Atsushi Yoden

Granulocyte adsorptive apheresis for pediatric patients with ulcerative colitis.

Granulocytapheresis (GCAP) has produced efficacy in adult patients with ulcerative colitis (UC) by adsorbing activated granulocytes and monocytes/macrophages. We retrospectively investigated efficacy and safety of GCAP in pediatric patients with active UC. Twelve steroid-refractory children (12.2±3.1 years old) were treated with GCAP, one session/week for 5–10 consecutive weeks. In 8 patients, clinical symptoms improved after two GCAP sessions. Normal body temperature, stool frequency, and disappearance of blood in stool were seen after 24.3±11.5 days. The endoscopic grade improved from 2.6±0.3 to 0.4±0.2. One patient who initially responded, developed bloody diarrhea later and 2 cases remained unchanged. The dose of steroid was tapered during GCAP therapy by 50%. No serious adverse effects were noted. Four of 8 cases relapsed 3.5 ± 2.2 months after the last GCAP while on maintenance therapy, the other 4 were in remission up to 22.8±18.1 months. In conclusion, GCAP appears to be effective and well tolerated in children with steroid-refractory UC.

Management and ultrasonographic appearance of infantile hypertrophic pyloric stenosis with intravenous atropine sulfate.

Some infants with hypertrophic pyloric stenosis (HPS) have responded to oral atropine treatment. To achieve sufficient effect of atropine, it must be administered intravenously (i.v.). Therefore, with ultrasonography, we studied the changes in the pyloric muscle in HPS during and after intravenous administration of atropine. Twenty-three infants were studied. Atropine sulfate was initially administered at a dose of 0.04 mg/kg day i.v., and the dose was increased by 0.01 mg/kg/day until vomiting ceased. When vomiting ceased after administration of intravenous atropine sulfate, the infants received oral atropine sulfate at twice the effective intravenous dose; this was continued for 2 weeks. Ultrasonography was repeated until pyloric muscles normalized. Twenty-two infants were free from vomiting after 1-8 days of intravenous atropine sulfate (dosages of 0.04-0.11 mg/kg/day). In 21 infants, weight gain continued after atropine treatment even though no change in thickness of the pyloric muscles was demonstrated ultrasonographically. Only 2 infants required pyloromyotomy because of prolonged treatment or a mistake in underdosing of oral atropine. All of the 21 infants who recovered after intravenous atropine without surgery had normalization of pyloric muscle caliber, as shown by ultrasonography 4-12 months after treatment. Atropine is an effective medicine for HPS. Regression of pyloric thickening after vomiting has been controlled implies that pyloric muscle hypertrophy could be worsened by the spasm that occurs in HPS.

Faecal chitinase 3-like-1: a novel biomarker of disease activity in paediatric inflammatory bowel disease

Aliment Pharmacol Ther 2011; 34: 941–948

Terminal Restriction Fragment Length Polymorphism Analysis of the Gut Microbiota Profiles of Pediatric Patients with Inflammatory Bowel Disease

Background/Aim: We analyzed the fecal microbiota profiles of pediatric patients with inflammatory bowel disease. Method: Terminal restriction fragment length polymorphism analysis was performed in 10 fecal samples from Crohn’s disease (CD), 14 samples from ulcerative colitis (UC) and 27 samples from healthy individuals. The bacterial diversity was evaluated by the Shannon diversity index. Result: In CD patients, a setting of similarity generated three major clusters. The majority of CD patients were classified into CD clusters I and II (9 out of 10), but the majority of healthy individuals (21 of 27) were classified into CD cluster III. In UC patients, a setting of similarity also generated three major UC clusters, but each cluster was not characteristic for UC patients or healthy individuals. The changes in simulated bacterial composition indicated that the class Clostridia, including the genus Faecalibacterium, was significantly decreased in CD patients as compared to UC patients and/or healthy individuals. The genus Bacteroides was also decreased as compared to healthy individuals. The bacterial diversity measured by the Shannon diversity index was significantly reduced in CD patients as compared to healthy individuals. Conclusion: The gut microbiota profile of pediatric CD patients was different from that of healthy children.

Efficacy and Safety of Azathioprine and 6-Mercaptopurine in Japanese Pediatric Patients with Ulcerative Colitis: A Survey of the Japanese Society for Pediatric Inflammatory Bowel Disease

Background and Aims: Azathioprine (AZA) and 6-mercaptopurine (6-MP) have recently been used in Japanese pediatric patients with ulcerative colitis. The aims of this study were to evaluate both the therapeutic efficacy and safety of AZA/6-MP in this group of patients. Methods: Fourteen members of the Japanese Society for Pediatric Inflammatory Bowel Disease reported 35 retrospective cases that received AZA/6-MP and were evaluated for adverse drug effects. In those who tolerated AZA/6-MP, disease activity and corticosteroid doses before and during the first 6 months of therapy were assessed. Results: AZA or 6-MP was safely used in 21 of 35 patients (60%) without adverse drug effects. The disease activity began to decrease from the first month of therapy and the maximum effect was achieved after 3 months. The mean daily prednisolone dose was decreased from 26.9 to 11.6 mg and dose reduction was achieved in 58% of patients after 6 months of therapy. Fourteen of the 35 patients (40%) experienced adverse drug effects, including leukopenia (n = 11), aplastic anemia (n = 1), pancreatitis (n = 1) and liver dysfunction (n = 1). Conclusions: The majority of Japanese children with ulcerative colitis tolerated AZA/6-MP and experienced favorable effects. However, 40% experienced adverse drug effects, mainly myelosuppression.

