Takashi Ishige

SRD5B1 gene analysis needed for the accurate diagnosis of primary 3‐oxo‐Δ4‐steroid 5β‐reductase deficiency

Background and Aim:  We encounter hyper‐3‐oxo‐Δ4 bile aciduria in patients with severe cholestatic liver disease or fulminant liver failure during the neonatal period. However, simply by bile acid analysis, it is difficult to distinguish hyper‐3‐oxo‐Δ4 bile aciduria from primary 3‐oxo‐Δ4‐steroid 5β‐reductase deficiency.

In vivo recording of colonic motility in conscious rats with deficiency of interstitial cells of Cajal, with special reference to the effects of nitric oxide on colonic motility.

BackgroundWe recorded in vivo colonic motility in rats with a deficiency of interstitial cells of Cajal (ICC) (Ws/Ws rats) and in wild-type rats (+/+ rats), with special reference to the effects of nitric oxide (NO) on colonic motility in both types of rats, in order to ascertain the role of ICC in colonic motility, and the relationship between NO and ICC in regard to colonic motility.MethodsMiniature strain-gauge force transducers were sutured on the surface of the ascending and sigmoid colon of Ws/Ws rats and +/+ rats as controls. After 1 week and a fasting period of 24 h, colonic motility in +/+ and Ws/Ws rats was recorded. We also studied the effect of NO on colonic motility in both types of rats, by means of the administration of N-nitro-l-arginine methyl ester (l-NAME) or l-arginine.ResultsIn +/+ rats, there were contractions with high amplitude and long duration in both the ascending and sigmoid colon. The number, amplitude, and duration of contractions in the ascending colon were 9.9/20 min, 6.1 g, and 22.7 s, respectively. These findings in the sigmoid colon were 5.2/20 min, 5.2 g, and 23.0 s, respectively. The number of contractions in the ascending and sigmoid colon in Ws/Ws rats (2.3 and 1.0/20 min) was significantly lower than that in +/+ rats (P < 0.05). The number of contractions in the ascending and sigmoid colon in +/+ rats (9.7 and 5.1/20 min before treatment) was significantly increased by l-NAME administration (28.7 and 13.9/40–60 min after treatment; P < 0.05), but that in Ws/Ws rats was not influenced. The number of contractions in the ascending and sigmoid colon in +/+ rats (10.2 and 5.2/20 min before treatment) was significantly decreased by l-arginine administration (3.6 and 2.1/40–60 min after treatment; P < 0.05), but that in Ws/Ws rats was not influenced.ConclusionsICC must be related to the occurrence of a normal number of colonic contractions. NO may be involved in the inhibitory regulation of colonic motility, and the effect of NO on the occurrence of contractions appears to be mediated by ICC.

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.

A role for fosfomycin treatment in children for prevention of haemolytic–uraemic syndrome accompanying Shiga toxin-producing Escherichia coli infection

The role of antimicrobial therapy for Shiga toxin-producing Escherichia coli (STEC) infection has not been clearly defined. A prospective study identified antibiotic use as a significant risk factor for subsequent development of haemolytic-uraemic syndrome (HUS). However, early treatment with fosfomycin, a bacteriostatic antibiotic, resulted in a significantly decreased risk of HUS. The aim of this study was to evaluate a role of fosfomycin therapy in the development of HUS in children who contracted STEC infection. The study included 118 children who contracted a STEC infection between 1997 and 2013. A pre-defined questionnaire was utilised to collect patient information regarding age, sex, presenting symptoms (fever, abdominal pain, diarrhoea and bloody stool), results of stool culture examination, initial results of white blood cell counts and C-reactive protein (CRP), use of antibiotics, the timing of introduction of antibiotics, and complications including HUS. Of the 118 patients, 64 were diagnosed with HUS and the remaining 54 did not develop HUS. Multivariate analysis showed that three independent factors (age, initial values of CRP and use of fosfomycin) were significantly associated with the occurrence of HUS; of particular note, the adjusted odds ratio for use of fosfomycin was 0.15 (95% confidence interval 0.05-0.45). Use of fosfomycin within the first 5 days of illness may decrease the development of STEC-related HUS in children.

Endoscopic findings in the acute phase of food protein-induced enterocolitis syndromae

