A randomised, double-blind study of polyethylene glycol 4000 and lactulose in the treatment of constipation in children.

BACKGROUND: Chronic constipation is frequent in children. The objective of this study is to compare the efficacy and safety of PEG 4000 and lactulose for the treatment of chronic constipation in young children. METHODS: This randomised, double-blind study enrolled 88 young children aged 12 to 36 months, who were randomly assigned to receive lactulose (3.3 g per day) or PEG 4000 (8 g per day) for four weeks. The primary efficacy variable was stool frequency during the fourth week of treatment. Secondary outcomes were the number and frequency of subjective symptoms associated with defecation at each visit. RESULTS: Stool frequency was comparable in the two groups at baseline (lactulose: 0.7 ± 0.5; PEG 4000: 0.5 ± 0.55). Mean stool frequency increased from 0.70 ± 0.50 stools/day at baseline to 0.80 ± 0.41 at Week 4 in the lactulose group and from 0.50 ± 0.55 to 1.10 ± 0.55 stools/day in the PEG 4000 group. A significant difference was observed in the adjusted mean change from baseline, which was 0.15 stools/day in the lactulose group and 0.51 stools/day in the PEG 4000 group, with a least-squares mean difference of 0.36 stools/day [95% CI: 0.16 to 0.56]. With respect to secondary outcome variables, stool consistency and ease of stool passage improved more in the PEG 4000 group (p = 0.001). The incidence of adverse events was similar in both groups, the majority of which were mild. CONCLUSIONS: PEG 4000 has superior efficacy to lactulose for the treatment of chronic constipation in young children and is well tolerated. TRIAL REGISTRATION: US National Institute of Health Clinical Trials database; study NCT00255372 first registered 17th November 2005.

Neonatal intrahepatic cholestasis caused by citrin deficiency: prevalence and SLC25A13 mutations among Thai infants.

BACKGROUND: The most common causes of cholestatic jaundice are biliary atresia and idiopathic neonatal hepatitis (INH). Specific disorders underlying INH, such as various infectious and metabolic causes, including neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) especially, in East Asian populations are increasingly being identified. Since most NICCD infants recovered from liver disease by 1 year of age, they often are misdiagnosed with INH, leading to difficulty in determining the true prevalence of NICCD. Mutation(s) of human SLC25A13 gene encoding a mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), can lead to AGC2 deficiency, resulting in NICCD and an adult-onset fatal disease namely citrullinemia type II (CTLN2). To study the prevalence of NICCD and SLC25A13 mutations in Thai infants, and to compare manifestations of NICCD and non-NICCD, infants with idiopathic cholestatic jaundice or INH were enrolled. Clinical and biochemical data were reviewed. Urine organic acid and plasma amino acids profiles were analyzed. PCR-sequencing of all 18 exons of SLC25A13 and gap PCR for the mutations IVS16ins3kb and Ex16+74_IVS17-32del516 were performed. mRNA were analyzed in selected cases with possible splicing error. RESULTS: Five out of 39 (12.8%) unrelated infants enrolled in the study were found to have NICCD, of which three had homozygous 851del4 (GTATdel) and two compound heterozygous 851del4/IVS16ins3kb and 851del4/1638ins23, respectively. Two missense mutations (p.M1? and p.R605Q) of unknown functional significance were identified. At the initial presentation, NICCD patients had higher levels of alkaline phosphatase (ALP) and alpha-fetoprotein (AFP) and lower level of alanine aminotransferase (ALT) than those in non-NICCD patients (p< 0.05). NICCD patients showed higher citrulline level and threonine/serine ratio than non-NICCD infants (p< 0.05). Fatty liver was found in 2 NICCD patients. Jaundice resolved in all NICCD and in 87.5% of non-NICCD infants at the median age of 9.5 and 4.0 months, respectively. CONCLUSION: NICCD should be considered in infants with idiopathic cholestasis. The preliminary estimated prevalence of NICCD was calculated to be 1/48,228 with carrier rate of 1/110 among Thai infants. However, this number may be underestimated and required further analysis with mutation screening in larger control population to establish the true prevalence of NICCD and AGC2 deficiency.

Acute pancreatitis in children with acute lymphoblastic leukemia after chemotherapy.

