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Long-term nocturnal enuresis treatment leads to stress and lowered self-esteem for children and their parents. This study evaluated the short-term effectiveness and safety of vibegron 50 mg for children with refractory nocturnal enuresis.A retrospective cohort study of children with therapy-resistant enuresis was conducted using data for July 2019 through December 2019. Enuresis frequency was recorded during 30 days before and after additional vibegron administration with prior treatment. We assessed the treatment effectiveness based on enuresis frequencies between before and after treatment with vibegron 50 mg. Statistical evaluation was performed using a paired t-test.Among 29 children receiving vibegron, 14 (48.3%) exhibited partial or complete response to vibegron. Enuresis frequencies were, respectively, 15.8 ± 9.2 (± SD) and 9.5 ± 9.6 (± SD) before and after treatment with vibegron during the observed 30 days. Statistically significant reduction in enuresis frequency was found (p 0.001). Moreover, maximum morning urine of 200 ± 62.9 mL (± SD) before treatment with vibegron changed to 232 ± 76.6 mL (± SD) after treatment. Significant increase in voiding volume in the early morning was found (p 0.05). No drug-related severe adverse event was found.Short-term treatment with vibegron is safe and effective for children with refractory enuresis.

Neonatal diabetes mellitus (NDM) is a very rare disorder and its diagnosis can be challenging especially in mild and transient cases. Herein, we describe a 2.4-kg female infant born at 38 wk of gestation who showed hyperglycemia (388 mg/dL) on Day 1. Intermittent blood sampling showed glucose concentrations of 100–150 mg/dL on Day 2–5. However, continuous glucose monitoring (CGM) from Day 7 revealed hyperglycemia (> 200 mg/dL) after every feeding. The patient required low-dose (0.1–0.2 U/kg/d) insulin therapy for a short period (7 d). During the treatment, hypoglycemic (< 50 mg/dL) events were not detected by real- time CGM. Follow-up CGM from Day 32 showed normoglycemia for 3 full days; therefore, we ascertained that the diabetes had been transient. Later genetic analysis revealed an abnormal methylation pattern on chromosome 6q24, which is the most frequent cause of transient NDM. Most cases of 6q24-related NDM relapse after puberty, implying that long term follow up is required. We speculate that the NDM in this case might not have been diagnosed without CGM. This report highlights the usefulness of CGM for the initial diagnosis, monitoring during insulin therapy, and confirmation of improvement in patients with transient NDM.

Maternal–fetal transport of calcium (Ca2+) is important for bone mineralization in fetal development. Insufficient Ca2+ transport causes transient neonatal hyperparathyroidism (TNHP). Transient receptor potential cation channel, subfamily V, member 6 (TRPV6), has been found to play an important role in the active transport of Ca2+ through the placenta. Recently, TRPV6 gene was found to be the gene responsible for TNHP with severe skeletal undermineralization. To date, only seven cases of TNHP caused by TRPV6 recessive mutations have been reported. We present a case of TNHP caused by TRPV6 gene mutations. A female newborn was hospitalized because of respiratory distress. Marked undermineralization of the skeleton was observed in X-ray imaging. Laboratory examination revealed markedly high PTH and absence of hypercalcemia along with vitamin D deficiency. Her twin brother presented with almost no symptoms. Maternal laboratory findings indicated normocalcemia, but vitamin D deficiency with a high PTH level for the lactation period was observed. We initially diagnosed the patient as having secondary hyperparathyroidism because of maternal vitamin D deficiency. Nevertheless, the reasons underlying the discordant clinical manifestations between the twin siblings remained unclear. Our analysis of TRPV6 gene clarified that the patient had compound heterozygote mutations, which were reported previously (p.Ile223Thr and p.Gly428Arg). Pathologic mutations in TRPV6 gene were not detected in the other sibling. The clinical symptoms in the patient were transient: they resolved during infancy. TNHP caused by TRPV6 gene mutations is a unique disease in terms of its transient pathology in utero and relief after birth.

