Serum α-fetoprotein concentration in extremely low-birthweight infants.

BACKGROUND: Extremely low-birthweight infants (ELBWI) are at greater risk of developing hepatoblastoma than are normal-weight infants. Serum α-fetoprotein (AFP) plays an important role as a tumor marker in the diagnosis of hepatoblastoma, therefore the aim of this study was to determine the changes in serum AFP concentration after birth in ELBWI. METHODS: Data were obtained for infants born between January 2005 and March 2008 with birthweight <1000 g who were followed up at Gunma Children's Medical Center with clinical examinations, including monitoring of the development of hepatoblastoma. The relationship between serum AFP concentration and age was analyzed up to 730 days after birth. RESULTS: Overall, 95 serum AFP measurements were obtained from 23 infants 30-730 days of age, with gestational age 24-32 weeks, and birthweight 498-982 g. Log10 (AFP [ng/mL]) was significantly correlated with log10 (age [days]) (r = -0.961, P = 0.000, n = 95), with the following regression formula: log10 (AFP [ng/mL]) = 11.063 - 3.752 log10 (age [days]) (adjusted R2  = 0.923, n = 95). The standard error of the estimate, mean log10 (age [days]), and the sum of squares for log10 (age [days]) were 0.363, 2.503, and 10.579, respectively. CONCLUSIONS: A correlation was found between serum AFP concentration and age in ELBWI, and the 95%CI of serum AFP concentration was determined for ELBWI up to 2 years after birth.

Virus detection and cytokine profile in relation to age among acute exacerbations of childhood asthma.

BACKGROUND: Little information is available regarding eosinophil activation and cytokine profiles in relation to age in virus-induced bronchial asthma. We therefore explored the association between age, respiratory viruses, serum eosinophil cationic protein (ECP), and cytokines/chemokines in acute exacerbations of childhood asthma. METHODS: We investigated viruses in nasal secretions from 88 patients with acute exacerbation of childhood asthma by using antigen detection kits and/or RT-PCR, followed by direct DNA sequencing analysis. We also measured peripheral eosinophil counts, and the serum levels of ECP and 27 types of cytokines/chemokines in 71 virus-induced acute asthma cases and 13 controls. RESULTS: Viruses were detected in 71(80.7%) of the 88 samples. The three major viruses detected were rhinoviruses, RS viruses, and enteroviruses; enteroviruses were found to be dominant in patients aged ≥3 years. There was no change in the levels of rhinoviruses and RS viruses between the two age groups, defined as children aged <3 years and children aged ≥3 years. Serum concentrations of ECP, IL-5, and IP-10 were significantly elevated in virus-induced acute asthma cases compared with controls. Serum ECP values were significantly higher in patients with virus-induced asthma at age ≥3 years compared with those aged <3 years. Among the 27 cytokines/chemokines, serum IP-10 was significantly higher in virus-induced asthma in patients <3 years than in those ≥3 years. Serum ECP and IL-5 production correlated significantly with age, whereas serum IP-10 showed an inverse correlation with age. CONCLUSIONS: Age-related differences in cytokine profiles and eosinophil activation may be related to virus-induced acute exacerbations of childhood asthma.

Chronic mucocutaneous candidiasis caused by a gain-of-function mutation in the STAT1 DNA-binding domain.

Chronic mucocutaneous candidiasis (CMC) is a heterogeneous group of primary immunodeficiency diseases characterized by chronic and recurrent Candida infections of the skin, nails, and oropharynx. Gain-of-function mutations in STAT1 were very recently shown to be responsible for autosomal-dominant or sporadic cases of CMC. The reported mutations have been exclusively localized in the coiled-coil domain, resulting in impaired dephosphorylation of STAT1. However, recent crystallographic analysis and direct mutagenesis experiments indicate that mutations affecting the DNA-binding domain of STAT1 could also lead to persistent phosphorylation of STAT1. To our knowledge, this study shows for the first time that a DNA-binding domain mutation of c.1153C>T in exon 14 (p.T385M) is the genetic cause of sporadic CMC in two unrelated Japanese patients. The underlying mechanisms involve a gain of STAT1 function due to impaired dephosphorylation as observed in the coiled-coil domain mutations.

