Osamu Otabe

Ring Chromosome 14 with Localization-related Epilepsy: Three Cases

Summary:  Three patients showing epileptic seizures and with mosaicism of ring chromosome 14 and monosomy for chromosome 14 are described. Patients were a 17‐year‐old boy, karyotype 46, XY, r(14)(p12q32.33)/45, XY, −14, a 7‐month‐old boy, karyotype 46, XY, r(14)(p11.2q32.33)/45, XY, −14, and a 10‐month‐old boy, karyotype 46, XY, r(14)(p12q32.31)/45, XY, −14. Microcephaly and alopecia were observed in the first patient. However, few dysmorphic features were found typical of ring 14 chromosome. He had exhibited complex partial seizures with secondary generalization at age 3 months and had mild motor and mental retardation. Both other patients had atonic seizures followed by staring, perioral cyanosis, and respiratory arrest at age 7 or 8 months. Both also showed mild developmental delay and had a few minor anomalies compatible with ring 14 chromosome. Interictal spikes were observed in the second patient in the right occipital region, whereas an interictal encephalogram of the third patient showed sporadic spikes in the left central region. In all three cases, seizures were resistant to common antiepileptic drugs.

The incidence and direct medical cost of hospitalization due to rotavirus gastroenteritis in Kyoto, Japan, as estimated from a retrospective hospital study

Anticipating imminent licensure of rotavirus vaccine for use in Japan, we estimated the incidence of rotavirus hospitalization and calculated the direct medical cost associated with rotavirus hospitalization in a hospital that provided virtually exclusive pediatric beds to the local community adjacent to the northern outskirts of metropolitan Kyoto, Japan. For a 2 year period between September, 2008 and August, 2010, there were 103 hospitalizations due to acute gastroenteritis among children less than 5 years of age. Stool specimens from 77 (75%) of the 103 hospitalized patients were tested for rotavirus antigen, and 46 (60%) were positive. The proportion of rotavirus positives was 65% in the peak-season months (January-June) and 17% in the off-season months (July-December). By extrapolating the test results to those patients with acute gastroenteritis who were not tested, 13 additional cases were estimated to be rotavirus positive. Assuming that all patients with rotavirus gastroenteritis less than 5 years of age in the catchment (5532 according to the 2005 census) were admitted to this hospital, the annual incidence of rotavirus hospitalization was estimated to be 4.1 (testing-unadjusted)-5.3 (adjusted) per 1000 child-years. Thus, it was estimated that one child in 48 or one child in 37 born in this area would be hospitalized due to rotavirus gastroenteritis by the age of 5 years. The incidence of rotavirus hospitalization was similar to the rate in Ise city (4.9 per 1000 child-years), also in central Japan, and lower than the rate in Honjo city in northern Japan (13 per 1000 child-years). Nevertheless, the burden of rotavirus hospitalization was substantial, and the total direct medical cost was estimated to be 6.6 billion Japanese Yen (US

Trastuzumab Activates Allogeneic or Autologous Antibody-Dependent Cellular Cytotoxicity against Malignant Rhabdoid Tumor Cells and Interleukin-2 Augments the Cytotoxicity

57 million). While economic analysis and comparisons with alternative preventive procedures may be necessary, this study provides the policymakers and pediatricians with further evidence that is necessary to decide whether to introduce rotavirus vaccines into the routine childhood immunization schedule in Japan.

