Impacts of Perinatal Dioxin Exposure on Motor Coordination and Higher Cognitive Development in Vietnamese Preschool Children: A Five-Year Follow-Up.

Dioxin concentrations remain elevated in the environment and in humans residing near former US Air Force bases in South Vietnam. Our previous epidemiological studies showed adverse effects of dioxin exposure on neurodevelopment for the first 3 years of life. Subsequently, we extended the follow-up period and investigated the influence of perinatal dioxin exposure on neurodevelopment, including motor coordination and higher cognitive ability, in preschool children. Presently, we investigated 176 children in a hot spot of dioxin contamination who were followed up from birth until 5 years old. Perinatal dioxin exposure levels were estimated by measuring dioxin levels in maternal breast milk. Dioxin toxicity was evaluated using two indices; toxic equivalent (TEQ)-polychlorinated dibenzo-p-dioxins/furans (PCDDs/Fs) and concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Coordinated movements, including manual dexterity, aiming and catching, and balance, were assessed using the Movement Assessment Battery for Children, Second Edition (Movement ABC-2). Cognitive ability was assessed using the nonverbal index (NVI) of the Kaufman Assessment Battery for Children, Second Edition (KABC-II). In boys, total test and balance scores of Movement ABC-2 were significantly lower in the high TEQ- PCDDs/Fs group compared with the moderate and low exposure groups. NVI scores and the pattern reasoning subscale of the KABC-II indicating planning ability were also significantly lower in the high TCDD exposure group compared with the low exposure group of boys. However, in girls, no significant differences in Movement ABC-2 and KABC-II scores were found among the different TEQ-PCDDs/Fs and TCDD exposure groups. Furthermore, in high risk cases, five boys and one girl highly exposed to TEQ-PCDDs/Fs and TCDD had double the risk for difficulties in both neurodevelopmental skills. These results suggest differential impacts of TEQ-PCDDs/Fs and TCDD exposure on motor coordination and higher cognitive ability, respectively. Moreover, high TEQ-PCDDs/Fs exposure combined with high TCDD exposure may increase autistic traits combined with developmental coordination disorder.

Successful treatment of plasma exchange for severe cerebral venous thrombosis with thyrotoxicosis.

Although cerebral venous thrombosis (CVT) is generally treated with anticoagulants, some patients have a poor prognosis. We report a 34-year-old woman who developed severe CVT with mental symptoms and intracerebral hemorrhage with central herniation. She had a hypercoagulable state accompanied by thyrotoxicosis. Aggressive medical therapies including unfractionated heparin, a mixture of concentrated glycerin and fructose, and intravenous administration of thiamazole, iohexol, and propranolol were ineffective. The patient was treated with plasma exchange (PE) two times, in addition to aggressive medical therapies. The neurologic symptoms and laboratory data including high levels of thyroid hormones began to improve soon after the first PE. Activated partial thromboplastin time was prolonged after PE although the heparin dose was not changed. After 6 months, her modified Rankin Scale score was 2. PE should be considered for severe CVT as a result of a hypercoagulable state accompanied by thyrotoxicosis, because it not only reduces thyroid hormones, but also might remove multiple prothrombotic factors.

Transient directional disorientation as a manifestation of cerebral ischemia.

The authors describe 2 patients who presented with transient directional disorientation (TDD) as a manifestation of cerebral ischemia. The patients suddenly lost sense of direction in a familiar environment despite preserved ability to recognize landmarks, and recovered within a short time. Brain MRI revealed an ischemic lesion in the right medial occipital lobe and the corpus callosum in case 1 and in the right parieto-occipital sulcus (POS) in case 2. After ictus, fMRI study of a navigation task was performed, which demonstrated the activation of the POS unilaterally in case 1 and bilaterally in case 2. We propose that TDD of our patients is related to temporary dysfunction of bilateral POS.

Association between gastric atrophy and Helicobacter pylori infection in Japanese children: a retrospective multicenter study.

