Efficacy of pegylated interferon-α2a monotherapy in Japanese children with chronic hepatitis C.

AIM: There is little information available on the efficacy of pegylated interferon (PEG IFN) therapy for children with chronic hepatitis C. The aim of this study was to evaluate the efficacy and tolerability of PEG IFN-α2a monotherapy for children infected by chronic hepatitis C virus (HCV). METHODS: From 2004-2006, we conducted a prospective, open-label, multicenter study of 22 patients aged 4-18 years, including eight with genotype 1 and 14 with genotype 2. None had previously received IFN. The patients were treated with s.c. PEG IFN-α2a at a dose of 3 µg/kg once a week for 48 weeks. Rapid virological response (RVR) was defined as: undetectable serum HCV RNA at week 4; early viral response (EVR) as a 2 or more log reduction or undetectable serum HCV RNA at week 12; and sustained viral response (SVR) as undetectable serum HCV RNA at 24 weeks after the cessation of treatment. RESULTS: SVR was achieved in 10 (45%) of the 22 patients (three with genotype 1, seven with genotype 2). Retrospectively, the patients with SVR included five with RVR (one with genotype 1, four with genotype 2) and five with EVR (two with genotype 1, three with genotype 2). PEG IFN-α2a monotherapy was well tolerated, except in one patient in whom alanine aminotransferase activity flared (>500 IU/L) during treatment. CONCLUSION: The efficacy of PEG IFN-α2a monotherapy in children is similar to that for adults, while tolerability seems to be better in children than in adults.

Serum magnesium concentration in children with functional constipation treated with magnesium oxide.

AIM: To determine whether hypermagnesemia recently reported in adult patients possibly develops in children with functional constipation taking daily magnesium oxide. METHODS: We enrolled 120 patients (57 male and 63 female) aged 1-14 years old (median: 4.7 years) with functional constipation from 13 hospitals and two private clinics. All patients fulfilled the Rome III criteria for functional constipation and were treated with daily oral magnesium oxide for at least 1 mo. The median treatment dose was 600 (500-800) mg/d. Patients were assessed by an interview and laboratory examination to determine possible hypermagnesemia. Serum magnesium concentration was also measured in sex- and age-matched control subjects (n = 38). RESULTS: In the constipation group, serum magnesium concentration [2.4 (2.3-2.5) mg/dL, median and interquartile range] was significantly greater than that of the control group [2.2 (2.0-2.2) mg/dL] (P < 0.001). The highest value was 3.2 mg/dL. Renal magnesium clearance was significantly increased in the constipation group. Serum magnesium concentration in the constipation group decreased significantly with age (P < 0.01). There was no significant correlation between the serum level of magnesium and the duration of treatment with magnesium oxide or the daily dose. None of the patients had side effects associated with hypermagnesemia. CONCLUSION: Serum magnesium concentration increased significantly, but not critically, after daily treatment with magnesium oxide in constipated children with normal renal function.

Inflammatory bowel disease in children: epidemiological analysis of the nationwide IBD registry in Japan.

OBJECTIVE: We analyzed the database of the Japanese nationwide inflammatory bowel disease (IBD) registry, which was started in 1975, to characterize basic epidemiological and clinical features of childhood IBD, comparing them to those in adults. STUDY DESIGN: We analyzed the age of disease onset, disease severity and anatomical distribution in patients that were newly registered between 2003 and 2006 (n = 2,940 for CD and 14,857 for UC). We also analyzed the current age, gender and family history of IBD of all patients filed in 2005, which included patients who were newly registered in 2005 and those who had been registered before 2005 and for whom an annual report had been received in 2005 (total number of subjects: 10,934 for CD and 37,846 for UC). RESULTS: At the time of registration, 10.6% of CD and 5.9% of UC patients were ≤ 16 years old. In CD, the male to female ratio was 2.6 in adult- and 1.7 in childhood-onset patients (P < 0.001). In UC, the male to female ratio was close to 1 in both age groups. In comparison with adults, pediatric patients more commonly had a positive family history for CD and UC (P < 0.001), tended to have more severe disease at the time of registry (P < 0.001 for CD, P < 0.05 for UC) and more often had extensive colitis in UC (P < 0.001). CONCLUSION: The nationwide registry in Japan showed IBD in children has clinical features that are distinct from those in adults.

