main source of candidates for paediatric liver transplantation (PLTx) with 64 per 100 of survival. The follow-up of 35 immediate candidates of BA, 19 of them transplanted, induced to the authors to change some details on the BA treatment. This disorder does not finish already with portoenterostomy. Eventually mortality causes are infection and chronic rejection. The functional loss of jejunal segment in the Roux en Y may explain the poor cyclosporin absorption and therefore chronic rejection. By other hand, chronic malnutrition presented by these patients before PLTx may favour infection. Authors recommend more aggressive medical treatment before PLTx and technical improvement in the portoenterostomy with the aim of previous surgery does not difficult posterior PLTx.

[Neonatal cholestatic icterus simulating atresia of the bile ducts in a patient with alpha-1-antitrypsin deficiency]. / Ictericia colestásica neonatal simulando atresia de vías biliares en un paciente con déficit de alfa-1-antitripsina.

A 40 days old infant with cholestasis is described. The liver was enlarged at 3 cm below the costal margin. No bile ducts were seen at the liver scan (IDA Tc 99) neither bile was collected after cholecystokinine IV administration. Fibrosi, bile ducts proliferation, and cholestasis without intracellular PAS positive material were seen at liver biopsy. Serum alpha-1-antitrypsin level was 42 mg/100 ml. Follow-up was satisfactory after phenobarbital and cholestiramine treatment. Cholestasis decreased and two weeks later bile excretion was obtained after cholecystokinine administration. This stress the importance of alpha-1-antitrypsin determination in cholestasis in infancy.