Problems with using total serum bilirubin as a criterion for phototherapy in extremely low-birthweight infants.

BACKGROUND: Despite the early use of phototherapy and exchange transfusion in premature infants based on total serum bilirubin (TSB), the reemergence of kernicterus has been reported. The aim of this study was to assess the validity of using TSB as the criterion for phototherapy in extremely low-birthweight infants (ELBWI). METHODS: We reviewed the medical charts of 43 ELBWI admitted to hospital between January 2009 and December 2010, and analyzed the relationship between TSB and unbound bilirubin (UB). RESULTS: No infant underwent exchange transfusion or developed acute bilirubin encephalopathy. There was a significant correlation between TSB and UB measured immediately before phototherapy during the first 7 days of life (r = 0.657, P < 0.001), but none thereafter (r = 0.120, P = 0.213). Thirty-seven percent of infants who underwent phototherapy during the first 7 days of life had suprathreshold USB but subthreshold TSB, whereas this rose to 97% thereafter. CONCLUSIONS: No correlation was observed between TSB and UB in ELBWI after the first 7 days of life, and almost all phototherapy sessions were initiated based on the UB criterion, even though TSB was below the accepted threshold. UB may be high if jaundice is evaluated solely on the basis of TSB.

Age at onset of asthma and allergen sensitization early in life.

BACKGROUND: Epidemiological evidence indicates that the age at onset of asthma and allergen sensitization in early life is decreasing in people from Western countries. To explore latent trends, we conducted a retrospective examination of the age at onset of asthma and specific IgE antibodies against inhalant allergens in Japanese asthmatic children. METHODS: We conducted a case series study of 103 consecutive children with atopic type of asthma (aged 2 years to 16 years, mean age 9.4 ± 3.4 years). Diagnoses of asthma and allergic rhinitis were defined according to Japanese guidelines. The onset of asthma and allergic rhinitis was also defined as any report of asthma and allergic rhinitis confirmed by a physician. Allergen sensitization was evaluated as specific serum IgE levels for 9 common inhalant allergens in peripheral blood. Atopic type of asthma was defined as a being positive for at least one aeroallergen. RESULTS: Mean age at asthma onset was 2.3 ± 1.9 years, which is slightly lower than that of previous reports, including those published in Japan. A high prevalence rate of up to 80% was found for perennial antigens including Dermatophagoides spp. and house dust, as reported previously. Notably, some of the children aged at 1 year tested positive for these allergens. CONCLUSIONS: The age at onset of asthma seems to be decreasing in comparison with previous reports. Furthermore, the age at onset of allergen sensitization against inhalant allergens appears to follow this trend.

Elevated macrophage inflammatory protein 1α and interleukin-17 production in an experimental asthma model infected with respiratory syncytial virus.

BACKGROUND: Respiratory syncytial virus (RSV) infection is associated with both the development and exacerbation of bronchial asthma. We examined eosinophil infiltration and the cytokine profiles of both airway and peripheral blood in antigen-sensitized mice infected with RSV to investigate the pathogenesis of exacerbations of asthma due to RSV infection. METHODS: Ovalbumin (OVA)-sensitized mice were challenged by OVA inhalation 3 times and then infected with RSV [10(5) TCID50 (50% of tissue culture infectious dose)/25 g body weight] or mock infection immediately after the last challenge. Animals from each group, namely, the control (PBS instead of OVA inhalation plus mock infection), RSV (PBS plus RSV), OVA (OVA plus mock) and OVA/RSV (OVA plus RSV) were analyzed. Analysis included evaluation of airway responsiveness to methacholine, pathological findings in the airway by hematoxylin and eosin (HE) and Luna staining, bronchoalveolar fluid (BALF) and peripheral leukocytes counts, and concentrations of multiple cytokines/chemokines in both BALF and serum. RESULTS: Airway responsiveness was significantly enhanced in the OVA and OVA/RSV groups compared with the control group. Levels of tissue and BALF eosinophils were higher in the OVA and OVA/RSV groups than in the RSV or control group. Significantly higher levels of macrophage inflammatory protein (MIP)-1α in BALF were observed in the OVA/RSV group compared with the 3 other groups. Production of serum IL-17 was also significantly elevated in the OVA/RSV group compared with the control or OVA group. CONCLUSIONS: These findings suggest that MIP-1α and IL-17 may play important roles in acute exacerbation of asthma induced by RSV in an animal model.

