False positive of an immunochromatography kit for detection of norovirus in neonatal feces.

Norovirus was detected in the feces from five neonates in the growing care unit by a rapid immunochromatography (ICG) kit. However, confirmation using reverse transcription polymerase chain reaction (RT-PCR), RT-loop-mediated isothermal amplification (RT-LAMP), and nested RT-PCR methods showed negative results from all the feces. In addition, the ICG test for the detection of norovirus was positive for four cases out of the 16 feces from other asymptomatic neonates/infants. Only one feces out of the four samples was positive by RT-LAMP. In this study, among the factors related to false positives with the norovirus ICG kit, there were no differences regarding the commencement of feeding, nutrition, and sample collection methods. Since the false positive rate of ICG in the diagnosis of norovirus infection in neonates and early infancy is high, ICG is not an appropriate method, and it is necessary to confirm the results using reliable methods like RT-PCR.

Two cases of partial dominant interferon-γ receptor 1 deficiency that presented with different clinical courses of bacille Calmette-Guérin multiple osteomyelitis.

We experienced two cases of unrelated Japanese children with bacille Calmette-Guérin (BCG) multiple osteomyelitis with partial interferon (IFN)-γ receptor 1 (IFNGR1) deficiency. Heterozygous small deletions with frame shift (811 del4 and 818 del4) were detected, which were consistent with the diagnosis of partial dominant IFNGR1 deficiency. Case 1: a 2-year-old boy visited us because of limb and neck pain. He had been vaccinated with BCG at 17 months of age. Multiple destructive lesions were observed in the skull, ribs, femur, and vertebral bones. Mycobacterium bovis (BCG Tokyo 172 strain by RFLP technique) was detected in the bone specimen. The BCG multiple osteomyelitis was treated successfully without recurrence. Case 2: an 18-month-old girl developed multiple osteomyelitis 9 months after BCG inoculation. Radiologic images showed multiple osteolytic lesions in the skull, ribs, femur, and vertebrae. M. bovis (BCG Tokyo 172 strain) was detected in the cultures from a bone biopsy. Her clinical course showed recurrent osteomyelitis and lymphadenitis with no pulmonary involvement. The effects of high-dose antimycobacterial drugs and IFN-γ administration were transient, and complete remission has since been achieved by combination antimycobacterial therapy, including levofloxacin. Partial dominant IFNGR1 deficiency is a rare disorder, but it should be considered when a patient presents with multiple osteomyelitis after BCG vaccination. The cases that are resistant to conventional regimens require additional second-line antituberculous drugs, such as levofloxacin.

A severe form of epidermal nevus syndrome associated with brainstem and cerebellar malformations and neonatal medulloblastoma.

Here we report a boy with epidermal nevus syndrome associated with brainstem and cerebellar malformations and neonatal medulloblastoma. The patient had epidermal nevi and complicated brain malformations including macrocephaly with polymicrogyria, dysmorphic and enlarged midbrain tectum, enlarged cerebellar hemispheres with small and maloriented folia. The patient died after surgical resection of medulloblastoma which was newly recognized on MRI at 51 days of age. Postmortem pathological examinations showed very unique and bizarre malformation of the midbrain and hindbrain. The cerebellar cortex exhibited a coarse, irregular and bumpy surface, blurred border between the Purkinje cell layer and internal granule cell layer, and many foci of heterotopia in the cerebellar white matter. The brainstem showed multiple anomalies, including enlargement of superior colliculi, hypoplasia of pyramidal tracts and dysplasia of inferior olivary nuclei. The unusual constellation of brain malformations of our patient will widen the spectrum of epidermal nevus syndrome.

Brainstem disconnection associated with nodular heterotopia and proatlantal arteries.

We report on a patient with brainstem disconnection associated with periventricular nodular heterotopia and bilateral proatlantal intersegmental arteries. The patient was a girl born after 37 weeks of gestation with birth weight of 1,938 g. Polyhydroamnios and lack of swallowing movement were noted on fetal ultrasonography. No spontaneous body movement or respiration was observed after birth, whereas facial movement was preserved. She had marked generalized weakness and absent deep tendon reflexes. She remains alive and hospitalized at 4 years of age but requires mechanical ventilation and feeding through a gastrostomy tube. MRI showed absence of the lower pons and the medulla oblongata associated with hypoplasia of the cerebellar vermis and hemispheres. In addition, ventriculomegaly and periventricular nodular heterotopia were observed in the cerebrum. MR angiography demonstrated the absence of vertebral arteries and presence of bilateral proatlantal intersegmental arteries arising from the external carotid arteries. Array-comparative genomic hybridization analysis did not show any genomic copy number aberrations. No mutation was found in the FLNA gene or the EN2 gene. The constellation of the malformations of our patient suggested that genes related to the development of the central nervous and vascular system may be involved in the pathogenesis of brainstem disconnection.

Studies of anti-inflammatory effects of Rooibos tea in rats.