Effects of pectin liquid on gastroesophageal reflux disease in children with cerebral palsy.

BACKGROUND: The use of thickeners is a standard therapy for decreasing episodes of regurgitation or vomiting in infants. However, it remains to be investigated whether thickener is effective for vomiting and/or chronic respiratory symptoms in children with cerebral palsy. METHODS: We enrolled 18 neurologically impaired children caused by cerebral palsy, with gastroesophageal reflux disease. In the first part of this study (pH monitoring), subjects were randomly allocated to two groups: fed with a high-pectin diet [enteral formula: pectin liquid = 2:1 (v/v)], or a low-pectin diet [enteral formula: pectin liquid = 3:1 (v/v)]. Two-channel esophageal pH monitoring was performed over 48 h. In the second part (clinical trial), subjects were fed a high- or low-pectin diet and non-pectin diet for 4 weeks in a crossover manner. Nurses recorded the feeding volume, number of episodes of vomiting, volume of gastric residue, episodes of cough and wheeze, frequency of using oxygen for dyspnea, and the day when the child could return to school. Cough and wheeze were recorded as a cough-score. RESULTS: The median value for the % time pH < 4 at the lower and upper esophagus was significantly decreased with a high-pectin diet [9.2% (6.2-22.6) vs. 5.0% (3.1-13.1); P < 0.01, 3.8% (2.9-11.2) vs. 1.6% (0.9-8.9); P < 0.01 (interquartile range), non-pectin and high-pectin, respectively]. The number of reflux episodes per day and duration of longest reflux were decreased significantly with a high-pectin, but not with a low-pectin diet. The median number of episodes of vomiting decreased significantly with a high-pectin diet [2.5/week (1.0-5.0) vs. 1.0 (1.0-1.5), P < 0.05]. The median cough-score was significantly decreased by both concentrations of pectin [8.5/week (1.0-11.5) vs. 2.0/week (0.0-3.0), fed with a high-pectin diet; 7.0/week (1.0-14.5) vs. 1.0/w (0.0-5.0), fed with a low-pectin diet, P < 0.05]. CONCLUSION: Pectin liquid partially decreased gastroesophageal reflux as measured by eshophageal pH monitoring, and might improve vomiting and respiratory symptoms in children with cerebral palsy. TRIAL REGISTRATION: ISRCTN19787793.

Pemphigus vulgaris as a possible cause of protein-losing gastroenteropathy: a case report.

We present a case of pemphigus vulgaris (PV) accompanied with protein-losing gastroenteropathy (PLE). A 9-year-old girl developed multiple oral ulcerations and erosions. She was first treated with oral antibiotics and a topical steroid without improvement. Laboratory data showed eosinophilia (absolute eosinophil count 1.08 x 10(9)/L) and hypoproteinemia (total serum protein 3.9 g/dL, albumin 2.2 g/dL). A biopsy specimen from the ileum showed intense eosinophil infiltration and albumin scintigraphy demonstrated protein exduation from the same site. Endoscopic examination of the oesophagus showed multiple ulcerations and erosions, and biopsy specimen showed eosinophilic spongiosis and immunohistologic staining demonstrated deposits of IgG and C3 in the intercellular space. Antidesmoglein-3 antibody elevated, she was diagnosed as PV complicated with PLE. Immunofluorescence study of a biopsy specimen from the terminal ileum showed no significant immunoglobulin or complement deposition, and autoantibody against intestinal mucosa was unclear in this case. Gastrointestinal evaluations should be considered in patients with hypoproteinemia associated with PV.

Effect of formula thickened with locust bean gum on gastric emptying in infants.

