Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 12 de 12
Filter
Add more filters










Publication year range
1.
Pediatr Int ; 65(1): e15581, 2023.
Article in English | MEDLINE | ID: mdl-37428855

ABSTRACT

BACKGROUND: Few studies have compared the efficacy and complications of dexmedetomidine (DEX) and fentanyl (FEN) in extremely preterm infants. METHODS: We conducted a single-institution, retrospective controlled before and after study of preterm infants before 28 weeks of gestation admitted between April 2010 and December 2018 to compare the complications and efficacy of DEX and FEN for preterm infants. Patients were administered FEN prior to 2015 and DEX after 2015 as the first-line sedative. A composite outcome of death during hospitalization and developmental quotient (DQ) < 70 at a corrected age of 3 years was compared as the primary outcome. Secondary outcomes including postmenstrual weeks at extubation, days of age when full enteral feeding was achieved and additional sedation by phenobarbital (PB) were compared. RESULTS: Sixty-six infants were enrolled into the study. The only perinatal factor that differed between the FEN (n = 33) and DEX (n = 33) groups was weeks of gestation. The composite outcome of death and DQ < 70 at a corrected age of 3 years were not significantly different. Postmenstrual weeks at extubation did not significantly differ between groups after adjustment for weeks of gestation and being small for gestational age. On the other hand, full feeding was significantly prolonged by DEX (p = 0.031). Additional sedation was less common in the DEX group (p = 0.044). CONCLUSION: The composite outcome of death and DQ < 70 at a corrected age of 3 years were not significantly different by DEX or FEN for primary sedation. Prospective randomized controlled trials should examine the long-term effects on development.


Subject(s)
Dexmedetomidine , Fentanyl , Infant , Infant, Newborn , Humans , Child, Preschool , Fentanyl/therapeutic use , Infant, Extremely Premature , Dexmedetomidine/therapeutic use , Retrospective Studies , Prospective Studies
2.
Congenit Anom (Kyoto) ; 62(5): 203-207, 2022 09.
Article in English | MEDLINE | ID: mdl-35751412

ABSTRACT

GATA4 is known to be a causative gene for congenital heart disease, but has also now been associated with disorders of sexual development (DSD). We here report a pathogenic variant of GATA4 in a 46,XY DSD patient with an atrial septal defect, identified by whole-exome sequencing to be c.487C>T (p.Pro163Ser). This mutation resulted in reduced transcriptional activity of the downstream gene. When we compared this transcriptional activity level with other GATA4 variants, those that had been identified in patients with cardiac defects and DSD showed less activity than those in patients with cardiac defect only. This suggests that the normal development of the heart requires more strict regulation of GATA4 transcription than testicular development. Further, when the different variants were co-expressed with wild-type, the transcriptional activities were consistently lower than would be expected from an additive effect, suggesting a dominant-negative impact of the variant via dimer formation of the GATA4 protein. Since these pathogenic GATA4 variants are occasionally identified in healthy parents, a threshold model of quantitative traits may explain the cardiac defect or DSD phenotypes that they cause.


Subject(s)
Disorder of Sex Development, 46,XY , Heart Defects, Congenital , Heart Septal Defects, Atrial , Disorder of Sex Development, 46,XY/diagnosis , Disorder of Sex Development, 46,XY/genetics , GATA4 Transcription Factor/genetics , GATA4 Transcription Factor/metabolism , Heart Defects, Congenital/diagnosis , Heart Defects, Congenital/genetics , Heart Septal Defects, Atrial/diagnosis , Heart Septal Defects, Atrial/genetics , Humans , Mutation
3.
Mol Ther Methods Clin Dev ; 20: 54-68, 2021 Mar 12.
Article in English | MEDLINE | ID: mdl-33376755

ABSTRACT

Various mitochondrial diseases, including mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), are associated with heteroplasmic mutations in mitochondrial DNA (mtDNA). Herein, we refined a previously generated G13513A mtDNA-targeted platinum transcription activator-like effector nuclease (G13513A-mpTALEN) to more efficiently manipulate mtDNA heteroplasmy in MELAS-induced pluripotent stem cells (iPSCs). Introduction of a nonconventional TALE array at position 6 in the mpTALEN monomer, which recognizes the sequence around the m.13513G>A position, improved the mpTALEN effect on the heteroplasmic shift. Furthermore, the reduced expression of the new Lv-mpTALEN(PKLB)/R-mpTALEN(PKR6C) pair by modifying codons in their expression vectors could suppress the reduction in the mtDNA copy number, which contributed to the rapid recovery of mtDNA in mpTALEN-applied iPSCs during subsequent culturing. Moreover, MELAS-iPSCs with a high proportion of G13513A mutant mtDNA showed unusual properties of spontaneous, embryoid body-mediated differentiation in vitro, which was relieved by decreasing the heteroplasmy level with G13513A-mpTALEN. Additionally, drug-inducible, myogenic differentiation 1 (MYOD)-transfected MELAS-iPSCs (MyoD-iPSCs) efficiently differentiated into myosin heavy chain-positive myocytes, with or without mutant mtDNA. Hence, heteroplasmic MyoD-iPSCs controlled by fine-tuned mpTALENs may contribute to a detailed analysis of the relationship between mutation load and cellular phenotypes in disease modeling.