The purpose of this study was to determine whether Helicobacter pylori infection and mucosal inflammation result in gastric atrophy in Japanese children. A total of 196 patients ages 1-16 years were retrospectively studied: 131 patients were infected with H. pylori and 65 patients were uninfected. Antral (n = 196) and corpus biopsy specimens (n = 70) were investigated based on the Updated Sydney system. In both the antrum and corpus, H. pylori-infected patients showed significantly higher degrees of inflammation and activity of gastritis, compared with noninfected patients. The prevalence of grade 2 or 3 atrophy in the antrum was 10.7% in H. pylori-infected patients and 0% in the noninfected patients (P < .01) and in corpus 4.3% and 0%, respectively (P = .20). The frequency of intestinal metaplasia in the 2 study groups was 4.6% and 4.6% in the antrum and 0% and 4.2% in the corpus, respectively. Among H. pylori-infected patients, the antrum showed significantly higher degrees of H. pylori density, inflammation and activity of gastritis, and atrophy than the corpus. In the antrum, atrophy was significantly correlated with activity, whereas in the corpus, atrophy correlated with H. pylori density, inflammation, and activity. H. pylori-induced gastric inflammation can cause atrophy in Japanese children, predominantly in the antrum. It remains to be determined whether H. pylori-infected children with gastric atrophy are at increased risk for gastric cancer.

A family of Emery-Dreifuss muscular dystrophy with extreme difference in severity.

This report describes two patients, a father and son, with autosomal dominant Emery-Dreifuss muscular dystrophy. Although the father had the common phenotype, the son had a severe phenotype including early onset of weakness and fatal cardiomyopathy in childhood. Among the patients with severe phenotype of autosomal dominant Emery-Dreifuss muscular dystrophy, he is the first to have familial onset, and in the severe end of this disease spectrum.

Gastric epithelial cell turnover and mucosal protection in Japanese children with Helicobacter pylori infection.

BACKGROUND: In adults, epithelial cell proliferation and apoptosis of the gastric mucosa are induced by Helicobacter pylori infection and are associated with gastric atrophy or gastric carcinoma. In children, there are few studies about such epithelial changes. To elucidate the role of H. pylori infection in gastric mucosal inflammation, we immunohistochemically examined gastric mucosa of Japanese children. METHODS: Biopsy specimens obtained from the gastric antrum and corpus of H. pylori-infected (n = 13) and noninfected children (n = 15) were studied for immunolocalization of Ki-67, single-strand DNA, manganese superoxide dismutase (Mn-SOD), and CD68, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling. In 10 patients with successful eradication, pre- and posttreatment results were compared. RESULTS: In both gastric antrum and corpus, neutrophil and mononuclear cell infiltration, epithelial cell proliferation, and apoptosis significantly increased in H. pylori-infected patients, predominantly in the antrum. In the antrum of H. pylori-infected patients, there was positive correlation between the degrees of neutrophil infiltration and cell proliferation (P < 0.05) or apoptosis (P < 0.05). H. pylori eradication improved mucosal inflammation, cell proliferation (P < 0.001), and apoptosis (P < 0.01) in the antrum. Mn-SOD immunoreactivity and CD68-positive macrophages in the antrum, which significantly increased in H. pylori-infected patients, decreased after the eradication. CONCLUSIONS: H. pylori infection induced gastric mucosal inflammation and epithelial cell turnover in children. Moreover, gastric mucosal defense mechanism against H. pylori infection was activated. H. pylori eradication in childhood might prevent the accumulation of gastric epithelial cell damage.

Clinical course and prognosis of 27 patients with childhood onset multiple sclerosis in Japan.

To investigate whether outcomes of childhood onset multiple sclerosis (MS) have changed or not, the clinical courses of childhood onset MS in 27 patients at our hospital and those reported by Fukuyama in 1991 were compared. The ratios of our patients with poor prognosis in walking and vision were decreased. Widespread use of high-dose corticosteroid therapy and interferon therapy may be one cause of the low frequency of severe sequelae in our study.

