Ken Hisata

Dissemination of Methicillin-Resistant Staphylococci among Healthy Japanese Children

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA), regarded as a tenacious pathogen in the hospital, has recently become increasingly prevalent as a community pathogen. We evaluated the prevalence and characteristics of methicillin-resistant staphylococci in the Japanese community by testing nasal samples of 818 children of five day care centers and two kindergartens in three districts. We found that methicillin-resistant staphylococci are already prevalent among healthy children. Among 818 children, 35 children (4.3%) carried MRSA and 231 children (28.2%) carried methicillin-resistant coagulase-negative staphylococci (MRC-NS). The types of staphylococcal cassette chromosome mec (SCCmec) found among 44 MRSA isolates were as follows: type IIa, 11 isolates; type IIb, 19 isolates; and type IV, 14 isolates. The type IIb SCCmec element was a new SCCmec element found in this study. Eleven (25%) strains which belonged to clonal complex 5 (CC5) carried type IIa SCCmec, and they produced type 2 coagulase and toxic shock syndrome toxin 1. They were indistinguishable from health care-associated MRSA (H-MRSA) strains in Japan, represented by strain N315. On the other hand, 33 (75%) strains, most of which belonged to CC78 or CC91, carried small SCCmec elements, such as type IIb or type IV, and they produced type 1 or type 3 coagulase and exfoliative toxin. The data indicated that MRSA clones distinct from H-MRSA have disseminated in healthy children. The fact that MRC-NS strains were prevalent in the community suggested that they might serve as a reservoir for the SCCmec element carried by MRSA strains disseminated in the community.

Extreme Genetic Diversity of Methicillin-Resistant Staphylococcus epidermidis Strains Disseminated among Healthy Japanese Children

ABSTRACT For the past few years, we have been observing the dissemination of methicillin-resistant staphylococci in the community. From 2001 to 2003, an evaluation of nasal samples from 1,285 children in five day-care centers and two kindergartens in three districts in Japan revealed that methicillin-resistant coagulase-negative staphylococci (MRC-NS) have been widely disseminated in the Japanese community. Their prevalence is much greater than community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Forty-nine children (3.81%) were colonized with MRSA, whereas 390 children (30.35%) were colonized with MRC-NS. These MRC-NS strains predominantly harbored a pair of cassette chromosome recombinase types A2 and B2 (ccrAB2). Of these, 40.8% harbored type IVa staphylococcal cassette chromosome mec (SCCmec) elements, a distinct/characteristic type of SCCmec in pandemic clones of CA-MRSA. Interestingly, there was also a high frequency of nontypeable strains which possessed atypical structures compared to previous SCCmec types. Among the MRC-NS, the majority of strains (63.59%) were methicillin-resistant Staphylococcus epidermidis (MRSE). Their genotypes, as judged from pulsed-field gel electrophoresis (PFGE), were highly diverse. They were so diverse that there was no sign of an immediate transmission of any MRSE clone among children in the same institutions. In a previous report, we expounded that a few CA-MRSA clones with distinct SCCmec types were disseminated among children in the same institutions. Au contraire, with the case of CA-MRSE, there was no single genotype of CA-MRSE disseminated among children even in the same institution or class.

The pilot study: Sphingomyelin-fortified milk has a positive association with the neurobehavioural development of very low birth weight infants during infancy, randomized control trial

AIM This study was a randomised control trial to examine the effects of sphingomyelin (SM), on the mental, motor and behavioural development of premature infants. PATIENTS AND METHODS Randomised, double-blind controlled trial, enroling infants born with a birth weight of less than 1500 g between January 2004 and October 2007 at Juntendo University Hospital, with follow-up to 18 months. Twenty-four preterm babies were randomly assigned; 12 were assigned to a test group and fed SM-fortified milk (SM 20% of all phospholipids in milk) and 12 were assigned to a control group (SM 13% of all phospholipids in milk). We analysed the composition of the plasma phospholipids and red-cell-membrane fatty acids, after which VEP, Fagan, BSID-II, attention and memory tests were performed. RESULTS The percentage of SM in the total phospholipids was significantly higher in the trial group than in the control group at 4, 6 and 8 weeks. The Behaviour Rating Scale of the BSID-II, the Fagan test scores, the latency of VEP, and sustained attention test scores at 18 months were all significantly better in the trial group than in the control group. CONCLUSION This study is the first to report that nutritional intervention via administration of SM-fortified milk has a positive association with the neurobehavioural development of low-birth-weight infants. However, detailed studies on the effects of SM on longer-term development are required.

IGF-I, leptin and active ghrelin levels in very low birth weight infants during the first 8 weeks of life

Aim:  We investigated the relationship between plasma insulin‐like growth factor I (IGF‐I), leptin, active ghrelin levels, and postnatal growth in very low birth weight (VLBW) infants.