4.
Eur J Med Genet ; 62(11): 103570, 2019 Nov.
Article in English | MEDLINE | ID: mdl-30414530

ABSTRACT

We report a patient with congenital complex pituitary hormone deficiency (CPHD) with intestinal malrotation and anal atresia. We identified a de novo heterozygous mutation, c.664T > G (p.Cys222Gly), in the FOXA2 gene in this individual. This missense mutation had the potential to affect the DNA binding properties of the FOXA2 protein based on a protein structure prediction. Since a CPHD patient with another missense mutation and one other case with an entire gene deletion have also been reported, we speculated that a haploinsufficiency of the FOXA2 gene might be a genetic etiology for this disorder. Phenotypic similarities and differences among these three cases are also discussed.


Subject(s)
Abnormalities, Multiple/genetics , DNA-Binding Proteins/genetics , Genetic Predisposition to Disease , Hepatocyte Nuclear Factor 3-beta/genetics , Hypothyroidism/genetics , Pituitary Hormones, Anterior/deficiency , Transcription Factor Pit-1/deficiency , Abnormalities, Multiple/physiopathology , Facies , Heterozygote , Humans , Hypothyroidism/physiopathology , Mutation, Missense/genetics , Pituitary Hormones, Anterior/genetics , Protein Conformation , Transcription Factor Pit-1/genetics
5.
Pediatr Cardiol ; 39(5): 902-905, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29532107

ABSTRACT

Reduced heart rate (HR) variability in preterm infants compared with full-term infants suggests that autonomic cardiac control is developmentally delayed. However, the association between developmental changes in myocardial repolarization and gestational age remains unknown. This study investigated the association between the myocardial repolarization lability index, namely the QT variability index (QTVI) = log10 [(QTv/QTm2)/(HRv/HRm2)], and the perinatal profile of healthy 1-month-old infants. We included 209 infants (143 boys and 87 girls; mean gestational weeks at birth, 38.6 ± 1.7) who were born in university hospitals between 2014 and 2015 without apparent cardiac disease. We compared the ECG variability indices in 28 infants born before 37 gestational weeks (mean gestational weeks at birth, 35.6 ± 1.1 as preterm) and 181 infants born at the average number of gestational weeks (mean gestational weeks at birth, 38.8 ± 1.1 as controls). There was a negative correlation between the QTVI and gestational weeks (r = - 0.460, p = 0.035). QTVI values in preterm infants were larger than those in the controls (0.01 ± 0.50 vs. -0.26 ± 0.48, p = 0.023). In conclusion, the QTVI is negatively correlated with gestational age. The QTVI can serve as an index of the maturity of the cardiac autonomic nervous system and myocardial depolarization.


Subject(s)
Autonomic Nervous System/physiology , Heart Rate/physiology , Infant, Premature/physiology , Case-Control Studies , Electrocardiography/methods , Female , Gestational Age , Humans , Infant , Infant, Newborn , Linear Models , Male , Predictive Value of Tests
6.
Cleft Palate Craniofac J ; 55(7): 1026-1029, 2018 08.
Article in English | MEDLINE | ID: mdl-28140668

ABSTRACT

Craniofrontonasal syndrome (CFNS) is a very rare genetic disorder, the common physical malformations of which include coronal synostosis, widely spaced eyes, clefting of the nasal tip, and various skeletal anomalies. Mutations of EFNB1, which encodes a member of the ephrin family of transmembrane ligands for Eph receptor tyrosine kinases, is the cause of CFNS. Although familial CFNS cases have been reported, no studies in the literature describe familial cases of CFNS expressing bilateral cleft lip and palate. Here, we describe a Japanese family with three cases of CFNS expressing bilateral cleft lip and palate.