Feeding interval and postprandial intestinal blood flow in premature infants.

BACKGROUND: The feeding interval is an important factor in enteral feeding of premature infants. We investigated postprandial intestinal blood flow in stable very-low-birthweight infants fed at 2-h and 3-h intervals. METHODS: We used pulsed wave Doppler ultrasound to measure blood flow velocity of the superior mesenteric artery (SMA) before feeding and at 15, 30, 45, and 60 min after feeding. Measurements were made on the day of starting enteral nutrition (1 or 2 days of age), and at 3 and 5 days of age. A total of 21 studies were performed in seven infants fed every 2 h, and 54 studies were performed in 18 infants fed every 3 h. RESULTS: In infants fed every 2 h, SMA blood flow velocity increased from before feeding to 30 min after feeding and then decreased at 60 min after feeding. In infants fed every 3 h, SMA blood flow velocity increased after feeding, reaching a peak at 30 min. The correlation coefficients between the volume of milk per feed and the postprandial increase in time-averaged mean blood flow velocity were 0.398 (P = 0.074, n = 21) and 0.597 (P = 0.000, n = 54) in infants fed at 2-h and 3-h intervals, respectively. CONCLUSIONS: SMA blood flow velocity significantly increased after feeding in infants fed at 2-h and 3-h intervals. The volume of milk per feed might affect the postprandial increase in SMA blood flow velocity.

Complications of peripherally inserted central venous catheter in Japanese neonatal intensive care units.

BACKGROUND: The aim of this study was to investigate the incidence and risk factors of peripherally inserted central venous catheter (PICC)-related complications using a multicenter case survey. METHOD: A prospective cohort study was carried out by 19 neonatal intensive care units (NICUs) in Japan from February 2005 to March 2007. A total of 975 case records were collected. PICC-related complications including pericardial effusion/cardiac tamponade pleural effusion/ascites, catheter removal difficulties, catheter-related bloodstream infection (CR-BSI), and symptomatic catheter-related thrombosis were collected from case record forms. As for precautions during insertion, institutions were classified into three groups: those with maximum barrier precautions; standard precautions; and no specific precautions. RESULTS: PICC complications occurred in 27 cases (2.9%) among 946 PICC. The incidence was 1.6% for CR-BSI, and 0.1% for cardiac tamponade. CR-BSI rate per 1000 catheter-days was 1.1 with maximum barrier precautions at catheter insertion, 1.2 with standard precautions, and 1.8 with no specific precautions. Multiple logistic regression analysis showed that proximal placement (odds ratio [OR], 3.88; 95% confidence interval [CI]: 1.42-10.60, P = 0.008) and longer placement duration (OR, 1.35; 95%CI: 1.14-1.60, for each week, P = 0.0005) independently contributed to overall complications. CONCLUSION: The incidence of cardiac tamponade was rare in this multicenter prospective study. Longer duration and proximal placement may be risk factors for PICC complications. In this cohort, the CR-BSI rate was low irrespective of the degree of barrier precautions at insertion.

Hepatic parenchymal hemodynamics of cholangitis with portal trunk thrombus using contrast-enhanced ultrasonography with Sonazoid: delineation of so-called central and peripheral zonal differentiation by arrival-time parametric imaging.