Helicobacter heilmannii infection in a child after successful eradication of Helicobacter pylori: case report and review of literature.

An 11-year-old boy with Helicobacter pylori-associated duodenal ulcer was successfully treated with a combination of lansoprazole, amoxicillin, and clarithromycin. Endoscopy and gastric biopsies were repeated 2 and 12 months later, showing ulcer healing and eradication of H. pylori. However, a 3-year follow-up study demonstrated H. heilmannii in the antral mucosa based on its characteristic morphology and positive urease test and negative culture. The patient had no contact with domestic animals such as cats and dogs. A 7-day course with lansoprazole, amoxicillin, and clarithromycin was performed again, resulting in successful eradication of the organism. Pediatric cases with H. heilmannii infection reported are reviewed.

Multicenter comparison of rapid lateral flow stool antigen immunoassay and stool antigen enzyme immunoassay for the diagnosis of Helicobacter pylori infection in children.

BACKGROUND AND AIM: The stool antigen enzyme immunoassay (EIA) methods are widely used for diagnosing Helicobacter pylori infection. Recently, a novel, rapid stool antigen test, the lateral flow immunoassay (LFI) method, has been developed. The primary purpose of this study was to compare the EIA method with the LFI method for the diagnosis of H. pylori infection in children. MATERIALS AND METHODS: Stool specimens from children being evaluated for H. pylori infection were also examined using the LFI (ImmunoCard STAT! HpSA) and EIA methods (Premier Platinum HpSA). The sensitivity, specificity and accuracy of the test were based on the 13C-labeled urea breath test. RESULTS: One hundred and eighty-two children and adolescents, 3-17 years of age (mean 9.2 years), were studied. In addition, 29 patients who received eradication therapy were re-evaluated 2 or 3 months post-treatment. The 13C-labeled urea breath test was positive in 64 patients (35.2%). The sensitivity, specificity and accuracy of the LFI method were 90.6% (95% CI = 80.7-96.5%), 95.8% (92.1-99.4%), and 94.0% (90.5-97.4%), respectively and for the EIA method, sensitivity, specificity and accuracy were 96.8% (95% CI, 89.0-99.6%) and 99.2% (97.5-100%), and 98.3% (96.5-100%), respectively. There were no significant differences in results among the age groups 3-5, 6-10 and 11-17 years. As for the assessment of H. pylori eradication, the results of the LFI and EIA methods agreed with those of 13C-urea breath test in 27/29 and 29/29 patients, respectively. CONCLUSIONS: The LFI stool antigen method showed a good sensitivity, specificity and accuracy for diagnosing H. pylori infection in children. This novel method may be useful in clinical practice as an office-based test because it is rapid, reliable and easy to perform.

Dystonia in a 13-year-old boy with secondary progressive multiple sclerosis.

We report a patient who developed relapsing-remitting multiple sclerosis (MS) at 8 years old, and then had a progressive clinical course and dystonia. Dystonia of the patient is probably due to a lesion of the basal ganglia. Abnormal posture or movement disorder is very rarely found in MS, and progressive clinical course is also rare in childhood. The patient is worthy of attention because of his childhood onset, progressive clinical course and dystonia.

The prevalence of Helicobacter pylori in Japanese children with gastritis or peptic ulcer disease.