Subject(s)
Cleft Lip/genetics , Cleft Palate/genetics , Craniofacial Abnormalities/genetics , Ephrin-B1/genetics , Female , Genetic Predisposition to Disease , Humans , Japan , Male
7.
J Infect Dis ; 217(4): 589-596, 2018 01 30.
Article in English | MEDLINE | ID: mdl-29165657

ABSTRACT

Background: This study was conducted to assess the transmissibility of rotavirus vaccine strains after rotavirus vaccination in a neonatal intensive care unit (NICU). Methods: Pentavalent (RV5) or monovalent (RV1) rotavirus vaccine was administered to infants admitted to the NICU. Nineteen vaccinated infants and 49 unvaccinated infants whose beds were located in close proximity to the vaccinated infants were enrolled in this study. Dissemination and fecal shedding of vaccine viruses within the NICU were examined using real-time reverse transcription-polymerase chain reaction. Results: Shedding of the vaccine strain was detected in all 19 vaccinated infants. RV5 virus shedding started 1 day after the first vaccination and persisted for 8 days after the first vaccination, and viral shedding terminated by day 5 after administration of the second RV5 dose. The kinetics of RV1 virus shedding differed among vaccinated infants. The duration of RV1 virus shedding was longer after the first vaccination than after the second vaccination. In contrast to the vaccinated infants, no vaccine virus genomes were detected in any of the stool samples collected from the 49 unvaccinated infants. Conclusions: This study is direct evidence of no transmission of rotavirus vaccine strains between vaccinated infants and unvaccinated infants in close proximity within a NICU.


Subject(s)
Feces/virology , Intensive Care Units, Neonatal , Rotavirus Vaccines/administration & dosage , Rotavirus/isolation & purification , Virus Shedding , Female , Humans , Infant , Infant, Newborn , Male , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Time Factors , Vaccines, Attenuated/administration & dosage
8.
Article in English | MEDLINE | ID: mdl-28211121

ABSTRACT

BACKGROUND: The QT variability index (QTVI) is a noninvasive index of repolarization lability that has been applied to subjects with cardiovascular disease. QTVI provides a ratio of normalized QT variability to normalized heart rate variability, and therefore includes an assessment of autonomic nervous activity. However, measurement of QT time is particularly difficult in children, who exhibit physiologically high heart rates compared with adults. In this study, we developed a set of standard values of J-point to Tpeak interval (JTp) for infants by age, and assessed the correlation of QTVI with the JTp variability index (JTpVI). METHODS: Subjects included 623 infants and children (0-7 years of age) without heart disease and 57 healthy university students. All subjects were divided into three groups by age. QTVI and JTpVI were calculated based on an electrocardiogram, and age-specific standard values, a gender-specific classification, and a standard growth curve were constructed. RESULTS: JTpVI markedly decreased in infancy and slowly decreased thereafter, reaching adult values by school age. There was also a strong correlation of JTpVI with QTVI (r = .856). CONCLUSIONS: JTp can be used to evaluate the variability of the repolarization time in healthy infants, and may be useful for detection of early repolarization abnormalities.


Subject(s)
Electrocardiography/methods , Electrocardiography/statistics & numerical data , Heart Rate/physiology , Adult , Age Factors , Child , Child, Preschool , Female , Humans , Infant , Male , Reproducibility of Results , Young Adult
9.
Pediatr Cardiol ; 38(3): 582-587, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28058479

ABSTRACT

Atrial septal defect is a common congenital heart disease. In patients with atrial septal defect, left-to-right shunting increases the right atrial and right ventricular preload. This pathological change affects sinus node automaticity and myocardial depolarization and repolarization, and has the potential to evoke arrhythmogenic substrates. We examined the effect of atrial septal defect on sinus node automaticity and myocardial repolarization by investigating the variability in the repolarization interval, namely the QT variability index (QTVI) and variability ratio (VR). This retrospective study included 38 patients (mean age, 2.2 ± 1.9 years; mean left-to-right shunt ratio, 2.1 ± 0.70) and 40 age-matched healthy control subjects evaluated from 2008 to 2015. QTVI was calculated using the ratio of the repolarization parameter variance to heart rate variance, and VR was calculated as the ratio of the standard deviation (SD) of QT intervals to the SD of RR intervals on electrocardiography. There was a significant difference in the SD of all normal RR intervals, heart rate variance, VR, and QTVI of control subjects or patients with low shunt ratio compared with patients with high shunt ratio (all P < 0.05). Linear regression analysis revealed strong positive correlations between the left-to-right shunt ratio and VR (r = 0.662, P < 0.0001) or QTVI (r = 0.808, P < 0.0001). These repolarization indices provide information on alteration of sinus node autonomic control and the pathophysiology of myocardial repolarization, and could be used as a noninvasive indicator of the shunt ratio in children with atrial septal defect.


