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Kiyomi Matsuo,
Ichiro Morioka,
Mai Oda,
Yoko Kobayashi,
Yuji Nakamachi,
Seiji Kawano,
Miwako Nagasaka,
Tsubasa Koda,
Tomoyuki Yokota,
Satoru Morikawa, Akihiro Miwa,
Akio Shibata,
Toshio Minematsu,
Naoki Inoue,
Hideto Yamada,
Kazumoto Iijima
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ABSTRACT: BACKGROUND: Infants with congenital cytomegalovirus infection (CCMVI) may develop brain abnormalities such as ventricular dilatation, which may potentially associate with sensorineural hearing loss. There is currently no recognized method for quantitative evaluation of ventricle size in infants with CCMVI. Our objectives were to establish a method for quantitative evaluation of ventricle size using computed tomography (CT) in infants with CCMVI, and determine a cut-off value associated with abnormal auditory brainstem response (ABR) early in life. DESIGN/SUBJECTS: This study enrolled 19 infants with CCMVI and 21 non-infected newborn infants as a control group. Infants with CCMVI were divided into two subgroups according to ABR at the time of initial examination: normal ABR (11 infants) or abnormal ABR (8 infants). Ventricle size was assessed by calculating Evans' index (EI) and lateral ventricle width/hemispheric width (LVW/HW) ratio on brain CT images, and was compared among groups. A cut-off ventricle size associated with abnormal ABR was determined. RESULTS: EI and LVW/HW ratio were significantly higher in the CCMVI with abnormal ABR group than the control and CCMVI with normal ABR groups. Cut-off values of 0.26 for EI and 0.28 for LVW/HW ratio had a sensitivity of 100% and 100%, respectively, and a specificity of 73% and 91%, respectively, for association with abnormal ABR. CONCLUSIONS: We established a method for quantitative evaluation of ventricle size using EI and LVW/HW ratio on brain CT images in infants with CCMVI. LVW/HW ratio had a more association with abnormal ABR in the early postnatal period than EI.
Brain & development 01/2013; · 1.74 Impact Factor
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Tomoyuki Yokota,
Ichiro Morioka,
Takayuki Kodera,
Takeshi Morisawa,
Itsuko Sato,
Seiji Kawano,
Tsubasa Koda,
Kiyomi Matsuo,
Kazumichi Fujioka,
Satoru Morikawa, Akihiro Miwa,
Akio Shibata,
Naoki Yokoyama,
Masahiko Yonetani,
Hideto Yamada,
Hajime Nakamura,
Kazumoto Iijima
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ABSTRACT: BACKGROUND: Serum unbound bilirubin (UB) level measures bilirubin not bound to albumin, and has been reported to be better than total bilirubin level at identifying infants at risk of developing bilirubin-induced neurotoxicity, including auditory abnormalities. A detailed treatment strategy for newborns with high serum UB levels has not been established. Our objective was to assess auditory outcomes in newborns with serum UB levels of ≥1.00 μg/dL who were treated according to our novel treatment protocol. METHODS: A prospective clinical study was conducted in newborns weighing >1,500 g with serum UB levels of ≥1.00 μg/dL who were admitted to Kobe University Hospital and Kakogawa Municipal Hospital, Japan from 2006 to 2011. Enrolled newborns were treated as follows: (1) if the serum UB level was 1.00-1.50 μg/dL, phototherapy and infusion were administered with or without albumin or immunoglobulin therapy; and (2) if the serum UB level was >1.50 μg/dL, exchange transfusion was performed immediately. Auditory brainstem responses were evaluated at the time of discharge. RESULTS: A total of 89 Japanese newborns with UB levels of ≥1.00 μg/dL were enrolled at a median age of 4 days. Of these, 85 had UB levels of 1.00-1.50 μg/dL and four had UB levels of >1.50 μg/dL. After being treated according to our protocol, no newborns were diagnosed with auditory brainstem response abnormalities. CONCLUSIONS: Our treatment protocol for Japanese newborns with serum UB levels of ≥1.00 μg/dL may be useful for the prevention of bilirubin-induced auditory abnormalities.
Pediatrics International 09/2012; · 0.63 Impact Factor
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Ichiro Morioka,
Satoru Morikawa, Akihiro Miwa,
Hirotaka Minami,
Katsuhiko Yoshii,
Masaaki Kugo,
Yoshiki Kitsunezuka,
Miki Enomoto,
Takumi Jikimoto,
Masakuni Nakamura,
Naoki Yokoyama,
Hisahide Nishio,
Masafumi Matsuo,
Hideto Yamada
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ABSTRACT: Recent Japanese epidemiology of neonatal sepsis and its predominant pathogens has not been reported. It is also unknown whether there are center differences in the incidence of neonatal sepsis, including early-onset sepsis (EOS) and late-onset sepsis (LOS) in Japan.
To investigate the morbidity and characteristics of neonatal sepsis in recent years and the differences in the incidence of sepsis among Japanese neonatal care units.