1. Klinnert MD, Robinson JL. Addressing the psychological needs of families of foodallergic children. Curr Allergy Asthma Rep 2008: 8: 195–200. 2. Cummings AJ, Knibb RC, King RM, Lucas JS. The psychosocial impact of food allergy and food hypersensitivity in children, adolescents and their families: a review. Allergy 2010: 65: 933–45. 3. Muraro A, Werfel T, HoffmannSommergruber K, et al. EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy. Allergy 2014: 69: 1008–25. 4. Kelsay K. Psychological aspects of food allergy. Curr Allergy Asthma Rep 2003: 3: 41–6. 5. Polloni L, Toniolo A, Lazzarotto F, et al. Nutritional behavior and attitudes in food allergic children and their mothers. Clin Transl Allergy 2013: 3: 41. 6. Lau G-Y, Patel N, Umasunthar T, et al. Anxiety and stress in mothers of foodallergic children. Pediatr Allergy Immunol 2014: 25: 236–42. 7. MacKenzie H, Roberts G, Van Laar D, Dean T. Teenagers’ experiences of living with food hypersensitivity: a qualitative study. Pediatr Allergy Immunol 2010: 21: 595–602. 8. Akeson N, Worth A, Sheikh A. The psychosocial impact of anaphylaxis on young people and their parents. Clin Exp Allergy 2007: 37: 1213–20. 9. Manassis K. Managing anxiety related to anaphylaxis in childhood: a systematic review. J Allergy 2012: 2012: 316296. 10. DunnGalvin A, Gaffney A, Hourihane JO. Developmental pathways in food allergy: a new theoretical framework. Allergy 2009: 64: 560–8. 11. Munoz-Furlong A. Daily coping strategies for patients and their families. Pediatrics 2003: 111(Supp. 3): 1654–61. 12. Muraro A, Polloni L, Lazzarotto F, et al. Comparison of bullying of food-allergic versus healthy schoolchildren in Italy. J Allergy Clin Immunol 2014: 134: 749–51.

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

Abstract:  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 × 109/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.

Temporal Trend of Pediatric Inflammatory Bowel Disease: Analysis of National Registry Data 2004 to 2013 in Japan

Increased incidence and prevalence of pediatric inflammatory bowel disease (IBD) have been reported in Western countries. Changes in the prevalence of pediatric IBD in Asian countries, however, remain unclear. We evaluated the changes in the prevalence of IBD among Japanese adults and children from 2004 to 2013, by using the Japanese national registry data of patients receiving financial aid. Data from children (ages 0-19 years) were compared with those from young adults (ages 20-39 years). In 2004, age-standardized prevalences of Crohn disease (CD) and ulcerative colitis (UC) among children were 4.2 of 100,000 and 11.0 of 100,000, respectively. The corresponding prevalences among young adults were 41.0 of 100,000 and 89.8 of 100,000, respectively. In 2013, age-standardized prevalences of pediatric CD and UC were 7.2 of 100,000 and 15.0 of 100,000, respectively. During this period, prevalence of pediatric CD increased by 73.8% among children and by 49.0% in young adults. The prevalence of UC increased by 45.0% among children, and by 73.7% among young adults.

The treatment with infliximab for pediatric Crohn's disease: Nationwide survey of Japan.

Childhood‐onset inflammatory bowel disease (IBD) is characterized by extensive intestinal involvement and rapid early progression. Infliximab (IFX), cyclosporin (CYA), and tacrolimus (FK506) are increasingly used to treat pediatric IBD; however, their long‐term effects and adverse events have not been properly investigated in pediatric patients. The aim of this study was to characterize the effects of these biologics and immunomodulators on pediatric IBD patients in Japan. Additionally, we assessed IFX use in pediatric patients with Crohns disease (CD).

Combination of postmortem mass spectrometry imaging and genetic analysis reveals very long-chain acyl-CoA dehydrogenase deficiency in a case of infant death with liver steatosis

CASE HISTORY A 3-month-old infant was found dead in his bed. A postmortem computed tomography (CT) scan suggested fatty attenuation in the liver parenchyma, but no other potentially fatal changes were found. To clarify the cause of death, a medicolegal autopsy was carried out. AUTOPSY FINDINGS Internal examination confirmed the presence of liver steatosis as well as hepatomegaly. There were no other significant findings including encephalitis or brain edema. MASS SPECTROMETRY ANALYSIS To clarify the mechanism underlying lipid accumulation in the liver, matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) analysis was conducted. This indicated a significant accumulation of C14:1 acylcarnitine in the liver of the deceased, suggesting very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. GENETIC ANALYSIS To find the cause of the VLCAD deficiency, genetic analysis of the responsible gene, acyl-CoA dehydrogenase, very long chain (ACADVL), was performed. This revealed two novel mutations that may have accounted for the disease. CONCLUSION A combination of these data revealed that the liver steatosis in this case might have been caused by VLCAD deficiency based on genetic mutations of ACADVL. Thus, the deceased might have been vulnerable to energy crisis and sudden infant death. The present findings show that MALDI-IMS analysis as well as genetic analysis can be useful for elucidating the cause of death.

A case of sudden unexpected infant death involving a homozygotic twin with the thermolabile CPT2 variant, accompanied by rotavirus infection and treatment with an antibiotic containing pivalic acid

We investigated a case of sudden unexpected death involving a 22-month-old male homozygotic twin infant. After both of the twins had suffered from gastroenteritis, one was found dead in his bed, but his brother survived and has since been healthy. Notably, only the deceased had been treated with an antibiotic containing pivalic acid, which may sometimes cause hypocarnitinemia. Postmortem computed tomography and medicolegal autopsy demonstrated severe liver steatosis, and subsequent genetic analysis revealed that the twin had the thermolabile variant of carnitine palmitoyl transferase 2 (CPT2). On the basis of these facts, we concluded that the cause of death had been fatty acid oxidation deficiency accelerated by an antibiotic containing pivalic acid and virus infection in this infant harboring the thermolabile genetic variant of CPT2. Although each factor alone was not fatal, their combination appeared to have resulted in sudden unexpected infant death.