The effect of the side-wall ribs on the heat transfer and flow characteristics in the blade internal cooling passage was conducted by both experiments and CFD calculations, and its optimal shape, arrangement and further development were investigated. It is necessary for the side-wall ribs to optimize the shape for the purpose of not increasing the total pressure loss as much as possible. In this study, Λ and V shaped side-wall ribs with aspect ratio of 1.0 were numerically and experimentally investigated. In addition, with the aim of reducing the total pressure loss, the side-wall ribs with slit which were modified by removing the central part of the Λ and V shaped ribs and those combinations were investigated. As a result, it was confirmed that the combination of V and V shaped with slit were promising and multi-objective optimization using a genetic algorithm was conducted for it. The design parameters were the angle of attack (AoA) for both V shaped with slit and V shaped side-wall ribs, the slit width of V shaped and the height of ribs. The objective functions were Nusselt number, total pressure loss coefficient and thermal performance. The optimized shape has the highest thermal performance, although there exists a strong trade-off relationship between heat transfer coefficient and total pressure loss coefficient. Moreover, the effect of aspect ratio was investigated with considering the vortices distributions in the three-dimensional space. In this study, two kinds of aspect ratio, W/H=0.5 and 2.0 were numerically investigated. As a result, it was found that W/H=0.5 is the best with respect to thermal performance due to pressure loss reduction because the interaction of vortices were suppressed. In conclusion, the side-wall ribs promote the reattachment of separated cooling air flow and the high heat transfer coefficient region can be expanded and the thermal performance can be improved.

We describe a term infant who experienced recurrent apnea associated with intracranial hemorrhage and later, developed colonic perforation. Plasma protein C activity was below detectable limits and a heterozygous PROC mutation was identified. Neonatal colonic perforation is rare, and this case report highlights the importance of considering congenital Protein C deficiency.

Mycotic pulmonary artery aneurysms (MPAAs) are rare and life-threatening with currently no recommended treatment strategies. In this report, we describe a successfully treated case of ventricular septal defect in an 11-month-old girl who developed bacteremia, infective endocarditis, and MPAA caused by methicillin-resistant Staphylococcus aureus (MRSA). We first started vancomycin, gentamycin, and panipenem-betamipron for infective endocarditis but switched to teicoplanin and arbekacin on day 3 after initiating treatment because bacteremia persisted, and vancomycin minimum inhibitory concentration was relatively high at 2 mg/L. Although we added clindamycin on day 5 and fosfomycin on day 7, MRSA bacteremia persisted, and we finally added daptomycin at 10 mg/kg per day on day 8, whereupon the bacteremia subsided within a day. Although the bacteremia subsided, the patient developed septic pulmonary embolisms and septic arthritis on her left knee. We continued daptomycin but switched the concomitant drug to linezolid, trimethoprim-sulfamethoxazole, and rifampicin on day 11. After several repeats of puncture and lavage of her knee joint, she became afebrile on day 16. Computed tomography scans taken on day 32 revealed right pulmonary artery MPAAs. She was treated with long-term multidrug therapy, and MPAAs were absent on subsequent computed tomography scans on day 184. Multidrug therapy mainly based on daptomycin could be a possible salvage therapy for refractory MRSA bacteremia with high vancomycin minimum inhibitory concentration. Conservative treatment should be selectively considered as a treatment option for clinically stable MPAA instead of surgical and endovascular treatment.

Recently, the number of gas turbine combined cycle plants is rapidly increasing in substitution of nuclear power plants. The turbine inlet temperature (TIT) is constantly being increased in order to achieve higher effectiveness. Therefore, the improvement of the cooling technology for high temperature gas turbine blades is one of the most important issue to be solved. In a gas turbine, the main flow impinging at the leading edge of the turbine blade generates a so called horseshoe vortex by the interaction of its boundary layer and generated pressure gradient at the leading edge. The pressure surface leg of this horseshoe vortex crosses the passage and reaches the blade suction surface, driven by the pressure gradient existing between two consecutive blades. In addition, this pressure gradient generates a cross-flow along the endwall. This all results into a very complex flow field in proximity of the endwall. For this reason, burnouts tend to occur at a specific position in the vicinity of the leading edge. In this research, a methodology to cool the endwall of the turbine blade by means of film cooling jets from the blade surface and the endwall is proposed. The cooling performance is investigated using the transient thermography method. CFD analysis is also conducted to investigate the phenomena occurring at the endwall and calculate the film cooling effectiveness.