We retrospectively collected the data of newborn infants with culture-proven sepsis that occurred in five Japanese centers of perinatal care from 2006 to 2008. The incidence of sepsis was calculated, including EOS and LOS, and compared among centers.
Morbidity from sepsis occurred in 51/6,894 (0.74%) infants. The incidence of EOS and LOS was 0.13 and 0.61%, respectively. The incidence of total sepsis and LOS in infants <1,000 g of birth weight was significantly higher than that in infants who weighed >1,000 g at birth, whereas there were no significant differences in the incidence of EOS between the different birth weights. Methicillin-resistant Staphylococcus aureus was the most common pathogen involved in morbidity and mortality of neonatal sepsis. Significant center differences were observed in the incidence of LOS, but not EOS.
The majority of culture-proven neonatal sepsis is LOS, which differs among centers, especially in infants who weigh <1,000 g at birth in Japan. We consider that it is important to control nosocomial infection in newborn care units to further reduce the morbidity of neonatal sepsis in Japan.
Neonatology 05/2012; 102(1):75-80. · 2.66 Impact Factor
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Akihiro Miwa,
Ichiro Morioka,
Tomoyuki Yokota,
Akio Shibata,
Kiyomi Matsuo,
Kazumichi Fujioka,
Tsubasa Koda,
Satoru Morikawa,
Hisahide Nishio,
Naoki Yokoyama,
Hajime Nakamura,
Masafumi Matsuo,
Hideto Yamada
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ABSTRACT: Free bilirubin concentration (B(f)) is an index for identifying newborns at risk for developing bilirubin-induced neurotoxicity. It has been suggested that B(f) measured by a single peroxidase concentration (B(f-single)) does not equal the equilibrium concentration of B(f), which is confirmed by B(f) at two different peroxidase concentrations (B(f-two)). However, the differences between B(f-single) and B(f-two) are unknown in the serum of term or late-preterm newborn infants. Furthermore, to apply B(f-single) with savings on time and cost to the clinical setting, it is very important for us to clarify the differences between B(f-single) and B(f-two).
Forty serum samples were obtained from 21 term or late-preterm newborns who were admitted at Kobe University Hospital. Using a peroxidase method, B(f-single) was measured at one peroxidase concentration, and B(f-two) was determined at two different peroxidase concentrations (the manufacturer's recommended peroxidase concentration and half the manufacturer's recommended peroxidase concentration). To clarify the relationship between B(f-single) and peroxidase concentrations, B(f-single) was measured at five different concentrations of peroxidase reagent. Intra-day and inter-day analyses were performed to assess the precision of B(f-single) and B(f-two).
1/B(f-single) increased as peroxidase concentration increased. B(f-single) was significantly lower than B(f-two) (B(f-single): 0.50 microg/dL [0.13 - 1.22 microg/dL] versus B(f-two): 0.59 microg/dL [0.15 - 1.76 microg/dL], p < 0.001), but B(f-single) was significantly correlated with B(f-two) (r = 0.953, p < 0.0001). Intra-day analysis showed that the CV was 9.7% for B(f-two) and 3.3% for B(f-single), and the inter-day CV was 12.4% for B(f-two) and 3.2% for B(f-single).
Although B(f-single) and B(f-two) are not identical, B(f-single) is significantly correlated with B(f-two) and it is more precise than B(f-two) in term or late-preterm newborns.
Clinical laboratory 01/2012; 58(5-6):507-14. · 0.90 Impact Factor
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Yumi Sato,
Ichiro Morioka, Akihiro Miwa,
Tomoyuki Yokota,
Kiyomi Matsuo,
Tsubasa Koda,
Kazumichi Fujioka,
Satoru Morikawa,
Akio Shibata,
Naoki Yokoyama,
Kaoru Takahashi,
Hisahide Nishio,
Masafumi Matsuo
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ABSTRACT: The American Academy of Pediatrics guidelines recommend that the total bilirubin (TB)/albumin (Alb) ratio (B/A ratio), instead of serum concentration of unbound bilirubin (UB), can be used with TB for determining treatment modality for jaundiced newborns ≥ 35 weeks of gestation. It is unknown, however, whether the B/A ratio is actually correlated with serum UB.
Four hundred and ninety-seven serum samples were obtained from 209 newborns ≥ 35 weeks of gestation, who were admitted to Kobe University Hospital. Serum UB concentration was measured using the glucose oxidase-peroxidase method. Serum TB and Alb concentrations were measured on spectrophotometry. B/A ratios were calculated and were linearly compared with serum UB. Furthermore, the accuracy of the B/A ratio was evaluated.
The B/A ratio was significantly correlated with serum UB concentration. A serum UB concentration of 0.6 µg/dL was in agreement with a B/A ratio of 0.5. For comparison of the number of newborns who had serum UB concentrations ≥ or <0.6 µg/dL and B/A ratios ≥ or <0.5, we found the following characteristics: the concordance rate between serum UB concentrations and the B/A ratio was 94%, sensitivity was 51%, and specificity was 99%.