Characteristics of inflammatory bowel disease with an onset before eight years of age: A multicenter epidemiological survey in Japan

Pediatric inflammatory bowel disease (IBD) has not been rare in Japan since the 1990s. The present study attempted to define the epidemiological and clinical characteristics of early‐childhood IBD in Japan in comparison with results from Western countries.

Tacrolimus (FK506) suppresses TNF-α-induced CCL2 (MCP-1) and CXCL10 (IP-10) expression via the inhibition of p38 MAP kinase activation in human colonic myofibroblasts.

In order to investigate the molecular mechanisms underlying the immunosuppressive effects of tacrolimus (FK506) on intestinal inflammation, we examined whether FK506 effects cytokine/chemokine secretion in human colonic myofibroblasts. Human colonic myofibroblasts were isolated from normal human colonic tissue. The mRNA and protein expression for human CCL2 and CXCL10 were analyzed by real-time PCR and ELISA, respectively. p38 MAP kinase activation was evaluated by western blotting. Tacrolimus (1 µM) suppressed tumor necrosis factor (TNF)-α-induced CCL2 and CXCL10 mRNA expression, but did not modulate TNF-α-induced interleukin (IL)-6 or CXCL8 mRNA expression. Dose-dependent, inhibitory effects of tacrolimus on CCL2 and CXCL10 expression were observed at the mRNA and protein levels. Significant inhibitory effects of tacrolimus were observed at concentrations as low as 0.5 µM for CCL2 and 0.1 µM for CXCL10, respectively. TNF-α-induced CCL2 and CXCL10 expression depended on p38 MAP kinase activation, and tacrolimus strongly inhibited the TNF-α-induced phosphorylation of p38 MAP kinase. Tacrolimus did not affect interferon (IFN)-γ-induced signaling transducer and activator of transcription (STAT)-1 phosphorylation, nor did it modulate CXCL10 mRNA and protein expression. In conclusion, tacrolimus suppressed CCL2 and CXCL10 expression in human colonic myofibroblasts. These inhibitory effects of tacrolimus may play key roles in the therapeutic effects of colonic inflammation in inflammatory bowel disease (IBD) patients.

Fulminant hepatitis B and acute hepatitis B due to intrafamilial transmission of HBV after chemotherapy for non-Hodgkin’s lymphoma in an HBV carrier

Hepatitis B virus (HBV) reactivation after chemotherapy has been investigated, but little is known about the risk of horizontal transmission from an immunocompromised host with HBV reactivation. We treated two children with fulminant hepatitis B and acute hepatitis B, respectively, whose grandmother, an HBV carrier, had been undergoing rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R+CHOP) therapy for lymphoma. The grandmother was also suffering from fulminant hepatitis when both children became ill. The complete HBV DNA sequences of the three family members were identical. The full genome sequence analysis of HBV provided strong evidence of intrafamilial transmission of HBV. Treatments that cause immunosuppression, such as R+CHOP therapy for lymphoma, can increase the levels of serum HBV DNA and the risk of intrafamilial HBV infection when given to HBV carriers. In conclusion, specific antiviral prophylaxis is indispensable for preventing horizontal transmission as well as reactivation of HBV in chemotherapy-treated HBV carriers.

Ultrasonographic diagnosis of juvenile colonic polyps.

To reduce the risks of air-contrast barium enemas and colonoscopy, we studied the use of saline enemas for ultrasonographic examination of children with rectal bleeding. Thirty-nine children, from 2 years 8 months to 8 years 3 months of age, were examined. Juvenile colonic polyps were ultrasonographically demonstrated and histologically confirmed in 25 children; all the polyps were solitary and pedunculated, and were located in the splenic flexure in 3 children, the descending colon in 6, the sigmoid colon in 12, and the rectum in 4. Ultrasonographic findings by hydrocolonic ultrasonography were identical to those obtained by immersion ultrasonography of removed specimens. Hypoechoic areas within more hyperechoic polyps were shown histologically to be dilated glandular canals. The 14 children in whom no abnormal ultrasonographic findings were shown had no further rectal bleeding after resuming regular defecation, and 5 of these 14 had negative colonoscopic findings. No adverse reactions were noted in any child during or after the saline enema examination. We conclude that ultrasonographic examination with a saline enema is a safe and accurate method of assessing children with rectal bleeding, especially for the diagnosis of juvenile colonic polyps.

Fasting and bed rest, even for a relatively short period, are risk factors for ceftriaxone-associated pseudolitiasis.

Cholelithiasis is one of the side‐effects of ceftriaxone (CTRX). Reportedly, the cholelithiasis resolves relatively soon after cessation of CTRX, hence, it is called pseudolithiasis. Previous reports have suggested that biliary pseudolithiasis can cause not only gallstone attacks, but also severe adverse events, such as cholecystitis and pancreatitis. The purpose of this study was to prospectively elucidate the risk factors and clinical features of CTRX‐associated pseudolithiasis in pediatric patients.