BACKGROUND: Acute pancreatitis (AP) is a complication in children with acute lymphoblastic leukemia (ALL) receiving chemotherapy and has often been reported associated with L-asparaginase (L-asp) therapy. OBJECTIVES: To determine the incidence, risk factors, clinical data, outcome, and mortality of AP in children with ALL. METHODS: Retrospective cohort study was conducted by reviewing the data of total 192 pediatric ALL patients from Pediatric Oncology Registry at Ramathibodi Hospital from 2000 to 2006 to assess incidence, clinical data, outcome, and mortality of AP. Then, a nested case-control study was conducted to identify potential risk factors for AP by recruiting all patients with AP as cases (n=16), and randomly selected patients without AP to serve as controls up to approximately four controls per case with the total of 68 controls. RESULTS: The total incidence of AP in children with ALL and L-asp-associated AP was 8.3% and 7.3%, respectively. In patients with L-asp-associated AP, pancreatitis developed after the median 5.5 doses (range: 1 to 20 doses) of L-asp therapy and the median interval from the last dose of L-asp to the onset of AP was 4 days (range: 1 to 13 days). The mortality rate of AP group was significantly higher than the patients without AP (43.8% vs. 19.3%, P=0.02). Mortality was associated with concurrent systemic infection and complications of underlying diseases. Multivariate analysis identified using a high-risk chemotherapy regimen was the only risk factor for AP. CONCLUSIONS: Using a high-risk chemotherapy regimen was a risk factor for pancreatitis in patients with ALL. ALL children with AP had higher mortality rate than those without pancreatitis.

Genetic polymorphisms in Thai neonates with hyperbilirubinemia.

AIM: Polymorphisms of the UGT1A1 gene, SLCO1B1 gene and GST gene have been associated with significant hyperbilirubinemia. We would like to determine whether the variation of UGT1A1 gene, SLCO1B1 gene and GST gene may play a significant role in neonatal hyperbilirubinemia in Thai infants. METHODS: Ninety-one study subjects (hyperbilirubinemic group) and 86 control subjects were studied. RESULTS: The cause of neonatal hyperbilirubinemia could not be identified in 64 infants (70.3%), ABO blood group incompatibility in 14.3% and Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in 8.8%. In the hyperbilirubinemic group, 23 of 91 (25.3%) infants demonstrated variant of UGT1A1 at nucleotides (nt) 211 as compared to 6 of 86 (7%) in the control group (p = 0.001). There were no significant differences between groups in the variants UGT1A1 at nt 686, SLCO1B1 gene at nt 388, 463 and the GST gene. Male infants with G-6-PD deficiency were associated with hyperbilirubinemia (21.2% vs. 4.8% in the control group) with an odds ratio (OR) of 5.37 (p = 0.02). The relationship between G-6-PD and variant in UGT1A1 gene at nt 211 could not be determined. CONCLUSION: Thai infants with variant in the UGT1A1 at nt 211 or with G-6-PD deficiency are at higher risk for developing neonatal hyperbilirubinemia.

Inflammatory bowel disease in Thai children: presentations and outcomes of treatment.

Inflammatory bowel disease (IBD) is characterized by idiopathic chronic intestinal inflammation, due to abnormalities in gastrointestinal immunoregulation. Pediatric IBD has been rarely reported in Thailand. We describe eight children, five girls and three boys, who were diagnosed with IBD at Ramathibodi Hospital during 1999-2005 and had a follow-up of more than one year. Four cases had Crohn's disease (CD) and four cases had ulcerative colitis (UC). The ages at diagnosis ranged from 3.5 to 15.5 years. Diagnosis of IBD was delayed for more than 12 months in five patients. Five out of eight patients had early onset of disease, before 6 years of age. The manifestations included chronic diarrhea, abdominal pain, rectal bleeding and perianal lesions. The common extraintestinal manifestations were oral ulcer, anemia, weight loss and failure to thrive. Most patients had moderate to severe diseases and ileocolic fistula developed in one patient with CD. The disease was controlled with 5-aminosalicylic acid and corticosteroid in most patients. Four patients required additional therapy with azathioprine. Infliximab was used in two patients who were chronically steroid-dependent CD, one also had persistent ileocolic fistula and both patients responded well. During the follow-up period ranging from 1.1 to 5.8 years, three patients remained growth retardation; all had early onset of disease before 6 years of age, long duration of symptoms of more than 3 years before diagnosis and had multiple relapses. It is concluded that there is an increasing number of IBD in Thai children during the recent years. Most patients had moderate to severe diseases. Early onset of disease, delay in diagnosis and treatment are responsible for more complications, particularly persistent growth impairment. Early recognition of IBD and treatment are essential for a satisfactory long-term outcome.

Effects of sodium butyrate and acidic fibroblast growth factor on TDC32300 cultured cells.