BACKGROUND: Although Helicobacter pylori infection is typically acquired in childhood, the role of H. pylori infection in gastroduodenal diseases in childhood remains to be defined. The purpose of this study was to evaluate the prevalence of H. pylori infection in children with gastritis, duodenal ulcer, and gastric ulcer. METHODS: This was a retrospective analysis of 283 Japanese children (mean age, 11.5 years) with non-nodular gastritis ( n = 73), nodular gastritis ( n = 67), duodenal ulcer ( n = 100), and gastric ulcer ( n = 43). H. pylori status was based on biopsy tests. Clinical symptoms at the time of endoscopy were analyzed with regard to a possible association with the infection. RESULTS: The prevalence of H. pylori in non-nodular gastritis, nodular gastritis, duodenal ulcer, and gastric ulcer was 28.8%, 98.5%, 83.0%, and 44.2%, respectively. H. pylori was significantly linked to duodenal ulcer and gastric ulcers in the age group of 10-16 years, but not in the age group of 9 years and under. In children with H. pylori infection, nodular gastritis was observed in 26.3% of gastric ulcer patients and in 74.7% of duodenal ulcer patients ( P < 0.001). H. pylori infection was significantly associated with the prevalence of anemia ( P < 0.05). CONCLUSIONS: H. pylori is the most important causal factor for the development of duodenal ulcer in childhood. While H. pylori infection appears to be a risk factor in gastric ulcer, other causes are responsible for most cases. Nodular gastritis is the most common type of H. pylori gastritis in childhood. Chronic infection with H. pylori is associated with anemia.

[A case of myeloradiculitis as a complication of visceral larva migrans due to Ascaris suum].

A 35-year-old man noticed a tingling sensation and subsequent slight weakness in the distal part of the left lower extremities, which extended to the left thigh over the following 8 months, when he developed a urinary disturbance. He was admitted to a local hospital and diagnosed as having myelitis, because of the presence of a gadolinium (Gd)-enhanced lesion in the lumbar spinal cord corresponding to the tenth thoracic vertebra (Th10) level. The symptoms disappeared along with some residual sensory disturbance following intravenous administration of 1 g of methylprednisolone (IVMP) for 3 days. However, 4 months later, the patient gradually developed gait disturbance, dysuria, impotence, and fecal incontinence, and was admitted to our hospital in May 2001. A neurological examination revealed the presence of myeloradiculopathy causing a slight weakness in the left hamstring muscles, with positive Babinski and Lasegue signs on the same side. In addition, deep tendon reflexes were absent in the 4 extremities and vibration sense was moderately decreased in the lower extremities, though the results of electrophysiological tests of motor and sensory nerves were normal. A magnetic resonance imaging (MRI) study showed a Gd-enhanced lesion in the spinal cord at the Th8-9 vertebrae level, which was 1 to 2 vertebrae above the initially detected lesion. A lumbar puncture yielded cerebrospinal fluid (CSF) containing mononuclear cells at 7/mm3 that were comprised of an increasd number of CD4+CD25+ activated helper T cells; however, no myelin basic protein or oligoclonal IgG band was present. Serological examinations were negative for the presence of collagen/vascular disorders as well as viral infection due to CMV, EBV, HSV, VZV, and HTLV-1, however, positive for specific antibodies against Ascaris suum in both serum and the CSF, confirming the diagnosis of chronic myeloradiculitis due to visceral larva migrans. The patient was first treated with a single course of a daily 600-mg dose of oral albendazole for 4 weeks, which was resulted in restoration of muscle weakness, as well as disappearance of the Lasègue sign. However, in contrast to the clinical improvement, the CSF sample obtained immediately after completing the treatment showed a worsening trend, as the CSF cell count had increased with a manifestation of marked eosinophilia and CD4+CD25+ cells were also increased. Thereafter, 3-day IVMP treatment was performed twice in cojunction with 3 courses of oral albendazole therapy for the subsequent 4 months, which resulted in normalization of all laboratory measurements concerning the CSF along with a decrement trend in serum and CSF antibody titers specific to Ascaris suum. Our results suggest that neurological involvement due to visceral larva migrans can be efficaciously treated with not only helminthic drugs but also intravenous corticosteroids.

Effect of Helicobacter pylori infection on gastric acid secretion and meal-stimulated serum gastrin in children.