A previously healthy 2-year-old girl, vaccinated for varicella at 17 months, was admitted because of left-sided facial herpes zoster caused by vaccine-strain varicella-zoster virus (VZV). She recovered fully with no complication after intravenous treatment using acyclovir. Earlier reports have described that herpes zoster (HZ) rashes caused by vaccine-strain VZV tend to occur on the dermis corresponding to the skin area where the varicella vaccine was received. However, rashes appeared on this girl only in the trigeminal nerve area, which is unrelated to the vaccinated site. Results underscore the importance of distinguishing vaccine-strain VZV from wild-type VZV whenever encountering HZ cases after vaccination, even in immunocompetent children, irrespective of the skin lesion site. Monitoring vaccine-strain HZ incidence rates is expected to elucidate many aspects of varicella vaccine safety.

Background We previously reported on three preterm infants with blood glucose abnormalities after reaching full enteral feeding. Recently, it has been shown that clinically stable preterm infants may have large fluctuations in blood glucose after the establishment of enteral nutrition. We hypothesized that intraday glucose fluctuation is a common finding in preterm infants, but improves at term post-conceptual age. This report describes a case series. Methods From June 2010 to July 2012, 13 preterm infants (29.5 ± 2.1 post-conceptual weeks, 1144 ± 319 g) were enrolled in this study. Continuous glucose monitoring (CGM) was conducted on average at 33.5 ± 1.4 post-conceptual weeks, when they received gastric tube feeding every 3 h in the absence of i.v. glucose supply. Results Eight infants (62%) had large intraday glucose fluctuation with repeated hyperglycemic (>150 mg/dL) and hypoglycemic (

Introduction Bacterial meningitis may relapse after adequate antibiotic treatment. In most cases, however, the pathophysiology cannot be identified. Presentation of case We describe a preterm infant with recurrent episodes of meningitis due to infection with an identical Escherichia coli strain both at birth and at 10 days after cessation of a 3 week course of appropriate antibiotic treatment. At the time of recurrence, the patient presented with fulminant severe cardiac failure due to acute myocarditis, coupled with a concurrent echovirus 18 infection (confirmed by stool culture and serological analysis). Conclusion Co-infection by echovirus may underlie recurrence of Escherichia coli meningitis in this case.

Rationale Acute idiopathic pulmonary hemorrhage (AIPH) in infants is a rare condition, and a clear treatment protocol has not yet been established. Patient concerns We report 2 infant cases of AIPH in a 3-month-old male and a 1-month-old female, who presented at an emergency room with epistaxis and respiratory distress. Both were immediately intubated, which revealed a bloody intratracheal aspirate. Diagnosis Pulmonary hemorrhage was confirmed by X-ray and computed tomography imaging in both cases. The extensive evaluation revealed no specific etiology for the acute pulmonary hemorrhage, and AIPH was therefore diagnosed in both cases. Interventions Intravenous methylprednisolone resulted in a rapid improvement in oxygenation and a reduction in high airway pressure during mechanical ventilation. Methylprednisolone was subsequently tapered off within 13 and 3 days in cases 1 and 2, respectively. In case 1, intratracheal administration of a surfactant also resulted in an immediate improvement in respiratory condition and the patient was extubated after 2 days; no effect was seen in case 2, and the patient was extubated after 10 days. Outcome Both infants recovered well without sequelae or further relapse after 23 and 71 months of follow-up, respectively. Lessons Early administration of corticosteroid therapy and intratracheal administration of diluted surfactant should be considered for severe acute pulmonary hemorrhage in infants.

