Shinichi Niijima

Transient hyperoxia and cerebral blood flow velocity in infants born prematurely and at full term.

Little is known about the effects of hyperoxia on the cerebral circulation of human infants. Using duplex Doppler we measured the changes in cerebral blood flow velocity in a group of full term (n = 15) and premature infants (n = 17, median gestational age 31 weeks) in response to a transient threefold increase in oxygen tension. Measurements of blood gas tensions as well as blood pressure and cerebral blood flow velocity were made over a period of 20 minutes on three occasions for each infant; during normal oxygenation, hyperoxia, and normal oxygenation. There was a fall in cerebral blood flow velocity in 15 of the 17 premature infants with hyperoxia and the median reduction was 0.06 cm/second for every 1 kPa increase in oxygen tension. There was no significant change in either PCO2 or blood pressure during the period of hyperoxia. The cerebral blood flow velocity fell in all 15 infants born at full term during hyperoxia, but there was a simultaneous and significant reduction in PCO2 at the same time as the hyperoxia. Analysis of variance suggested that in the infants born at full term the change in carbon dioxide had most effect in the reduction of cerebral blood flow velocity, rather than the hyperoxia itself. We conclude that in premature infants, cerebral vascular resistance may be altered by a fall in cerebral blood flow velocity in the presence of hyperoxia.

Treatments with midazolam and lidocaine for status epilepticus in neonates

Status epilepticus (SE) occurs in children of all ages. Recent epidemiologic investigations of SE show heightened morbidity and mortality in newborns and young infants. However, the existing definition of SE in newborns is not precise and not easily applied in clinical investigations or in clinical practice. To evaluate the underlying conditions, clinical features and treatment of SE in neonates in Japan, a retrospective multi-center study was performed. In the initial investigation, questionnaires were sent to pediatric neurologists in 194 neonatal intensive care units of university hospitals, childrens hospitals, and general hospitals throughout in Japan. The questionnaires sought information on the background of each case, types of seizures, etiology of SE, treatments, results and adverse effects of treatment for patients less than 1 week old who had prolonged or frequently repeated seizures lasting more than 15 min and who are refractory to treatment with conventional anticonvulsants, such as diazepam (DZP), phenobarbital (PB) or phenytoin (PHT). As a secondary investigation, 65 cases from nine institutes, which completely fulfilled these criteria and were treated with midazolam (MDL) or lidocaine (Lid) to stop seizures were examined more fully. Subtle seizure and generalized tonic-clonic seizure were the most frequent seizure types. Neonatal SE was most frequently associated with hypoxic-ischemic encephalopathy, followed by intraventricular hemorrhage, central nervous system infections, and cerebral infarction. The final treatment outcome was available for 72.7% and 81.3% of MDL- and Lid-treated patients, respectively. Adverse effects of MDL and Lid were identified in 7.3% and 6.3% of patients, respectively. To reveal electroclinical seizures, clinical seizures without ictal discharge or other non-epileptic movements in neonates was important for appropriate treatment. MDL and Lid were useful drugs for the treatment of neonatal SE.

Carbamazepine-induced thrombocytopenia and leucopenia complicated by Henoch-Schönlein purpura symptoms

A rare case of carbamazepine-induced leucopenia and thrombocytopenia complicated by Henoch-Schönlein purpura (HSP) symptoms is presented. Laboratory findings suggested that leucopenia and thrombocytopenia could be due to bone marrow suppression and HSP symptoms to an allergic reaction to carbamazepine. To the best of our knowledge this is the first report that carbamazepine may cause haematological disorders associated with symptoms of HSP by different mechanisms at the same time in the same patient.

Studies on the conjugating activity of bile acids in children

ABSTRACT: The unconjugated and conjugated bile acid levels in sera of 98 normal children and nine normal adults were measured by high performance liquid chromatography. The results showed that the mean total bile acid level was high, 11.0 ± 8.7 μmol/liter (1 SD) during the neonatal period (0-4 wk) and then gradually decreased with age. The ratio of the concentration of conjugated bile acids to total bile acids in serum was as high as 90% or more in infants under 1 yr of age and slowly decreased with age. The mean ratio of cholic acid to chenodeoxycholic acid was high (1.7 ± 1.1) during the neonatal period but decreased after 3 months to the adult level (0.4 ± 0.2). The mean ratio of glycine conjugated bile acids to taurine conjugated bile acids was 3.0 ± 3.1 during the neonatal period and the ratio during the 1st month of life was significantly lower than that after that period with little further change at any age. The mean ratio of the concentration of secondary bile acids to primary bile acids showed significantly lower values in infants less than 1 yr of age. The main bile acid was glycocholic acid in the neonatal period but after 1-3 months glycochenodeoxycholic acid predominated. With age, the serum bile acid pattern which was characteristic in infancy gradually approached that of adults.