BACKGROUND: Many studies have demonstrated that transition duct cells (TDC) are facultative liver stem cells. Our laboratory established TDC32300 cell lines with hepatic progenitor markers. The authors proposed that cell culture using sodium butyrate (NaBut) and acidic fibroblast growth factors (aFGF) may support the differentiation of TDC32300 cells along the hepatic lineage. METHODS: TDC32300 cells were cultured in four different conditions 1) STON media alone; 2) STON with NaBut in 3 different concentrations, 1 mM, 3.75 mM and 5 mM; 3) STON with aFGF; and 4) STON with aFGF and dexamethasone. After day 5, the cultured cells were fixed and stained with monoclonal antibodies to rat liver antigens and anti-proliferating nuclear antigen (PCNA). RESULTS: Proliferation of TDC32300 cells cultured in the high concentration of NaBut (3.75 and 5 mM) was inhibited. This phenomenon was confirmed by the reduction in cell number and decrease in PCNA expression. Irrespective of the concentration, NaBut did not alter the phenotype of the TDC32300 cultured cells. aFGF with or without dexamethasone also did not alter the phenotypic characteristic of TDC32300 cells. CONCLUSION: TDC32300 cells may not be the hepatic progenitors or that their differentiation may require other culture conditions.

Modified percutaneous endoscopic gastrostomy tubes: experience in Thai children.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a well-established alternative to open gastrostomy for providing long-term enteral nutrition. Although the commercial PEG tube is available and suitable for the procedure, its cost is relatively high for low socioeconomic people. Therefore, modified PEG tubes have been used in our hospital. OBJECTIVES: To evaluate the outcome and complications of PEG performed in children at Ramathibodi Hospital and compare the results between the commercial PEG and modified PEG tubes. METHOD: All children who had PEG performed at Ramathibodi Hospital, from January 1999 to May 2002, were included in the study. The demographic data, indications for PEG, types of PEG tube, outcomes and complications were retrospectively reviewed. The modified PEG tube was made by connecting a Malecot four-wing catheter to the previously used, re-sterilized distal part of a commercial PEG tube. RESULTS: PEG was performed on 34 children, aged 4 months to 13 years, and successfully placed in 30 children (88.2%). The commercial and modified PEG tubes were used in 20 cases and 10 cases, respectively. Early complications occurring in the first 7 days post-procedure were found in 9 cases (30%) as follow: peritonitis (1 case), peristomal wound infection (7 cases), and subcutaneous emphysema (1 case). Late complications occurring at more than 7 days post-procedure were found in 15 cases (50%) and all were minor problems. There was no difference in complication rates between the 2 types of PEG tubes. CONCLUSION: PEG is safe even in small infants. Minor complications are common but can be simply managed. The modified PEG tube is an alternative for a commercial PEG tube in an unaffordable situation.

Novel ABCB11 mutations in a Thai infant with progressive familial intrahepatic cholestasis.

Progressive familial intrahepatic cholestasis (PFIC) type 2 is caused by mutations in ABCB11, which encodes bile salt export pump (BSEP). We report a Thai female infant who presented with progressive cholestatic jaundice since 1 mo of age, with normal serum gamma-glutamyltransferase. Immunohistochemical staining of the liver did not demonstrate BSEP along the canaliculi, while multidrug resistance protein 3 was expressed adequately. Novel mutations in ABCB11, a four-nucleotide deletion in exon 3, c.90_93delGAAA, and a single-nucleotide insertion in exon 5, c.249_250insT, were identified, with confirmation in her parents. These mutations were predicted to lead to synthesis of truncated forms of BSEP. Immunostaining and mutation analysis thus established the diagnosis of PFIC type 2.

A rapid serologic test and immunoblotting for the detection of Helicobacter pylori infection in children.

The gold standard for the diagnosis of Helicobacter pylori infection requires an endoscopic biopsy of gastric mucosa for histological examination, urease test and culture. Noninvasive serological tests are useful as a screening test for H. pylori infection. The aim of this study was to evaluate the performance of a rapid office-based serologic test, using immunochromatography ICM, and the immunoblotting for the diagnosis of H. pylori infection in Thai children. Eighty-two symptomatic children, 30 boys and 52 girls (mean age 9.2+/-3.8 years; range, 1.2-16.0 years) who had no previous treatment for H. pylori underwent upper endoscopy. Biopsies were obtained from the gastric body and antrum for histopathology and rapid urease test. Serum samples collected from all patients were tested for H. pylori IgG antibodies using ICM (Assure H. pylori Rapid Test, Genelabs Diagnostics, Singapore). Immunoblotting (HelicoBlot 2.1, Genelabs Diagnostics, Singapore) was tested in sera of 75 patients to detect antibodies to specific antigens of H. pylori. Positive H. pylori status was defined as positive for both histology and rapid urease test. Of 82 patients, 25 (30.5%) were H. pylori positive, 56 (68.3%) were H. pylori negative and one was equivocal. ICM assay yielded a positive result in 24 of the 25 H. pylori-positive patients (96.0%) and 3 of the 56 H. pylori-negative patients (5.4%). The immunoblotting yielded a positive result in all of 22 H. pylori-positive patients (100%) and in 2 of the 52 H. pylori-negative patients (3.8%). Obtained ICM's sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 96.0, 94.6, 88.9, 98.1 and 95.1%, with immunoblotting 100.0, 96.2, 91.6, 100.0, and 97.3%, respectively. The immunochromatographic and immunoblot tests are non-invasive, reliable and useful for the diagnosis of H. pylori infection in Thai children.