BACKGROUND: Comparative studies of gastric acid secretion in children related to Helicobacter pylori infection are lacking. The purpose of this study was to compare acid secretion and meal-stimulated gastrin in relation to H. pylori infection among pediatric patients. MATERIALS AND METHODS: Thirty-six children aged 10-17 years (17 with H. pylori infection) undergoing diagnostic endoscopy participated in the study. Diagnoses included gastritis only (n = 23), duodenal ulcer (n = 5) and normal histology (n = 8). Gastric acid output was studied using the endoscopic gastric secretion test before and 2-3 months after H. pylori eradication. Meal-stimulated serum gastrin response was assessed before and 12 months after eradication. RESULTS: H. pylori gastritis was typically antrum-predominant. Acid secretion was greater in H. pylori-positive patients with duodenal ulcer than in gastritis-only patients or controls [mean +/- standard error (SE): 6.56 +/- 1.4, 3.11 +/- 0.4 and 2.65 +/- 0.2 mEq/10 minutes, respectively; p <.001]. Stimulated acid secretion was higher in H. pylori-positive boys than girls (5.0 +/- 0.8 vs. 2.51 +/- 0.4 mEq/10 minutes, respectively; p <.05). Stimulated acid secretion pre- and post-H. pylori eradication was similar (5.47 +/- 0.8 vs. 4.67 +/- 0.9 mEq/10 minutes, respectively; p =.21). Increased basal and meal-stimulated gastrin release reversed following H. pylori eradication (e.g. basal from 134 to 46 pg/ml, p <.001 and peak from 544 to 133 pg/ml, p <.05). CONCLUSIONS: H. pylori infection in children is associated with a marked but reversible increase in meal-stimulated serum gastrin release. Gastric acid hypersecretion in duodenal ulcer remains after H. pylori eradication, suggesting that the host factor plays a critical role in outcome of the infection.

Immunoglobulin A enteropathy: a possible variant of Henoch-Schönlein purpura.

This study calls attention to a new syndrome presenting with gastrointestinal symptoms including abdominal pain, vomiting, and/or hematemesis and endoscopic multiple lesions predominantly in the descending duodenum, without the skin rash observed in Henoch-Schonlein purpura. We examined the gastrointestinal mucosa for IgA deposits in nine children and compared the results with those for three patients with Henoch-Schönlein purpura. In addition, gastroduodenal biopsy specimens of 11 patients with various diseases were studied as controls for IgA staining. Intestinal histology showed nonspecific mucosal inflammation without vasculitis. In six patients without rash (67%), IgA deposition was observed in the capillary wall with the same staining pattern as seen in two patients with Henoch-Schonlein purpura. Compared with the controls (9%), the positive rate of IgA deposition was significantly higher in nonrash patients (P < 0.01). Deposited IgA showed immunoreactivities of polymeric IgAl containing J chain. IgA deposits were ultrastructually seen along the plasma membranes of the endothelial cells. Overall, the data suggest that IgA deposition played a pathogenetic role in the gastrointestinal damage in this group of patients presenting primarily with gastrointestinal complaints. Further studies are needed to clarify whether this patient population has a variant of Henoch-Schönlein purpura or a distinct "IgA enteropathy."

[Immunologic therapy for secondary and primary progressive multiple sclerosis].

Immunological treatments of progressive multiple sclerosis are discussed. Recent trials of interferon-beta 1b(IFN beta-1b) and IFN beta-1a in secondary progressive MS (SPMS) have demonstrated treatment benefits on relapse rate and accumulation of MRI lesions, and one trial of IFN beta-1b showed significant slowing of disability progression. In another recent study, mitoxantrone, a potent immunosuppressive agent, was reported to reduce progression of disability in SPMS. As regards primary progressive MS, there is currently no convincing disease-modifying treatment. Pathologic studies have revealed that axonal injury is prominent in MS and may be the explanation for irreversible disability. It is hoped that therapeutic strategies will be aimed at axonal loss as well as inflammation and demyelination.

A newly developed small-caliber videoduodenoscope for endoscopic retrograde cholangiopancreatography in children.