We carried out contrast-enhanced ultrasonography using Sonazoid for a patient who had portal thrombosis due to choledocholith and cholangitis, and the video images were analyzed by an offline procedure using arrival-time parametric imaging. Colors were changed with the time course from red to orange, yellow, green, light blue, and blue, with the time the contrast agent reached the right hepatic artery as the starting point. The central part of the liver was primarily colored blue, and the peripheral part primarily yellowish-green. In other words, we confirmed the central and peripheral zonal differentiation observed in the arterial phase of dynamic computed tomography by color mapping image of arrival-time parametric imaging. Particularly, real-time changes in the hemodynamics of the hepatic parenchyma could be captured by color mapping image using arrival-time parametric imaging.

DNA methylation changes between relapse and remission of minimal change nephrotic syndrome.

BACKGROUND: DNA methylation of gene promoters is associated with transcriptional inactivation. Changes in DNA methylation can lead to differences in gene expression levels and thereby influence disease development. We hypothesized that epigenetics underlies the pathogenesis of minimal change nephrotic syndrome (MCNS). METHODS: Genome-wide DNA methylation changes between relapse and remission in monocytes (n = 6) and naive T helper cells (Th0s) (n = 4) isolated from patients with MCNS were investigated using the microarray-based integrated analysis of methylation by isochizomers (MIAMI) method. We confirmed the MIAMI results using bisulfite-pyrosequencing analysis. Expression analysis was performed using quantitative real-time PCR. RESULTS: Three gene loci (GATA2, PBX4, and NYX) were significantly less methylated in Th0s during relapse than in remission, compared to none in monocytes. In addition, the distance distribution from the regression line of all probes in MIAMI was significantly different between monocytes and Th0s. The mRNA levels of the three genes in Th0s were not significantly different between relapse and remission. CONCLUSIONS: Our results demonstrate that the change in DNA methylation patterns from remission to relapse in MCNS occurs predominantly in Th0s rather than in monocytes and suggest that epigenetic regulation in Th0s underlies the pathogenesis of MCNS.

Effects of prophylactic indomethacin on renal and intestinal blood flows in premature infants.

BACKGROUND: Prophylactic indomethacin reduces severe intraventricular hemorrhage and symptomatic patent ductus arteriosus in premature infants. The purpose of this study was to investigate the effects of prophylactic low-dose indomethacin on renal and intestinal blood flow. METHODS: Subjects were 19 extremely low-birthweight infants admitted to our hospital and enrolled in a multicenter randomized control trial to study the efficacy and complications of prophylactic low-dose indomethacin in the reduction of severe intraventricular hemorrhage and patent ductus arteriosus (indomethacin and placebo groups, ten and nine infants, respectively). We measured blood flow velocity in the right renal artery (right RA) and superior mesenteric artery (SMA) with pulsed Doppler ultrasound before and after the administration of the first dose of 0.1 mg/kg indomethacin or placebo. RESULTS: End-diastolic blood flow velocity (EDV) in the right RA and SMA increased significantly after the administration of indomethacin (P = 0.0414 and 0.0284, respectively), although the time-averaged mean blood flow velocity (TAV) did not change significantly in either artery. In the placebo group, the pre- and postadministration values for TAV and EDV in the right RA and SMA did not differ. Neither group showed a significant change in the relative vascular resistance (mean blood pressure/TAV) in the right RA or SMA. EDV in the left pulmonary artery was significantly reduced only after the administration of indomethacin (P = 0.0284). CONCLUSIONS: Prophylactic low-dose indomethacin increases the diastolic blood flow in the RA and SMA via a reduction in the ductal shunt volume, with no change in the regional vascular resistance.

Differential effects of corticosteroids on serum eosinophil cationic protein and cytokine production in rhinovirus- and respiratory syncytial virus-induced acute exacerbation of childhood asthma.