AIM: We investigated the effects of milk-based formulas thickened with two different concentrations of locust bean gum on gastric emptying in infants with recurrent regurgitation episodes. METHODS: Thirty-nine infants with three or more episodes of regurgitation per day but no complications who were fed mainly with infant formula were studied. We first compared gastric emptying in infants fed with formulas thickened with two different concentrations of locust bean gum (HL-350, 0.35 g/100 mL; HL-450, 0.45 g/100 mL) or a regular formula (HL-00). To evaluate gastric emptying, we measured antral cross-sectional areas ultrasonographically at various time points after feeding. Next, to investigate the clinical effect of thickened formulas on regurgitation episodes, 27 infants with episodes were assigned randomly to receive HL-350 and HL-00 or HL-450 and HL-00 for 1 week each. RESULTS: Antral cross-sectional areas at 60, 90, 120 and 150 min with HL-450, and at 60 min with HL-350, were greater than with HL-00. The median gastric emptying rate at 120 min with HL-450 (52.8%) was lower than with HL-00 (97.9%; P = 0.0019), while HL-350 (80.3%) and HL-00 did not differ significantly. The mean number of regurgitation episodes was significantly smaller when infants were fed with either HL-350 or HL-450 than with HL-00. CONCLUSIONS: HL-450, a thickened formula with typical commercially available concentrations of locust bean gum, slowed gastric emptying in infants with gastroesophageal reflux.

Possible involvement of adrenomedullin in lipopolysaccharide-induced small-intestinal motility changes in conscious rats.

BACKGROUND: Adrenomedullin is a vasodilator peptide that displays a variety of effects, such as hypotension and vasodilatation. The aim of this study was to test the effect of intravenous adrenomedullin on the motility pattern of the small intestine, and the functional involvement of adrenomedullin in endotoxin-induced small-intestinal motility disturbance. METHODS: Jejunal motility was recorded in fasted conscious rats, using miniature strain-gauge force transducers sutured to the serosal surface of the small-intestinal wall. RESULTS: Intravenous administration of adrenomedullin at doses of 3, 6, and 10 microg/kg per min over 30 min disrupted phase 3 of the migrating motor complex, with the disruption lasting for 61.9 +/- 5.1, 52.2 +/- 10.6, and 74.1 +/- 25.2 min, respectively. The interval from drug administration to the onset of disruption decreased as the dose of adrenomedullin increased to 41.5 +/- 11.0, 11.6 +/- 3.4, and 0 min, respectively (P < 0.05). An increase in the motility index was also dose-dependent (P < 0.05) at these doses of adrenomedullin. Lipopolysaccharide (50 microg/kg) induced disruption of phase 3, which lasted for 138.7 +/- 5.4 min. Previous administration of the putative adrenomedullin-receptor antagonist, AM (22-52), at a 50 microg/kg dose, attenuated the disruption induced by lipopolysaccharide to 74.4 +/- 3.5 min (P < 0.01). CONCLUSIONS: Our findings (1) suggest that intravenous adrenomedullin causes small-intestinal motility disturbances, and (2) support the hypothesis that adrenomedullin overproduction plays an important role in lipopolysaccharide-induced disruption of the motility pattern in the small intestine in rats.

Effect of locust bean gum in anti-regurgitant milk on the regurgitation in uncomplicated gastroesophageal reflux.

OBJECTIVES: To evaluate the efficacy of anti-regurgitant milk (AR milk) with reduced concentration of locust bean gum (LBG) compared with the usual commercially available concentration of this thickener. METHODS: Thirty infants with daily regurgitation but no other medical problems were randomly assigned to one of two groups. Infants in group A (n = 16) were fed either HL-450, an AR milk thickened with a commonly used concentration of LBG (0.45 g/100 mL) or control milk (HL-00; no LBG) in a crossover manner for periods of 1 week. The order of milk was randomly chosen for each subject. Infants in group B (n = 14) were fed HL-350, an AR milk with a reduced LBG concentration (0.35 g/100 mL), or HL-00 in the same crossover fashion. The number of episodes of regurgitation, feeding time, and body weight gain were recorded. Three infants in group B did not complete the protocol and were excluded. RESULTS: Both AR formulas decreased the number of regurgitation episodes by approximately 50% compared with control. Five mothers who gave their infants HL-450 and no mothers who fed their children HL-350 reported that the infants had difficulty sucking the formula through the nipple. Thirteen (81.3%) mothers who used HL-450 and 9 (81.8%) mothers who used HL-350 preferred the AR milk to the control milk. CONCLUSIONS: An AR milk with reduced LBG was as effective in reducing regurgitation as one with the usually available concentration of LBG.