Subject(s)
Arrhythmias, Cardiac/physiopathology , Autonomic Nervous System/physiopathology , Electrocardiography , Heart Septal Defects, Atrial/physiopathology , Case-Control Studies , Child, Preschool , Female , Heart Rate , Humans , Infant , Japan , Linear Models , Male , Retrospective Studies
10.
J Hum Genet ; 61(8): 701-3, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27053290

ABSTRACT

Hypertension and brachydactyly syndrome (HTNB) with short stature is an autosomal-dominant disorder. Mutations in the PDE3A gene located at 12p12.2-p11.2 were recently identified in HTNB families. We found a novel heterozygous missense mutation c.1336T>C in exon 4 of the PDE3A gene in a Japanese family with multiple HTNB patients. This mutation was found to be completely linked to the family members who inherited this condition. The mutation, resulting in p.Ser446Pro, was located within the cluster region of reported mutations. This mutation may also affect the phosphodiesterase activity of PDE3A to reduce the cyclic AMP level in the cell and thereby influencing the development of limbs and the function of the cardiovascular system.


Subject(s)
Brachydactyly/diagnosis , Brachydactyly/genetics , Cyclic Nucleotide Phosphodiesterases, Type 3/genetics , Hypertension/diagnosis , Hypertension/genetics , Mutation , Amino Acid Substitution , Child , DNA Mutational Analysis , Exome , Female , Genetic Association Studies , High-Throughput Nucleotide Sequencing , Humans , Male , Pedigree , Phenotype , Polymorphism, Single Nucleotide , Syndrome
11.
BMC Med Genet ; 16: 98, 2015 Oct 26.
Article in English | MEDLINE | ID: mdl-26502924

ABSTRACT

BACKGROUND: In the present study, we report on a couple who underwent prenatal genetic diagnosis for autosomal recessive polycystic kidney disease (ARPKD). CASE PRESENTATION: This healthy couple had previously had a healthy boy but had experienced two consecutive neonatal deaths due to respiratory distress resulting from pulmonary hypoplasia caused by oligohydramnios. The woman consulted our facility after she realized she was pregnant again. We promptly performed a carrier test for the PKHD1 gene by target exome sequencing of samples from the couple. A pathogenic mutation was identified only in the paternal allele (c.9008C>T, p.S3003F). The mutation was confirmed by Sanger sequencing of the DNA from formalin-fixed, paraffin-embedded, kidney tissue of the second neonate patient and was not found in the healthy sibling. We then performed haplotype analyses using microsatellite markers scattered throughout the PKHD1 gene. DNA from the amniocentesis was determined to belong to a carrier, and the couple decided to continue with the pregnancy, obtaining a healthy newborn. Subsequent detailed examination of the exome data suggested higher read depth at exons 45 and 46. Multiplex ligation-dependent probe amplification allowed identification of duplication of these two exons. This case suggests the potential usefulness of target exome sequencing in the prenatal diagnosis of the PKHD1 gene in ARPKD. CONCLUSIONS: This is the first report of intragenic duplication in the PKHD1 gene in ARPKD.


Subject(s)
Mutation , Polycystic Kidney, Autosomal Recessive/diagnosis , Polycystic Kidney, Autosomal Recessive/genetics , Receptors, Cell Surface/genetics , Amniocentesis/methods , Exome , Female , Humans , Male , Pregnancy , Sequence Analysis, DNA , Young Adult
12.
Pediatr Cardiol ; 35(7): 1268-72, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24823886

ABSTRACT

Kawasaki disease complicates with myocarditis and vasculitis. Even if myocarditis is asymptomatic, heterogeneity of ventricular repolarization may be increased in the acute phase. We evaluated whether the change in repolarization characteristics can be used as a predictor for myocarditis and coronary lesions. Enrolled 34 children who were treated with intravenous immunoglobulin therapy. There were no sequelae in the recovery phase in any subjects, including those who had transient coronary artery lesion. QT and the interval from the Tpeak to Tend (Tp-e) were determined. The Tp-e/QT ratios were compared between the acute and recovery phases and correlations with CRP level and body temperature were evaluated. A retrospective evaluation of Tp-e/QT as predictors of coronary dilation was also performed. Tp-e/QT in the acute phase correlated positively with body temperature and CRP level. In a comparison of patients with and without transient coronary artery lesion, Tp-e/QT was significantly higher in those with dilation. In conclusion, Tp-e/QT was strongly related to transient coronary dilation, in comparison with inflammatory indicators including fever and CRP level.


Subject(s)
Electrocardiography , Heart Conduction System/physiopathology , Inflammation/complications , Mucocutaneous Lymph Node Syndrome/complications , Tachycardia, Ventricular/etiology , Child, Preschool , Echocardiography , Female , Follow-Up Studies , Humans , Inflammation/diagnosis , Inflammation/physiopathology , Male , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/physiopathology , Retrospective Studies , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/physiopathology
SELECTION OF CITATIONS
SEARCH DETAIL
...