BACKGROUND: Little information is available on eosinophil activation and the cytokine profile in virus-induced acute exacerbation of bronchial asthma; therefore, we examined the effects of treatments that included systemic corticosteroids on serum eosinophil cationic protein (ECP) and 17 cytokines/chemokines in rhinovirus- and respiratory syncytial (RS) virus-induced acute exacerbation of childhood asthma. METHODS: We measured the peripheral eosinophil count, as well as the serum levels of ECP and 17 types of cytokines/chemokines (IL-1ß, 2, 4, 5, 6, 7, 8, 10, 12, 13, and 17 and IFN-γ, TNF-α, GM-CSF, G-CSF, MCP-1, and MIP-1ß), using a multiplex bead-based assay in 21 cases of rhinovirus- and 12 cases of RS virus-induced acute exacerbation of childhood asthma and 13 controls. We also compared the clinical data and the effects of systemic corticosteroids on these responses between rhinovirus and RS virus groups. RESULTS: The serum levels of ECP, IL-5, and IL-6 were significantly elevated in patients with rhinovirus-induced acute exacerbation of asthma compared with controls, while serum IL-1ß and IFN-γ were significantly lower in patients with rhinovirus-induced acute exacerbation of asthma than in controls. On the other hand, in RS virus-induced acute exacerbation of asthma, only the peripheral eosinophil count was significantly decreased compared with that in rhinovirus-induced acute exacerbation of asthma and controls. Furthermore, the serum levels of ECP, IL-5, and IL-6 in rhinovirus-induced acute exacerbation of asthma and levels of G-CSF in RS virus-induced acute exacerbation of asthma were significantly reduced after treatments that included systemic corticosteroids, respectively. CONCLUSION: These results suggest that the effects of systemic corticosteroids on serum ECP and the cytokine profile are different between rhinovirus- and RS virus-induced acute exacerbation of childhood asthma.

Different cytokine profile and eosinophil activation are involved in rhinovirus- and RS virus-induced acute exacerbation of childhood wheezing.

Because little information is available on eosinophil activation and cytokine response in virus-induced wheezing, we attempted to detect respiratory viruses and measure eosinophil cationic protein (ECP), and 27 types of cytokines/chemokines in both serum and nasal secretions from children with wheezing. This study was an observational, case-control investigation of 267 subjects, who were visited and/or hospitalized with acute respiratory symptoms (with wheezing: men, 115; women, 59; mean/median age, 3.6/3.0 years) or who were visited for regular physical examination and treatment (non-symptomatic wheezing: men, 48; women, 31; mean/median, 5.0/4.7 years), and 14 control subjects (controls: men, 9; women, 5; mean/median, 3.6/3.7 years). We detected viruses in nasal secretions from 174 patients with acute exacerbations of wheezing using antigen detection kits or reverse transcription-polymerase chain reaction, followed by direct DNA sequencing analysis. We measured peripheral eosinophil counts, and serum concentrations of ECP and 27 cytokines/chemokines using a multiplex bead-based assay in patients with wheezing or non-symptomatic wheezing. We also examined nasal ECP and 27 cytokines/chemokines in patients with wheezing. Of 174 samples from wheezing exacerbations, rhinovirus was detected in 59; respiratory syncytial (RS) virus in 44; enterovirus in 17; other viruses in 19; and no viruses in 35. Serum concentrations of ECP, IL-5, IL-6, IL-1ra, and IP-10 were significantly elevated in rhinovirus-induced wheezing compared with non-symptomatic wheezing. Similarly, serum ECP, IL-5, and IP-10 were significantly higher in rhinovirus-induced wheezing than in controls. On the other hand, IL-1ra and IP-10, but not ECP and IL-5 were significantly higher in RS virus-induced wheezing than in controls. Furthermore, only IL-5 was significantly elevated in the rhinovirus group compared with the RS virus group in both serum and nasal secretions. Different cytokine profile and eosinophil activation might be involved in rhinovirus- and RS virus-induced acute exacerbation of childhood wheezing.