Efficacy of bacterial ribosomal RNA-targeted reverse transcription-quantitative PCR for detecting neonatal sepsis: a case control study

BackgroundNeonatal sepsis is difficult to diagnose and pathogens cannot be detected from blood cultures in many cases. Development of a rapid and accurate method for detecting pathogens is thus essential. The main purpose of this study was to identify etiological agents in clinically diagnosed neonatal sepsis using bacterial ribosomal RNA-targeted reverse transcription-quantitative PCR (BrRNA-RT-qPCR) and to conduct comparisons with the results of conventional blood culture. Since BrRNA-RT-qPCR targets bacterial ribosomal RNA, detection rates using this approach may exceed those using conventional PCR.MethodsSubjects comprised 36 patients with 39 episodes of suspected neonatal sepsis who underwent BrRNA-RT-qPCR and conventional blood culture to diagnose sepsis. Blood samples were collected aseptically for BrRNA-RT-qPCR and blood culture at the time of initial sepsis evaluation by arterial puncture. BrRNA-RT-qPCR and blood culture were undertaken using identical blood samples, and BrRNA-RT-qPCR was performed using 12 primer sets.ResultsPositive rate was significantly higher for BrRNA-RT-qPCR (15/39, 38.5%) than for blood culture (6/39, 15.4%; p = 0.0039). BrRNA-RT-qPCR was able to identify all pathogens detected by blood culture. Furthermore, this method detected pathogens from neonates with clinical sepsis in whom pathogens was not detected by culture methods.ConclusionsThis RT-PCR technique is useful for sensitive detection of pathogens causing neonatal sepsis, even in cases with negative results by blood culture.

Plasma levels of active ghrelin until 8 weeks after birth in preterm infants: relationship with anthropometric and biochemical measures

This study investigated the relationship between plasma levels of ghrelin and postnatal growth in preterm infants. The levels of active ghrelin in cord blood and in plasma in 25 very low birthweight (VLBW) infants were measured. The results indicate that the levels of circulating active ghrelin markedly increases after birth in VLBW infants, and suggest that the increased levels of ghrelin reflects the maturation of ghrelin production in the stomach and an increased physiological need for ghrelin.

Subtelomeric deletions of 1q43q44 and severe brain impairment associated with delayed myelination

Subtelomeric deletions of 1q44 cause mental retardation, developmental delay and brain anomalies, including abnormalities of the corpus callosum (ACC) and microcephaly in most patients. We report the cases of six patients with 1q44 deletions; two patients with interstitial deletions of 1q44; and four patients with terminal deletions of 1q. One of the patients showed an unbalanced translocation between chromosome 5. All the deletion regions overlapped with previously reported critical regions for ACC, microcephaly and seizures, indicating the recurrent nature of the core phenotypic features of 1q44 deletions. The four patients with terminal deletions of 1q exhibited severe volume loss in the brain as compared with patients who harbored interstitial deletions of 1q44. This indicated that telomeric regions have a role in severe volume loss of the brain. In addition, two patients with terminal deletions of 1q43, beyond the critical region for 1q44 deletion syndrome exhibited delayed myelination. As the deletion regions identified in these patients extended toward centromere, we conclude that the genes responsible for delayed myelination may be located in the neighboring region of 1q43.

Association between iron status and neurodevelopmental outcomes among VLBW infants

OBJECTIVE Our purpose was to evaluate iron status and neurodevelopmental outcomes in infants with and without extrauterine growth restriction (EUGR). METHODS This observational study evaluated 38 medically stable premature infants, with birth weights below 1500g. Iron status was determined by measuring venous levels of Hb, Fe, and serum ferritin. The infants were divided into EUGR and non-EUGR groups. At a corrected age of 18months, neurodevelopmental outcomes were checked using the Bayley scales, and body weight, body length, and head circumference were measured. RESULTS Hb levels at corrected ages of 1 and 3months and iron at a corrected age of 1 and 9months were significantly lower in the EUGR group compared with those of the non-EUGR group. There was no significant difference in the MDI score between the groups, but the PDI score at a corrected age of 18months was significantly lower in the EUGR group. We found a positive correlation between the serum level of Fe at 1month of age and PDI score at 18months of age. Head circumference at a corrected age of 18months did not differ between two groups, although body weight and length were lower in the EUGR group. CONCLUSIONS Developmental outcome in preterm infants at a corrected age of 18months may be influenced by nutritional factors, including iron status, during their early life.

Glucose metabolism soon after birth in very premature infants with small- and appropriate-for-gestational-age birth weights

UNLABELLED The intrauterine environment affects the development of insulin resistance in adulthood. To determine the influence of foetal growth restriction on glucose metabolism, we assessed indices of insulin sensitivity soon after birth in very premature infants. Blood samples were collected at birth from 52 premature infants with a gestational age of ≤31 weeks, who were divided into a group whose birth weight was small for their gestational age (SGA group, n=19) and a group whose birth weight was appropriate for their gestational age (AGA group, n=33). Blood glucose, serum insulin and C-peptide immunoreactivity (CPR) levels were measured in both groups. Furthermore, the quantitative insulin check index (QUICKI) was also calculated. Correlations between these indices and glucose metabolism and the standard deviation (SD) score for birth weight were also determined. The levels of insulin and CPR were significantly (p<0.05) lower in the SGA group than in the AGA group. The QUICKI was significantly (p<0.05) higher in the SGA group compared with the AGA group. The SD score for birth weight was correlated with the QUICKI (p<0.01), the serum insulin level (p<0.05) and the CPR level (p<0.05) in all 52 infants. CONCLUSION In very premature infants, poor foetal growth may impair foetal insulin secretion and affect the QUICKI at birth.

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.