BACKGROUND: Rooibos tea is known to be caffeine free with abundant flavonoids. Aspalathin and nothofagin, the main flavonoids contained in Rooibos tea, have stronger anti-oxidative activity than other flavonoids. As oxidative stress can induce inflammation, the anti-inflammatory effects of Rooibos tea were investigated using a rat colitis model. METHODS: Seven-week-old Wister rats were divided into two groups: one group given Rooibos tea, and one given water. After four weeks of breeding, serum superoxide dismutase (SOD) levels were determined using the Electron Spin Resonance analysis. Urine 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations were also determined as reflections of DNA damage using enzyme-linked immunosorbent assay. Furthermore, rats were administrated dextran sodium sulfate (DSS), which is known to induce colitis in rodents, with or without Rooibos tea to evaluate its anti-inflammatory activity. Clinical symptoms, hemoglobin, serum iron and SOD levels were compared between the groups. RESULTS: There were no significant differences in bodyweight gain or laboratory data between the groups. The serum SOD levels were significantly increased, and urine 8-hydroxy-2'-deoxyguanosine levels were significantly decreased in the Rooibos group compared with the controls (P < 0.05 in each). After DSS administration, the serum SOD levels were significantly higher in the Rooibos group compared to the controls (P < 0.05). As a result, a decreased hemoglobin level, observed in the control group, was prevented in the Rooibos group after the DSS challenge. CONCLUSION: Rooibos tea may prevent DNA damage and inflammation by its anti-oxidative activity in vivo. As Rooibos tea is free from caffeine, routine intake may be safe and useful in reducing oxidative stress in children.

Evaluation of psychosomatic stress in children by measuring salivary chromogranin A.

AIM: To investigate the usefulness of salivary chromogranin A (CgA) and cortisol as stress markers, and the effects of distraction on the suppression of stress in children. METHODS: We examined salivary CgA and cortisol responses before and after venipuncture in hospitalized children with and without distraction using a kaleidoscope. RESULTS: Salivary CgA levels immediately after venipuncture were significantly higher than those immediately before it, and at 60 min after venipuncture they were significantly lower than those immediately after it. However, salivary cortisol showed no significant differences at any of the three time points. In contrast, distracted by the kaleidoscope, there were no significant differences in salivary CgA and cortisol levels at all three time points. CONCLUSION: In children, salivary CgA level is a useful marker of stress. As an index of the effect of distraction, the measurement of salivary CgA is useful.

Bifidobacterium breve enhances transforming growth factor beta1 signaling by regulating Smad7 expression in preterm infants.

OBJECTIVES: Transforming growth factor (TGF) beta1 displays a broad spectrum of activities in mucosal regulation, including induction of oral tolerance, potent anti-inflammatory effects, mucosal IgA expression and effects on epithelial cell proliferation and differentiation. The present study examined the effect of probiotics on the immunologic system of preterm infants in relation to TGF-beta signaling. METHODS: Subjects comprised 19 preterm infants divided into 2 groups: receiving Bifidobacterium breve supplementation (B. breve group) and without supplementation (controls). Blood samples were collected from both groups on days 0, 14 and 28 after birth. Serum cytokine levels were measured using enzyme-linked immunosorbent assay, and expression levels of the TGF-beta signaling molecule, Smad, were examined using semiquantitative reverse transcriptase-polymerase chain reaction. RESULTS: Serum TGF-beta1 level was elevated on day 14 and remained elevated on day 28 in the B. breve group. Level of messenger RNA expression was enhanced for Smad3 and reduced for Smad7 (antagonistic Smad) after B. breve administration relative to levels in controls on day 28. CONCLUSIONS: These results demonstrated that the administration of B. breve to preterm infants can up-regulate TGF-beta1 signaling and may possibly be beneficial in attenuating inflammatory and allergic reactions in these infants.

Factors involved in the regulation of plasma leptin levels in children and adolescents with anorexia nervosa.

OBJECTIVE: The effects of changes in body mass index (BMI) and other factors on plasma leptin levels in children and adolescents with anorexia nervosa (AN) were examined. METHODS: Plasma leptin levels and BMI was measured before and after initiation of refeeding therapy every 2 weeks for 8 weeks in 12 children and adolescents with AN. The plasma levels of insulin, cortisol, insulin-like growth factor-I (IGF-I), and tumor necrosis factor-alpha (TNF-alpha) were also measured in these subjects before and after 8 weeks of the refeeding therapy, and the results were compared with those from 12 age-matched healthy girls. RESULTS: The plasma leptin and IGF-I levels, as well as the BMI, in the AN patients before refeeding therapy were significantly lower than both of these indices in the AN patients 8 weeks after initiation of the therapy and in the controls. The plasma leptin levels and BMI in the AN patients 8 weeks after initiation of the therapy were still significantly lower than those in the controls. Significant correlations between the plasma leptin levels and BMI were detected in the AN patients both before and 8 weeks after initiation of the refeeding therapy, as well as in the controls. The BMI showed a significant increase beginning at 2 weeks after initiation of the therapy compared with that before refeeding, but the plasma leptin levels did not significantly increase until 4 weeks after the initiation of therapy. CONCLUSION: The results suggest that plasma leptin levels reflect changes in body fat content in children and adolescents with AN, although there is a delay in the recovery of plasma leptin levels compared with those of BMI in the early period of refeeding therapy, which is probably regulated by other factors.

Resting energy expenditure and plasma leptin levels in adolescent girls with anorexia nervosa.

OBJECTIVE: Our aim was to examine the relationship between resting energy expenditure (REE) and circulating leptin levels during long-term refeeding in adolescent girls with anorexia nervosa (AN). METHOD: We measured REE, the plasma leptin level, the free T(3) level, body surface area (BSA), and dietary energy intake in AN adolescents before and 8 weeks after refeeding therapy. RESULTS: All parameters in AN subjects before the refeeding therapy were significantly lower than those in AN subjects after the therapy and in the controls. There were no significant differences in REE and BSA between posttherapy AN subjects and controls, but plasma leptin levels in the posttherapy AN subjects were still significantly lower than those in the controls. Significant correlations between REE and BSA were detected in the AN subjects both before and after the refeeding therapy, but REE did not correlate significantly with plasma leptin level in either of the AN groups. DISCUSSION: Our results suggest that the REE in AN subjects after long-term refeeding therapy is not associated with the changes in plasma leptin levels but with BSA.