Clinical features of 35 Down syndrome patients with transient abnormal myelopoiesis at a single institution.

Transient abnormal myelopoiesis (TAM) is a unique clonal myeloproliferation characterized by immature megakaryoblasts that occurs in 5-10% of neonates with Down syndrome (DS). Although TAM regresses spontaneously in most patients, approximately 20% of TAM cases result in early death, and approximately 20% of survivors develop acute megakaryoblastic leukemia (AMKL). We retrospectively reviewed records of 35 DS patients with TAM to determine the correlation between clinical characteristics and blast percentage. Thirteen of the 35 patients were classified as low blast percentage TAM (LBP-TAM), defined as TAM with a peak peripheral blast percentage ≤ 10%. Although no patient with LBP-TAM experienced systemic edema, disseminated intravascular coagulation, or early death, eight patients had elevated direct bilirubin levels (> 2 mg/dl) and one developed AMKL. All patients with LBP-TAM had serum markers of liver fibrosis that exceeded the normal limits, and two patients underwent liver biopsy to clarify the etiology of pathological jaundice. Taken together, our results suggest that patients with LBP-TAM may be at risk of liver fibrosis and liver failure, similarly to patients with classical TAM. Although these patients generally have a good prognosis, they should be carefully monitored for potential development of liver disease and leukemia.

Usefulness of virtual touch tissue quantification for predicting the presence of esophageal varices in patients with liver cirrhosis.

BACKGROUND AND AIM: Measuring the hepatic venous pressure gradient (HVPG) is an established technique to detect increased portal pressure and predict the presence of esophageal varices (EVs); however, the risk of the test is greater than the information it provides. This study aimed to clarify the usefulness of virtual touch tissue quantification (VTQ), which assesses liver stiffness, in predicting the presence of EVs in patients with liver cirrhosis by comparing it with HVPG. METHODS: Two hundred seventeen patients with liver cirrhosis underwent VTQ, HVPG measurement, and upper endoscopy. Patients were divided into three groups: group V, hepatitis C virus liver cirrhosis (n = 40); group A, alcoholic liver cirrhosis (n = 116); and group N, other liver cirrhosis (n = 61). In each group, we performed linear regression analysis of VTQ and HVPG data. The accuracy of VTQ and HVPG measurement in predicting the presence of EVs and high-risk EVs (EV category F2 and F3) was assessed by area under the receiver operating characteristic curve (AUROC). RESULTS: VTQ was significantly correlated with the HVPG in the whole patients and in each group, and both VTQ and HVPG values were significantly higher in patients with EVs and high-risk EVs than in those without. The AUROC for the presence of EVs for VTQ was 0.76 in the whole sample, 0.76 in group V, 0.79 in group A, and 0.67 in group N; and for HVPG, 0.92, 0.94, 0.93, and 0.88, respectively. For VTQ, the AUROC for the presence of high-risk EVs was 0.78 in the whole sample, 0.78 in group V, 0.73 in group A, and 0.73 in group N; and for HVPG, it was 0.85, 0.82, 0.85, and 0.82, respectively. CONCLUSION: VTQ was reliable at predicting the presence of EVs and high-risk EVs. Therefore, we propose that VTQ is a useful, noninvasive tool for predicting the presence of EVs in daily medical care.

Serum eosinophil cationic protein and 27 cytokines/chemokines in acute exacerbation of childhood asthma.