Background In neonatal resuscitation, laryngeal mask airway (LMA) is recommended when both face mask ventilation and endotracheal intubation fail. Experience of LMA among obstetricians, nurses and midwives in Japan, however, is limited. The aims of the present study were to (i) offer an LMA training course to professionals dealing with low-risk pregnancies at institutions across Japan; and (ii) assess the subsequent use and value of LMA at the participating institutions. Methods Between August 2016 and March 2017, a total of 18 training courses for 60 min were provided for around 350 medical personnel from 51 institutes. LMA use over the subsequent 12 months was assessed via a postal questionnaire. Results After training, a total of 38 institutes introduced LMA. Of 13 254 live births, seven cases of rescue use LMA in "cannot ventilate, cannot intubate" situations were reported. None of these seven newborns had any malformation of the upper airway. LMA insertion resulted in adequate ventilation in all seven cases. Conclusion LMA can be a life-saving tool in neonatal resuscitation. All medical institutions dealing with low-risk pregnancies in Japan should be equipped with this device.

Background: Small for gestational age and birth asphyxia are associated with neonatal transient hyperinsulinism (THI). Some newborns with THI showed marked erythroblastosis on admission to our neonatal intensive care unit. Objective: This study was designed to test our hypothesis that fetal erythroblastosis may be a risk factor for developing THI. Methods: The records of all babies admitted to our neonatal intensive care unit within 24 h of birth between January 2010 and May 2014, and who were born after 34 weeks of gestation, were retrospectively reviewed. Hyperinsulinism was diagnosed as hypoglycemia concomitant with high serum insulin in babies requiring >6 mg/kg/min intravenous glucose and THI as hyperinsulinism without maternal diabetes or genetic disorders. The following three possible risk factors for THI were evaluated: (1) birth weight z-score, (2) 1-min Apgar score and (3) absolute nucleated red blood cell (aNRBC) count on admission. Results: Of 705 infants, 8 were diagnosed with THI. Multivariate logistic regression analysis revealed that the aNRBC count was the most significant risk factor for THI. The median aNRBC count was 181/µl (interquartile range 0-538/µl), and 8 of 71 infants (11.3%) having an aNRBC count >1,413/µl (90th percentile in this study) had THI. The aNRBC counts in the 8 cases with THI were significantly higher than those in the 5 cases with hyperinsulinism caused by maternal diabetes or genetic disorders. Conclusions: This study showed that the aNRBC count was strongly associated with subsequent THI. Fetal erythroblastosis, characterized by chronic fetal hypoxia, may be an indicator of perinatal stress sufficient to cause THI.

Background: Forkhead box G1 gene ( FOXG1 ) mutations and deletions are associated with a congenital variant of Rett syndrome (RTT). Nucleotide alterations of the coding region of FOXG1 have never caused dysmorphic features. Patient: An 8-year-old boy with the congenital variant of RTT who showed severe psychomotor deterioration, epilepsy, acquired microcephaly, and involuntary movements including jerky movements of the upper limbs and tongue protrusion. He showed dysmorphic features including round face, anteverted nostrils, and tented upper lips. Brain magnetic resonance imaging showed hypoplasia of the frontal lobes and the rostral part of the corpus callosum. The molecular cytogenetic analysis confirmed a de novo deletion of 14q12 including FOXG1 in this patient. Conclusion: We identified the smallest deletion of 14q12 involving FOXG1 among those previously reported. Dysmorphic facial features are a characteristic for the patients with chromosomal deletion including FOXG1 . In our patient, C14orf23 is the only transcript other than FOXG1 . Therefore, C14orf23 might be responsible for facial dysmorphism.

Background: Neonatal toxic shock syndrome-like exanthematous disease (NTED) and toxic shock syndrome (TSS) are both caused by the bacterial superantigen, toxic shock syndrome toxin-1 (TSST-1), which is mainly produced by methicillin-resistant Staphylococcus aureus (MRSA). However, the coincidence of NTED and maternal TSS has yet to be reported. Cases: A 4-day-old full-term infant showed a typical clinical profile and laboratory findings that matched the criteria for the diagnosis of NTED, resulting in complete remission after 7 days. Fever and a skin rash were observed in the mother of the infant 3 days postpartum. In both cases, marked expansion and activation of Vβ2+ T cells in the peripheral blood was confirmed by flow cytometry. Anti-TSST-1 antibody was not detected in the mother nor in the infant. Conclusion: Obstetricians should consider TSS for the differential diagnosis of puerperal fever and systemic erythema if the infant develops NTED.