Inflammatory bowel disease in Thai children: presentations and outcomes of treatment.

Inflammatory bowel disease (IBD) is characterized by idiopathic chronic intestinal inflammation, due to abnormalities in gastrointestinal immunoregulation. Pediatric IBD has been rarely reported in Thailand. We describe eight children, five girls and three boys, who were diagnosed with IBD at Ramathibodi Hospital during 1999-2005 and had a follow-up of more than one year. Four cases had Crohn's disease (CD) and four cases had ulcerative colitis (UC). The ages at diagnosis ranged from 3.5 to 15.5 years. Diagnosis of IBD was delayed for more than 12 months in five patients. Five out of eight patients had early onset of disease, before 6 years of age. The manifestations included chronic diarrhea, abdominal pain, rectal bleeding and perianal lesions. The common extraintestinal manifestations were oral ulcer, anemia, weight loss and failure to thrive. Most patients had moderate to severe diseases and ileocolic fistula developed in one patient with CD. The disease was controlled with 5-aminosalicylic acid and corticosteroid in most patients. Four patients required additional therapy with azathioprine. Infliximab was used in two patients who were chronically steroid-dependent CD, one also had persistent ileocolic fistula and both patients responded well. During the follow-up period ranging from 1.1 to 5.8 years, three patients remained growth retardation; all had early onset of disease before 6 years of age, long duration of symptoms of more than 3 years before diagnosis and had multiple relapses. It is concluded that there is an increasing number of IBD in Thai children during the recent years. Most patients had moderate to severe diseases. Early onset of disease, delay in diagnosis and treatment are responsible for more complications, particularly persistent growth impairment. Early recognition of IBD and treatment are essential for a satisfactory long-term outcome.

Effects of sodium butyrate and acidic fibroblast growth factor on TDC32300 cultured cells.

BACKGROUND: Many studies have demonstrated that transition duct cells (TDC) are facultative liver stem cells. Our laboratory established TDC32300 cell lines with hepatic progenitor markers. The authors proposed that cell culture using sodium butyrate (NaBut) and acidic fibroblast growth factors (aFGF) may support the differentiation of TDC32300 cells along the hepatic lineage. METHODS: TDC32300 cells were cultured in four different conditions 1) STON media alone; 2) STON with NaBut in 3 different concentrations, 1 mM, 3.75 mM and 5 mM; 3) STON with aFGF; and 4) STON with aFGF and dexamethasone. After day 5, the cultured cells were fixed and stained with monoclonal antibodies to rat liver antigens and anti-proliferating nuclear antigen (PCNA). RESULTS: Proliferation of TDC32300 cells cultured in the high concentration of NaBut (3.75 and 5 mM) was inhibited. This phenomenon was confirmed by the reduction in cell number and decrease in PCNA expression. Irrespective of the concentration, NaBut did not alter the phenotype of the TDC32300 cultured cells. aFGF with or without dexamethasone also did not alter the phenotypic characteristic of TDC32300 cells. CONCLUSION: TDC32300 cells may not be the hepatic progenitors or that their differentiation may require other culture conditions.

Modified percutaneous endoscopic gastrostomy tubes: experience in Thai children.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a well-established alternative to open gastrostomy for providing long-term enteral nutrition. Although the commercial PEG tube is available and suitable for the procedure, its cost is relatively high for low socioeconomic people. Therefore, modified PEG tubes have been used in our hospital. OBJECTIVES: To evaluate the outcome and complications of PEG performed in children at Ramathibodi Hospital and compare the results between the commercial PEG and modified PEG tubes. METHOD: All children who had PEG performed at Ramathibodi Hospital, from January 1999 to May 2002, were included in the study. The demographic data, indications for PEG, types of PEG tube, outcomes and complications were retrospectively reviewed. The modified PEG tube was made by connecting a Malecot four-wing catheter to the previously used, re-sterilized distal part of a commercial PEG tube. RESULTS: PEG was performed on 34 children, aged 4 months to 13 years, and successfully placed in 30 children (88.2%). The commercial and modified PEG tubes were used in 20 cases and 10 cases, respectively. Early complications occurring in the first 7 days post-procedure were found in 9 cases (30%) as follow: peritonitis (1 case), peristomal wound infection (7 cases), and subcutaneous emphysema (1 case). Late complications occurring at more than 7 days post-procedure were found in 15 cases (50%) and all were minor problems. There was no difference in complication rates between the 2 types of PEG tubes. CONCLUSION: PEG is safe even in small infants. Minor complications are common but can be simply managed. The modified PEG tube is an alternative for a commercial PEG tube in an unaffordable situation.