BACKGROUND: Little information is available on eosinophil activation and cytokine/chemokine responses in childhood asthma, thus we examined serum eosinophil cationic protein (ECP) and 27 types of cytokines/chemokines in acute exacerbation of asthma (acute asthma) and stable asthma. METHODS: We determined peripheral eosinophil count, and the serum levels of ECP and 27 types of cytokines/chemokines (IL-1 beta, IL-1 ra, IL-2, -4, -5, -6, -7, -8, -9, -10, -12, -13, -15 and -17, IFN-gamma, IP-10, TNF-alpha, GM-CSF, G-CSF, MCP-1, MIP-1 alpha and -1 beta, eotaxin, RANTES, PDGF-bb, FGF basic and VEGF) using a multiplex bead-based assay in 85 acute and 79 stable asthma patients, and 14 controls. We also examined the effects of systemic corticosteroids on these responses in acute asthma. RESULTS: The serum levels of ECP, IL-5, -6, -8 and -10, G-CSF, MCP-1, IL-1 ra and IP-10 were significantly elevated in acute compared with stable asthma. Similarly, serum levels of ECP, IL-5 and IP-10 were significantly higher in acute asthma than in controls. Furthermore, in the acute phase, elevated serum levels of ECP, IL-5, IL-6, IL-1 ra and IP-10, but not IL-8, IL-10, G-CSF and MCP-1 were significantly reduced after treatments that included systemic corticosteroids. CONCLUSION: Eosinophil activation could be induced by acute exacerbation of childhood asthma.

Prevalence and Risk Factor for Antibiotic-resistant Escherichia coli Colonization at Birth in Premature Infants: A Prospective Cohort Study.

BACKGROUND: Escherichia coli causes neonatal early-onset sepsis (EOS) that is associated with high mortality and increasing antibiotic resistance. Thus, we estimated the prevalence, antibiotic susceptibility and risk factors for colonization of E. coli in premature infants at birth and characterized the pathogenicity of the isolates. METHODS: A prospective surveillance study was conducted at three Japanese perinatal centers between August 2014 and February 2017. Infants weighing <2 kg and/or at gestational age <35 weeks at birth were enrolled. We screened the mothers and neonates for E. coli colonization. Pulsed-field gel electrophoresis was used to analyze the relatedness between the maternal and neonatal isolates. Virulence factors for the isolates were determined using polymerase chain reaction. RESULTS: We enrolled 421 premature infants born to 382 mothers. The rate of colonization in mothers was 47.6%, comprising 5.9% extended-spectrum beta-lactamase-producing E. coli (ESBL-E) and 20.0% ampicillin-resistant strains. Ten (2.4%) infants exhibited colonization; ESBL-E and ampicillin-resistant strains colonized three and four infants, respectively. Three antibiotic-resistant, strain-positive infants developed EOS. Pulsed-field gel electrophoresis revealed vertical transmission of bacteria in four infants. Multivariate logistic regression analysis revealed that ESBL-E-positive mothers [odds ratio (OR), 19.2; 95% confidence interval (CI), 2.5-145.7)] and vaginal delivery (OR, 9.4; 95% CI, 1.7-50.7) were risk factors for neonatal colonization. The infant isolates possessed numerous virulence factors. CONCLUSIONS: Although the prevalence of E. coli-colonized premature infants at birth was low, the rate of antibiotic resistance and the attack rate for EOS were high. Infants with ESBL-E positive mothers should be closely monitored for EOS.

Flux Growth and Magnetic Properties of Helimagnetic Hexagonal Ferrite Ba(Fe1-x Sc x )12O19 Single Crystals.

Fabricating large, high-crystalline-quality single-crystal samples of hexagonal ferrite Ba(Fe1-x Sc x )12O19 is the first important step to elucidating its helimagnetic structure and developing it for further applications. In this study, single crystals of Ba(Fe1-x Sc x )12O19 of various Sc concentrations x were successfully grown by the spontaneous crystallization method using Na2O-Fe2O3 flux. We determined the optimal starting composition of reagents for Ba(Fe1-x Sc x )12O19 growth as a function of x. In situ monitoring of the crystal nucleus generation accelerated the success of crystal growth. The obtained crystals comprised black and lamellate structures with a size of 13 mm × 8 mm × 2 mm and a surface of {001} orientation. X-ray diffraction and elemental analysis revealed that the obtained crystals were composed of single-phase Ba(Fe1-x Sc x )12O19 of high crystalline quality. The lattice constants a and c increased linearly with increasing x, thereby following Vegard's law. The temperature dependence of magnetization and the magnetization curves at 77 K of the x = 0.128 crystal exhibited behavior characteristics of helimagnetism. Neutron diffraction measurements of the x = 0.128 crystal exhibited magnetic satellite reflection peaks below 211 K, providing evidence that Ba(Fe1-x Sc x )12O19 behaves as a helimagnetic material.