Dumping syndrome is infrequently reported, but known to occur after Nissen fundoplication in children. However, it may be difficult both to diagnose and manage. Here we presented four infants who received Nissen fundoplication for severe gastroesophageal reflux disease, two of whom developed dumping syndrome whilst the other two did not. Continuous glucose monitoring (CGM) was very useful to clearly detect large glycemic fluctuation around each feeding. CGM was also helpful to prove the effect of treatment to avoid abnormal glucose levels. We believe that dumping syndrome in children may be underdiagnosed if clinicians rely solely on the recognition of symptoms or limited frequency of blood samplings. CGM might be the most sensitive diagnostic tool.

Late-onset hypoglycemia (day 12-16, blood glucose

Background SCN1A is the gene that codes for the neuronal voltage-gated sodium-channel alpha-subunit 1. It is generally considered that an SCN1A truncating mutation causes the severe phenotype of Dravet syndrome. Patients We describe 11- and 4-year-old male patients presenting with mild Dravet syndrome with a truncating mutation of SCN1A. The former patient showed moderate mental retardation; however, seizure was controlled to almost one incident a year by levetiracetam and topiramate. Carbamazepine was also effective, which is atypical of Dravet syndrome. The latter patient showed a borderline developmental quotient and did not have episodes of afebrile seizure. Conclusion Two patients presented with mild Dravet syndrome, even though they had a truncating mutation of SCN1A. Not all truncating mutations of SCN1A cause the severe phenotype of Dravet syndrome.

Immunization of health care personnel (HCP) is critically important to reduce healthcare-associated influenza infections substantially. During 2009-2010, 74% of all HCP at Kitano Hospital, Osaka, Japan, including 94% of pediatricians, received the monovalent unadjuvanted influenza A (H1N1) pdm09 vaccine. We evaluated the vaccine's immunogenicity. Sixteen pediatricians received 15 μg hemagglutinin antigen subcutaneously. Antibody titer assays were conducted using hemagglutination-inhibition antibody assay on days 0 and 21, and at 5 mo after vaccination. Seroprotection rates, seroconversion rates, and geometric mean titer folds at 21 d were, respectively, 43.8%, 43.8%, and 5.4 in all subjects, 70.0%, 70.0%, and 8.0 in subjects aged 27-34 y, and 0.0%, 0.0%, and 8.0 in subjects aged ≥ 35 y. None of the latter group met the European Medicines Agency criteria. We hope to adopt intradermal routes and further the development of the influenza vaccine using new technology to improve immunogenicity in Japan.

Familial hemophagocytic lymphohistiocytosis (FHL), which typically has its onset during infancy, is uniformly fatal if not treated. It therefore requires prompt therapeutic intervention. Although hyperferritinemia has been emphasized as a useful marker for FHL, some nonfatal cases in infants with spontaneous remission also manifest with hyperferritinemia. However, distinguishing them is difficult because initial clinical features of these infants are similar. The authors encountered 14 infants with hyperferritinemia (serum ferritin >674 ng/mL), which normalized within 3 weeks following a benign clinical course. The authors compared the levels of HLA-DR+CD3+ T-cell subsets and interferon-gamma (IFN-γ) in the peripheral blood between these infants and FHL cases: one of the authors’ own patients and others from the literature. Serum IFN-γ was not detected in infants with hyperferritinemia. Moreover, levels of HLA-DR+CD3+ T cells were extremely depressed. In contrast, serum IFN-γ was elevated and HLA-DR+CD3+ ...

Despite frequent colonization with Mycoplasma hominis, the invasive disease is rare in neonates. This study describes a neonatal case with meningitis in which M. hominis was isolated from a cerebrospinal fluid sample by culture and detected by PCR. The M. hominis infection was confirmed by elevated metabolic inhibition titers against the isolated M. hominis strain and anti-M. hominis antibodies in serum samples. Minocycline and moxifloxacin were effective against M. hominis, which caused meningitis in the patient. However, the patient exhibited left hemiplegia because of massive brain infarction. Based on data of the previously reported 28 cases in addition to our case, the high morbidity and mortality of the M. hominis central nervous system infection were confirmed; it was assumed to result from delayed diagnosis and ineffective initial therapy. Early diagnosis and prompt initiation of appropriate antimicrobial treatment are necessary for a favorable prognosis. Fourth-generation fluoroquinolones, especially moxifloxacin, deserve wider use in such cases.