BACKGROUND: In neonates and younger children, the procedure of endoscopic retrograde cholangiopancreatography (ERCP) is now optimally performed using a small-caliber fiberoptic duodenoscope. However, there have been no reports on a specially designed videoduodenoscope for pediatric ERCP. GOAL: To evaluate performance and clinical usefulness of a newly developed small-caliber videoduodenoscope for ERCP in children. STUDY: We have developed a side-viewing videoduodenoscope with a 8.0-mm outside diameter of the tip and a 2.0-mm diameter instrument channel (Olympus PJF-240). In a total of 10 pediatric patients aged 11 months to 15 years (mean age, 6.1 years) who underwent ERCP using this videoduodenoscope, its feasibility was evaluated. Clinical diagnoses included pancreatitis (n = 4), choledochal cyst (n = 3), sclerosing cholangitis (n = 1), cholecystitis (n = 1), and choledocholithiasis (n = 1). In all patients, ERCP was done in the standard fashion under general anesthesia. RESULTS: ERCP was successful in 9 of 10 patients (90%). In the procedure, entering the descending duodenum was smooth and positioning the papilla on the endoscopic image was proper. In an 11-month-old infant, extraction of biliary stones by endoscopic balloon dilation was successfully done. Post-ERCP complications, including a significant increase of serum amylase levels, were not reported in any patients. CONCLUSION: This new videoduodenoscope has a potential for ERCP in all age groups of children.

Relationship of bladder dysfunction to lesion site in multiple sclerosis.

PURPOSE: We investigated the relationship of voiding dysfunction type and the lesion site in patients with multiple sclerosis. MATERIALS AND METHODS: Voiding dysfunction was evaluated in 32 patients with multiple sclerosis using the International Prostate Symptom Score and urodynamic tests. Lesion sites were determined by combined neurological examination and magnetic resonance imaging findings. RESULTS: Compared with reports from Western countries the ratio of emptying-to-filling symptoms was high in Japan. Of urinary symptoms only filling correlated with disability status and disease duration. Urinary symptoms were not related to lesion sites. Urodynamic evaluation revealed detrusor hyperreflexia in 14 of 32 patients, hyporeflexia or areflexia in 12, detrusor hyperreflexia with impaired contractile function in 4, a low compliance bladder in 1 and normal function in 1. Of 14 patients with hyperreflexia 13 had overactive sphincter concurrently. Incompetent sphincter was identified in 2 patients who had detrusor hyperreflexia with impaired contractility and in 1 with a low compliance bladder. A significant correlation was noted for a pontine lesion and detrusor hyporeflexia, and for a cervical cord lesion and detrusor-sphincter dyssynergia. CONCLUSIONS: Detrusor hyporeflexia and detrusor-sphincter dyssynergia are indicative of a pontine and cervical spinal cord lesion, respectively. Thus, the lesion site in the central nervous system may be a major determinant of the type of bladder and urethral sphincter dysfunction. The high prevalence of emptying symptoms in Japanese patients may reflect the prevalence of detrusor hyporeflexia and detrusor-sphincter dyssynergia.

Accuracy of the stool antigen test for the diagnosis of childhood Helicobacter pylori infection: a multicenter Japanese study.