SRD5B1 gene analysis needed for the accurate diagnosis of primary 3-oxo-Delta4-steroid 5beta-reductase deficiency.

BACKGROUND AND AIM: We encounter hyper-3-oxo-Delta(4) 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-Delta(4) bile aciduria from primary 3-oxo-Delta(4)-steroid 5beta-reductase deficiency. METHODS: To determine whether 3-oxo-Delta(4)-steroid 5beta-reductase (SRD5B1) gene analysis is required for the accurate diagnosis of 3-oxo-Delta(4)-steroid 5beta-reductase deficiency, we evaluated the laboratory data, bile acid analysis and SRD5B1 gene analysis from six patients with hyper-3-oxo-Delta(4) bile aciduria. RESULTS: Based upon the results, four patients who had developed neonatal liver failure were diagnosed as having neonatal hemochromatosis. Two patients with chronic cholestasis were diagnosed as having primary 3-oxo-Delta(4)-steroid 5beta-reductase deficiency by SRD5B1 gene analysis. The SRD5B1 gene in these two patients had a heterozygous mutation, G737A (Gly 223 Glu) in one patient and C217T (Arg 50 stop) in the other. CONCLUSIONS: Based upon our limited data, we conclude that SDR5B1 gene analysis is required for the accurate diagnosis of 3-oxo-Delta(4)-steroid 5beta-reductase deficiency. Moreover, we think that it is important to elucidate whether there is a heterozygous or a compound heterozygous mutation of the SRD5B1 gene in our two patients.

Flash Imaging Used in the Post-vascular Phase of Contrast-Enhanced Ultrasonography is Useful for Assessing the Progression in Patients with Hepatitis C Virus-Related Liver Disease.

Sonazoid is a commonly used contrast agent for characterizing liver tumors in ultrasonography (US). We performed flash imaging in the post-vascular phase of contrast-enhanced US (CEUS) to investigate associations between collapse of Sonazoid microbubbles (MB) and progression of liver disease. This study enrolled 409 patients (205 men, 204 women) with hepatitis C virus-related liver disease (CLD) between 2007 and 2017 (mean age 60 ± 14 y; range 20-90 y). In the post-vascular phase, 10 min after administering Sonazoid, flash imaging was performed to burst MB in the liver parenchyma; the range of bubble destruction was measured from the surface of the liver. The range of bubble destruction, stage of fibrosis, shear wave velocity (Vs), serologic markers and fibrosis-4 (FIB4) index were analyzed in 259 patients who underwent liver biopsy. Fibrosis stage was F0-1 in 108 patients, F2 in 73, F3 in 38 and F4 in 40. In 150 patients with cirrhosis, diagnosis was made based on imaging findings. The range of bubble destruction was 42.0 ± 10.4 mm in F0-1 patients, 42.9 ± 13.2 mm in F2, 51.5 ± 15.9 mm in F3 and 55.4 ± 17.3 mm in F4 and was significantly increased according to progression of fibrosis staging. The range of bubble destruction was positively correlated with Vs (r = 0.34; p < 0.01), total bilirubin (r = 0.25; p < 0.01) and FIB4 index (r = 0.38; p < 0.01). In contrast, the range of bubble destruction was negatively correlated with serum levels of albumin (r = -0.34; p < 0.01), platelet count (r = -0.35; p < 0.01) and prothrombin time (r = -0.36; p < 0.01). The results indicated that flash imaging in the post-vascular phase of CEUS was a non-invasive assessment and could predict disease progression in patients with CLD.