BACKGROUND X-linked recessive congenital nephrogenic diabetes insipidus (NDI) is caused by mutations of the arginine vasopressin type 2 receptor gene (AVPR2). More than 200 mutations of the AVPR2 gene with complete NDI have been reported although only 15 mutations with partial NDI has been reported to date. METHODS We herein report a Japanese kindred with partial NDI. The proband is an 8-year-old boy who was referred to our hospital for nocturnal enuresis. Water deprivation test and hypertonic saline test suggested partial renal antidiuretic hormone arginine vasopressin (AVP) resistance. RESULTS Analysis of genomic DNA revealed a novel missense mutation (p.L161P) in the patient. The patient's mother was heterozygous for the mutation. Three-dimensional (3-D) modeling study showed that L161P possibly destabilizes the transmembrane domain of the V2 receptor, resulting in its misfolding or mislocalization. CONCLUSIONS Distinguishing partial NDI from nocturnal enuresis is important. A clinical clue for diagnosis of partial NDI is an incompatibly high level of AVP despite normal serum osmolality.

We previously reported on three preterm infants with blood glucose abnormalities after reaching full enteral feeding. Recently, it has been shown that clinically stable preterm infants may have large fluctuations in blood glucose after the establishment of enteral nutrition. We hypothesized that intraday glucose fluctuation is a common finding in preterm infants, but improves at term post-conceptual age. This report describes a case series.From June 2010 to July 2012, 13 preterm infants (29.5 ± 2.1 post-conceptual weeks, 1144 ± 319 g) were enrolled in this study. Continuous glucose monitoring (CGM) was conducted on average at 33.5 ± 1.4 post-conceptual weeks, when they received gastric tube feeding every 3 h in the absence of i.v. glucose supply.Eight infants (62%) had large intraday glucose fluctuation with repeated hyperglycemic (150 mg/dL) and hypoglycemic (50 mg/dL) events. In five infants, follow-up CGM at 36-38 weeks post-conceptual age showed more stable glycemic changes without any abnormal glucose levels.On CGM, in some preterm infants intermittent tube feeding resulted in large intraday glucose fluctuation at 31-35 post-conceptual weeks, but the pattern disappeared before discharge (36-38 post-conceptual weeks).

A 44-day-old male infant with familial hemophagocytic lymphohistiocytosis (FHL) associated with the MUNC13-4 mutation is reported. He presented with fever and poor feeding, lymphocytosis with thrombocytopenia and CSF pleocytosis without virological explanation. On the basis of progressive hyperferritinemia (1323 ng/ml), anemia (hemoglobin: 5.2 g/dl), hypertriglyceridemia (547 mg/dl) and increased LDH (1063 IU/l) with hemophagocytosis in the bone marrow, hemophagocytic lymphohistiocytosis was diagnosed. He showed a good response to corticosteroid therapy and the disease was stable for more than 5 months. Thereafter, he suffered from central nervous system complications, and successfully underwent unrelated cord blood stem cell transplantation. A remission was observed for more than 2 years, with mild mental retardation. Genetic analysis revealed that he had a compound heterozygous mutation of MUNC13-4; namely a novel 2163G>A mutation resulting in W721X, and 754-1G>C resulting in a premature stop codon in this gene. Western blot analysis showed the complete loss of the MUNC13-4 protein, whereas other molecules associated with the SNARE systems were detected at normal levels. Conclusion. FHL may have a broad clinical spectrum, and further analysis on its phenotype-genotype association is required to establish an appropriate treatment strategy, including immunochemotherapy and stem cell transplantation in the future.