Pharmacobezoar complicating treatment with sodium alginate.

We encountered a gastric bezoar that had developed in a 9-year-old girl treated with sodium alginate (Alloid G) for acute gastritis associated with systemic lupus erythematosus. A hard mass palpated in the left upper abdomen proved, upon gastric endoscopy, to be an intragastric foreign body. Sodium alginate was detected in an analysis of a sample from this bezoar. In an in vitro simulation, sodium alginate solidified when mixed with the patient's other medicines. The bezoar caused no complications, and disappeared spontaneously after discontinuation of the medications. This case indicates that this sodium alginate preparation, Alloid G, can be a cause of pharmacobezoar.

Determinants of prognosis of acute transverse myelitis in children.

BACKGROUND: Acute transverse myelitis (ATM) is a severe disorder; recovery requires several months and often leaves neurologic residua. To determine what features of patients with acute transverse myelitis significantly influence prognosis, the authors reviewed reports of ATM in Japanese children published in the last 15 years (from 1987 to 2001). METHODS: The authors studied reports of 50 Japanese patients (17 boys, 26 girls, 7 children of unspecified sex; mean age +/- SD, 8.0 +/- 3.8 years). Acute-phase and demographic features including age, increased deep tendon reflexes, Babinski reflex, sex, preceding infection, decreased deep tendon reflexes, time course of peak neurologic impairment, treatment with prednisolone and/or high-dose methylprednisolone, and the day of illness when treatment was started were used as independent variables in a regression analysis. The dependent variable was long-term persistence of neurologic deficits. RESULTS: Younger patients and those without increased deep tendon reflexes or a Babinski reflex were more likely to have residual neurologic deficits such as paraplegia or tetraplegia, sensory loss and sphincter disturbance. No relationship was seen between prognosis and sex, preceding infections, decreased deep tendon reflexes, time course of peak neurologic impairment, treatment with prednisolone or high-dose methylprednisolone, or timing of treatment initiation. CONCLUSIONS: Age at onset and neurologic features were important for outcome prediction in ATM. Steroid therapy did not associate with better outcome.

Prevalence of gastro-esophageal reflux-related symptoms in Japanese infants.

BACKGROUND: To obtain precise information on the natural course of gastro-esophageal reflux (GER)-related symptoms in Japanese children, we surveyed the prevalence of regurgitation or vomiting and other GER-related symptoms and complications in infants visiting for healthy baby check-ups. METHODS: We interviewed the mothers of 921 infants who had visited for baby check-ups at 1, 4, 7 and 12 months after birth, about the number of regurgitation or vomiting episodes per day, other GER-related symptoms, milk volume, feeding interval, and the body position after feeding. RESULTS: Of 1-month-old infants, 47.1% had one or more regurgitation or vomiting episode per day. This proportion decreased to 28.8% at 4 months old and 6.4% at 7 months old. The proportion of infants with three or more episodes of these symptoms per day showed a similar pattern. There was no significant difference in the prevalence of regurgitation or vomiting between breast-fed infants and formula-fed or mixed-feeding infants either at 1 or 4 months of age. There was no significant difference in the bodyweight gain of 3-month-old infants among those with various degrees of regurgitation. There was no significant difference in the frequency of regurgitation or vomiting episodes between infants placed in a vertical position and those placed in a horizontal position after feeding. No infant had a history of chronic coughing, wheezing, bleeding or other serious conditions. CONCLUSIONS: Regurgitation is a common symptom in Japanese infants and decreases spontaneously with age. The natural history of GER must be taken into consideration when deciding the treatment.