OBJECTIVE: The (13)C-urea breath test (UBT) has been accepted as a reliable noninvasive test for detecting Helicobacter pylori infection. Recently, another noninvasive test, a new enzyme immunoassay for H. pylori antigens in stool, has been widely investigated for its clinical usefulness. The purpose of this multicenter study was to evaluate the diagnostic accuracy of the stool antigen test in Japanese children. METHODS: A total of 264 children (148 male and 116 female; mean age 9.2 yr, range 2-17 yr) who underwent (13)C-UBT and the stool antigen test were studied. The diagnosis in these patients was gastritis (n = 49), gastric ulcer (n = 4), duodenal ulcer (n = 24), recurrent abdominal pain (n = 43), and other conditions (n = 144). The stool antigen test was performed using the HpSA ELISA (Premier Platinum HpSA, Meridian Diagnostics). According to manufacturer's instructions, an absorbance at 450/630 nm of <0.100, > or =0.120, and 0.100-0.119 was defined as negative, positive, and indeterminate, respectively. Based on the (13)C-UBT with a cutoff value of 3.5 per mil, the performance of HpSA was studied. In 21 patients who received eradication therapy, the HpSA was performed at baseline and at 1, 2, and 6 months after completion of therapy. Eradication of H. pylori was confirmed by (13)C-UBT at 2 or 3 months of follow-up. RESULTS: (13)C-UBT showed that 76 children were infected with H. pylori and 188 were not infected. In these same children, HpSA results were positive in 77 children, negative in 183, and indeterminate in four. The overall sensitivity, specificity, and accuracy of the test were 96.0% (95% CI = 88.6-99.2%), 96.8% (95% CI = 94.2-99.3%), and 96.5% (95% CI = 94.3-98.8%), respectively. There were no significant differences in these results among age groups of < or =5, 6-10, and > or =11 yr. Receiver operating characteristic curve analysis demonstrated that the best cutoff value of absorbance at 450/630 nm was 0.110. When a single cutoff value of 0.110 without indeterminate results was used, the sensitivity, specificity, and accuracy were 96.1% (95% CI = 90.8-99.7%), 96.3% (95% CI = 93.6-99.0%), and 96.2% (95% CI = 93.9-98.5%), respectively. In 19 patients in whom H. pylori was successfully eradicated, HpSA results were negative at 1 month of follow-up and remained negative through 6 months. CONCLUSIONS: The HpSA is an accurate test for the detection of H. pylori infection in all age groups of children.

Diagnostic accuracy of the 13C-urea breath test for childhood Helicobacter pylori infection: a multicenter Japanese study.

OBJECTIVES: In adults, the 13C-urea breath test (UBT) has been widely used as a noninvasive test of Helicobacter pylori infection because of its high sensitivity and specificity. However, this test is less well established in pediatric practice. The optimum cutoff value and test protocol of the 13C-UBT remains to be established in the pediatric population. The primary purpose of this study was to evaluate diagnostic accuracy of the 13C-UBT for children and to determine its optimum cutoff value. METHODS: A total of 220 Japanese children aged 2-16 yr (mean = 11.9) who underwent upper GI endoscopy and gastric biopsies were finally studied. Endoscopic diagnoses included gastritis (n = 131), gastric ulcer (n = 15), duodenal ulcer (n = 72), and combined ulcer (n = 2). H. pylori infection status was confirmed by biopsy tests including histology, urease test, and culture. With the 13C-UBT, breath samples were obtained at baseline and at 20 min after ingestion of 13C-urea without a test meal and were analyzed by isotope ratio mass spectrometry. Based on biopsy tests, a cutoff value was determined using a receiver operating characteristic curve. In 26 children (seven children infected and 19 noninfected), paired breath samples were also measured by nondispersive infrared spectometry (NDIRS). RESULTS: Biopsy tests demonstrated that 89 children (40%) were infected with H. pylori and 131 children were not infected. There were no statistical differences in mean delta 13C values at 20 min between male and female H. pylori-infected and noninfected patients. A receiver operating characteristic analysis defined the best cutoff value as 3.5 per thousand. The overall sensitivity and specificity at a cutoff value of 3.5 per thousand were 97.8% (95% CI = 92.1-99.7%) and 98.5% (95% CI = 96.4-100%), respectively: high sensitivity and specificity were demonstrated in all three age groups (< or =5, 6-10, and > or = 11 yr). There was a close correlation between the values with isotope ratio mass spectrometry and NDIRS methods (r = 0.998, p < 0.001). CONCLUSIONS: The 13C-UBT with a cutoff value of 3.5 per thousand is an accurate diagnostic method for active H. pylori infection. The test with the NDIRS method is inexpensive and might be widely applied in clinical practice.