Herlitz junctional epidermolysis bullosa (H-JEB) is a hereditary bullous disease caused by absent expression of laminin-5, a component of anchoring filaments within the dermal-epidermal basement membrane zone. Affected individuals usually die during the first 1 year of life. We studied an infant with H-JEB who presented with nephrotic syndrome, a previously unreported complication that may contribute to early death in this disease. DNA analysis revealed a compound heterozygote for mutations 2379delG and Q995X in the LAMB3 gene. The patient had massive albuminuria, attributable to failure of the glomerular filtration barrier, and high urinary N-acetylglucosaminidase levels, indicating renal tubular involvement. Electron-microscopic examination of the renal tissue revealed diffuse fusion of the foot processes, irregular swelling of the lamina rara interna, and disappearance of endothelial cell fenestrations. Immunohistopathologic analysis of the patient’s renal tissue revealed compositional changes in laminin isoforms of the glomerular basement membrane and no detectable laminin-5 in the renal tubular basement membrane, which suggests that laminin-5 may play an important role in renal function. Our findings strongly suggest that H-JEB should be considered in the spectrum of congenital nephrotic syndromes. Combination therapy with meticulous skin care and treatment strategies established for congenital nephrotic syndromes may rescue patients with this disease.

To determine a more timely acquisition of accurate results for influenza patients, a rapid diagnostic testing for influenza were studied on 877 pediatric patients performed during the 2002-2003 flu season in our hospital. Of these, 337 patients were finally diagnosed as influenza based on the test results and treated with antiviral agents, amantadine or oseltamivir. Ten (29%) of the 34 patients whose tests were negative within 12 hours after onset became positive over 12 hours after onset. On the other hand, diagnoses based on antigen tests over 12 hours after onset were reliable because all 13 patients first confirmed negative were unchanged when tested afterward. These 10 patients missed the opportunity to take antivirals early, which possibly caused them to have significantly longer (p = 0.0003) febrile duration and higher frequency of admission (p < 0.0001) than the 106 patients first confirmed positive within 12 hours after onset. Days from onset until starting antivirals (mean 1.4 days), the febrile duration (mean 2.7 days) and frequency of hospitalization (20.5%) of the 219 patients who tested positive over 12 hours after onset were significantly worse (p < 0.0001, p < 0.0001 and p = 0.0406, respectively) than those of patients testing positive within 12 hours after onset (mean 0.2 days, mean 1.7 days and 11.3%, respectively). The febrile duration (mean 2.3 days) of the patients confirmed positive even over 12 hours, but within 48 hours, of onset was tolerable but significantly longer (p < 0.0001) than that of patients confirmed positive within 12 hours after onset. The frequency (19.6%) of hospitalization of the patients confirmed positive even over 12 hours, but within 48 hours, of onset was not significantly different from that of patients confirmed positive within 12 hours after onset. These results suggested that over 12 hours but within 48 hours after onset of illness is the best period for the rapid diagnosis to correctly determine whether a patient should be treated with antiviral agents based on the result.

This report describes a small-for-date extremely low birth weight infant who manifested bradycardic events, respiratory failure, and hemolytic jaundice during her first week of life. These complications were attributed to severe hypophosphatemia and hypokalemia. Inadequate supply and refeeding syndrome triggered by early aggressive parenteral nutrition were responsible for electrolyte abnormalities.

Background: The aim of this study was to determine the usefulness of the three-lead electrocardiogram (ECG) during neonatal resuscitation. Methods: Both pulse oximetry (PO) and ECG were applied immediately after delivery to measure heart rate (HR). We reviewed video recordings of the respective monitors, and checked the time at which each monitor started to display reliable rate values. Results: In 20 deliveries, ECG showed HR much earlier than PO (median 38 s vs 122 s after delivery). ECG displayed reliable HR throughout resuscitation. We were able to confirm the effectiveness of the initial respiratory support from the elevation in HR. Conclusions: ECG was a safe and reliable method for showing HR, and was used to determine the initiation and the effectiveness of resuscitation in the delivery room.