Parental Knowledge and Perceptions of Fever in Children and Fever Management Practices : Differences Between Parents of Children With and Without a History of Febrile Seizures

Objectives: The aim of this study was to compare maternal knowledge and perceptions of fever, fever management practices, and information sources of mothers of children with and without a history of febrile seizures. Methods: A questionnaire was used to survey mothers of children who visited health departments for a routine 18-month-old well baby check-up. Results: A total of 386 responses were analyzed. More mothers of children with a history of febrile seizures than mothers of children without it stated that high fever caused febrile seizures and antipyretics prevented it. Fewer mothers of children with a history of febrile seizures than mothers in the other group thought that high fever caused brain damage and antipyretics prevented the disease from worsening and warmed the childs body during fever episode. Many mothers in both groups stated that they considered physicians to be their primary information source. Spouse and own parents were named as information sources among mothers of children with a history of febrile seizures, whereas books and the Internet were named in the other group. Conclusions: Mothers of children with a history of febrile seizures demonstrated a higher rate of accuracy in their knowledge of fever than those in the other group. Mothers of children with a history of febrile seizures used personal communication, whereas those in the other group relied on mass communication for health information. Providing accurate information to family members is essential to provide mothers with both accurate information and emotional support.

Depressive tendency in children with growth hormone deficiency

Aim:  This study assessed changes in depressive tendency of children with growth hormone deficiency.

Sulfated and Nonsulfated Bile Acids in Urine of Patients with Biliary Atresia: Analysis of Bile Acids by High-Performance Liquid Chromatography

Summary To elucidate urinary bile acid patterns in patients with biliary atresia (BA), 15 sulfated and nonsulfated bile acids in urine were separately measured by high-performance liquid chromatography. This relatively simple technique for fluorescence detection utilizes the enzyme 3α-hydroxysteroid dehydrogenase (3α-HSD) to reveal urinary bile acid patterns. By this method, recovery rates of sulfated and nonsulfated bile acids in urine were satisfactory, and this analysis was shown to be applicable to clinical situations. In 10 patients with BA, the mean level of total bile acids in urine (23.35 ± 18.51 μmol/day) was seven times higher than the mean level in eight normal infants (3.05 ± 2.05 μmol/day). In the infants with BA, the mean level of total sulfated bile acids was about half of the total bile acid level. The main components of urinary nonsulfated bile acids in BA were glycocholic acid (6.21 ± 5.55 μmol/day) and taurocholic acid (2.28 ± 1.33 μmol/day), whereas the main components of the urinary sulfated bile acids were glycochenodeoxycholic acid (4.58 ± 6.97 μmol/day) and taurochenodeoxycholic acid (3.67 ± 3.54 μmol/day). Chenodeoxycholic acid, which is relatively toxic to the liver, may more easily be conjugated with sulfate and, hence, excreted into urine at a faster rate than cholic acid. Marked individual variations in urinary bile acid patterns were observed not only in BA patients but also in normal controls.

Does fever phobia cross borders? The case of Japan

Background:  Undue parental fear of fever in children was termed “fever phobia” by Schmitt following a survey in the USA in 1980. In 2000, Crocetti et al. conducted the same survey and concluded that fever phobia existed even 20 years later. In this study, we explore differences in fever phobia between these two US populations and a Japanese sample, and determine whether parents of a single child or those whose child was previously hospitalized or had a febrile seizure report greater anxiety about fever.

Autoimmune Focal Encephalitis Shows Marked Hypermetabolism on Positron Emission Tomography

A 22-month-old toddler presented with involuntary movements, hemiparesis, and behavioral changes. Magnetic resonance imaging showed no abnormality, but positron emission tomography (PET) showed focal hypermetabolism. By immunohistochemical technique with the patients sera in control brain sections, autoantibodies recognizing the same areas as found by PET scanning were identified and disappeared after intravenous immunoglobulin therapy. PET scanning may be useful in the diagnosis of autoimmune encephalitis.

HRAS mutants identified in Costello syndrome patients can induce cellular senescence: possible implications for the pathogenesis of Costello syndrome

Costello syndrome (CS) is a congenital disease that is characterized by a distinctive facial appearance, failure to thrive, mental retardation and cardiomyopathy. In 2005, we discovered that heterozygous germline mutations in HRAS caused CS. Several studies have shown that CS-associated HRAS mutations are clustered in codons 12 and 13, and mutations in other codons have also been identified. However, a comprehensive comparison of the substitutions identified in patients with CS has not been conducted. In the current study, we identified four mutations (p.G12S, p.G12A, p.G12C and p.G12D) in 21 patients and analyzed the associated clinical manifestations of CS in these individuals. To examine functional differences among the identified mutations, we characterized a total of nine HRAS mutants, including seven distinct substitutions in codons 12 and 13, p.K117R and p.A146T. The p.A146T mutant demonstrated the weakest Raf-binding activity, and the p.K117R and p.A146T mutants had weaker effects on downstream c-Jun N-terminal kinase signaling than did codon 12 or 13 mutants. We demonstrated that these mutant HRAS proteins induced senescence when overexpressed in human fibroblasts. Oncogene-induced senescence is a cellular reaction that controls cell proliferation in response to oncogenic mutation and it has been considered one of the tumor suppression mechanisms in vivo. Our findings suggest that the HRAS mutations identified in CS are sufficient to cause oncogene-induced senescence and that cellular senescence might therefore contribute to the pathogenesis of CS.