The B/A ratio is significantly correlated with serum UB concentration in newborns ≥ 35 weeks of gestation. The B/A ratio, however, is underestimated when serum UB concentrations are >0.6 µg/dL.
Pediatrics International 08/2011; 54(1):81-5. · 0.63 Impact Factor
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Nature medicine 01/2011; 17(1):29-30; author reply 30-1. · 27.14 Impact Factor
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ABSTRACT: The serum concentration of unbound bilirubin (UB), which is bilirubin not bound to albumin (Alb), is a better index than total bilirubin concentration (TB) for identifying infants at risk for developing bilirubin neurotoxicity. The degree to which the hypoalbuminemia following abdominal surgery in jaundiced newborns affects bilirubin binding is unknown.
To determine whether lower Alb occurring in newborns undergoing abdominal surgery shortly after birth results in significantly higher UB in serum versus nonsurgical patients at comparable serum TB.
A matched case-control study was conducted with term and late-preterm newborns. The surgery group included 15 newborns who underwent abdominal operation within 3 days after birth. Clinical and laboratory data (serum UB, TB, and Alb concentrations, UB/TB ratio, and binding constant) in the surgery group were collected and compared with those of 30 control newborns who did not undergo abdominal surgery (control group).
Serum UB and the UB/TB ratio in the surgery group were significantly higher than those in the control group (p < 0.02, p < 0.001, respectively), whereas there were no significant differences in serum TB and binding constant between the groups. Serum Alb concentrations in the surgery group were significantly lower than those in the control group (p < 0.001). When pre- and postoperative serum Alb concentrations were compared, there was a significant decrease from 3.4 to 2.7 g/dl (p < 0.001).
Our study suggests that hypoalbuminemia following abdominal surgery causes a higher serum UB at comparable serum TB in newborns.
Neonatology 09/2010; 99(3):202-7. · 2.66 Impact Factor
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ABSTRACT: Autosomal dominant pseudohypoaldosteronism type 1 (PHA1) is a rare inherited condition that is characterized by renal resistance to aldosterone as well as salt wasting, hyperkalemia, and metabolic acidosis. Renal PHA1 is caused by mutations of the human mineralcorticoid receptor gene (MR), but it is a matter of debate whether MR mutations cause mineralcorticoid resistance via haploinsufficiency or dominant negative mechanism. It was previously reported that in a case with nonsense mutation the mutant mRNA was absent in lymphocytes because of nonsense mediated mRNA decay (NMD) and therefore postulated that haploinsufficiency alone can give rise to the PHA1 phenotype in patients with truncated mutations.
We conducted genomic DNA analysis and mRNA analysis for familial PHA1 patients extracted from lymphocytes and urinary sediments and could detect one novel splice site mutation which leads to exon skipping and frame shift result in premature termination at the transcript level. The mRNA analysis showed evidence of wild type and exon-skipped RT-PCR products.
mRNA analysis have been rarely conducted for PHA1 because kidney tissues are unavailable for this disease. However, we conducted RT-PCR analysis using mRNA extracted from urinary sediments. We could demonstrate that NMD does not fully function in kidney cells and that haploinsufficiency due to NMD with premature termination is not sufficient to give rise to the PHA1 phenotype at least in this mutation of our patient. Additional studies including mRNA analysis will be needed to identify the exact mechanism of the phenotype of PHA.
BMC Nephrology 11/2009; 10:37. · 2.18 Impact Factor
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Akio Shibata,
Ichiro Morioka,
Chitose Ashi,
Shizu Nagasaki,
Chisato Tode,
Satoru Morikawa, Akihiro Miwa,
Masahiro Enomoto,
Kayoko Saiki,
Naoki Yokoyama,
Atsuko Takeuchi,
Masafumi Matsuo
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ABSTRACT: N-acetyl Proline-Glycine-Proline (acPGP) is a novel neutrophil chemoattractant. However, no studies have been reported to identify the presence of acPGP in human serum. The purpose of our study was to establish a method for measuring acPGP, and to determine whether acPGP is present in human serum.
Serum samples were obtained from 22 healthy adults and 26 term and preterm newborns. For the sensitive analysis of acPGP, we utilized liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a multiple reaction monitoring (MRM) positive ion mode.
The major product ions of acPGP ([M+H](+) ion, m/z 312) appeared at 112 and 140. The MRM (transition: m/z 312/112) chromatogram in human serum showed a single peak with the same retention time as that of authentic acPGP. The calibration curve of authentic acPGP was linear, and our quantitative results indicated high precision. The mean serum acPGP levels in adults and newborns were 6.3 and 18.7 pg/ml, respectively. In newborns, lower birth weight infants had significantly higher serum acPGP levels.
We established a method for the quantification of serum acPGP using LC-MS/MS, and this paper provides the first evidence for the presence of acPGP in human serum of adults and newborns.
Clinica chimica acta; international journal of clinical chemistry 02/2009; 402(1-2):124-8. · 2.54 Impact Factor
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Akihiro Miwa