We describe an 8-year-old girl with the mildest form of acute necrotizing encephalopathy, associated with pandemic influenza A. She manifested a convulsion engendering deterioration of consciousness, although cranial computed tomography and magnetic resonance imaging within 4 hours after the convulsion revealed no abnormalities. Cranial magnetic resonance imaging 20 hours after the convulsion revealed lesions of the thalamus bilaterally, brainstem tegmentum, internal capsule, and white matter. She was diagnosed with acute necrotizing encephalopathy. Typically, the prognosis of acute necrotizing encephalopathy with a brainstem lesion is poor. Nevertheless, she recovered almost completely, after early intervention with pulsed methylprednisolone and high-dose γ-globulin therapy. She manifested a thermolabile phenotype of carnitine palmitoyltransferase II variants such as cystine-isoleucine-methionine phenotype type 9 (FVM-CIM; Phe352Cys-Val388Ile-Met647Met alleles), resulting in a predisposition to encephalopathy during influenza infection. This case is the first, to the best of our knowledge, of pandemic influenza A-associated acute necrotizing encephalopathy with a good outcome despite severe magnetic resonance imaging findings.

Acute encephalopathy in childhood is frequently associated with common infections, especially in East Asia. Various types have been identified although many cases remain unclassified. Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease presenting impairment of cortisol biosynthesis. We report three CAH children with acute infection-related encephalopathy. They exhibited disturbed consciousness or seizures, which did not improve after glucocorticoid administration, accompanied by clinical and laboratory findings of adrenal insufficiency. Brain MRI disclosed various patterns of white matter lesions, suggesting different types of acute encephalopathy such as clinically mild encephalitis/encephalopathy with a reversible splenial lesion or hemiconvulsion-hemiplegia syndrome. Acute encephalopathy should be considered and brain MRI immediately performed when impairment of consciousness does not improve after intravenous glucocorticoid administration in CAH patients. Further research is required to elucidate the epidemiology and pathogenic mechanisms of acute encephalopathy in CAH.

Three-lead electrocardiography and expired CO2 monitoring were used during positive pressure ventilation of seven non-intubated newborns (gestational age, 31-37 weeks; birthweight, 1503-2885 g). In all cases, adequate CO2 (15 mmHg) was detected prior to the achievement of stable heart rate (100 beats/min). The delay between detection of adequate CO2 and improvement of bradycardia ranged from 8 to 73 s (median, 15 s). Inadequate expired CO2 during positive pressure ventilation indicates airway obstruction or poor aeration of the newborn lungs. Thus, positive expiratory CO2 can be the first recognizable sign of successful ventilation during neonatal resuscitation.

Simultaneous presence of hemolytic anemia and bilirubin UDP-glucuronosyltransferase deficiency is a possible cause of misdiagnosis. Seven-year-old and 17-year-old brothers and a 15-year-old sister consecutively suffered from aplastic crises. Although few spherocytes were present, the siblings and their mother had diagnoses of hereditary spherocytosis with flow cytometric analysis of eosin-5'-maleimide-labeled red blood cells in addition to osmotic fragility test. However, inappropriately high values of bilirubin compared with mild hemolysis persisted. Further analysis of UDP-glucuronyltransferase 1A1 revealed all 3 siblings were heterozygous for A(TA)7TAA-P229Q. We report here the importance of careful evaluation of mild hereditary spherocytosis masking UDP-glucuronyltransferase 1A1 deficiency.

Bruton's tyrosine kinase (Btk) plays crucial roles in B cell differentiation as well as mast cell activation through the high-affinity IgE receptor (Fc∊RI). Defects in the btk gene lead to agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Mast cells from xid and btk null mice exhibit mild defects in degranulation and severe impairments in the production of proinflammatory cytokines upon Fc∊RI cross-linking. Recent studies demonstrated the role of Btk in a sustained increase in intracellular calcium concentrations in response to antigen receptor stimulation. Btk is also involved in the activation of stress-activated protein kinases, JNK/SAPK1/2, and thereby regulates c-Jun and other transcription factors that are important in cytokine gene activation. Regulation of the JNK/SAPK activation pathway by Btk may be related to the proapoptotic function of Btk in the programmed cell death in these hematopoietic cells. J. Leukoc. Biol. 65: 286–290; 1999.