Effect of a Single Inhalation of Laninamivir Octanoate in Children With Influenza

Purpose: Malignant rhabdoid tumor (MRT) is an early childhood cancer with poor prognosis. Trastuzumab, a humanized monoclonal antibody against human epidermal growth factor receptor-2 (HER-2), has been shown to be effective against breast cancer and other cancers. We investigated the effect of trastuzumab on MRT cell lines. Experimental Design: We examined expression of HER-2 on four MRT cell lines and two tumor tissues by indirect immunofluorescence, flow cytometry, and immunohistochemistry. The effect of trastuzumab against MRT cells was examined by cell growth assay. To observe the antibody-dependent cellular cytotoxicity of effector cells, we examined the cytotoxicity of trastuzumab in combination with allogeneic or autologous human peripheral blood mononuclear cells with and without IL-2 using the chromium release assay. Results: All four MRT cell lines and both MRT tissues expressed HER-2 protein. Trastuzumab alone did not reduce the viability of the MRT cell lines. On the other hand, the cytotoxicity of trastuzumab against each of the MRT cell lines was significantly increased by the presence of allogeneic and autologous peripheral blood mononuclear cells (P < 0.01). There was a strong correlation coefficient (r = 0.825) between HER-2 expression and the cytotoxicity enhanced by trastuzumab. Moreover, trastuzumab in combination with peripheral blood mononuclear cells augmented by interleukin-2 (IL-2) was significantly more cytotoxic than trastuzumab alone or IL-2 alone (P < 0.01). Conclusions: Our results indicate that (1) trastuzumab can exert antitumor effects on MRT cells by using the antibody-dependent cellular cytotoxicity of effector cells and (2) IL-2 can enhance the cytotoxicity of trastuzumab against MRT cells.

Incomplete Inhalation of Laninamivir Octanoate in Children with Influenza

OBJECTIVE: The purpose of this study was to compare the efficiency and safety of a new neuraminidase inhibitor, laninamivir octanoate (LO), with zanamivir (ZN) in pediatric patients with influenza. METHODS: One hundred twelve pediatric patients ≤15 years, diagnosed with a rapid diagnostic test as having influenza from January to May 2011, were randomly assigned to the LO group or the ZN group, and their parents were asked to complete a questionnaire during the recovery at home. The LO group was instructed to inhale LO once (20 or 40 mg depending on age), and the ZN group was instructed to inhale ZN (20 mg) twice daily for 5 days. RESULTS: The LO group (n = 55) and the ZN group (n = 57) were well balanced. Finally, 44 patients in the LO group and 41 patients in the ZN group could be evaluated. Median times to fever resolution after initial treatment were 36 hours in the LO group and 37 hours in the ZN group. No differences were observed between the 2 groups with respect to the frequencies of asthmatic symptoms, pneumonia, gastrointestinal symptoms, or abnormal behaviors. Six younger children could not inhale LO well for technical reasons. CONCLUSIONS: Our data suggest that the efficiency and safety of LO are the same as those of ZN in pediatric patients with influenza but that LO may be more convenient than ZN because it requires only a single inhalation. However, younger patients may not inhale LO efficiently.

Saffold cardiovirus infection in a 2-year-old boy with acute pancreatitis.

Background: Laninamivir octanoate (LO), an inhaled neuraminidase inhibitor, has been used against influenza in Japan. However, children who cannot inhale well might not receive the full dose. We examined the relation between the residual amounts of LO in the device after its use and the time to fever resolution in children with influenza. Methods: The subjects of the study were 161 children (4-15 years) who had been diagnosed as having influenza from 2011-2014 and who had demonstrated an ability to properly use an inhalation training device. After its use, the LO device was returned to the authors and the residual amount of LO was measured. After flu symptoms had resolved, the patients’ parents reported the time to fever resolution in a questionnaire. Results: The percentage of the residual LO was not significantly correlated with the time to fever resolution or with patient age. The percentage of residual LO tended to be higher and the time to fever resolution tended to be longer in 4-6 year-olds than in older children. In the 4-6 year group, seven patients were inhaling steroids. These patients tended to inhale more of the LO dose and tended to have a shorter time to fever resolution than the other patients. Conclusions: Physicians need to be aware that some 4-6 year-old influenza patients will not be able to inhale the full dose of LO. Influenza patients, even young ones, who are also inhaling steroids for other conditions are better able to inhale LO.

Effects of PAX3-FKHR on malignant phenotypes in alveolar rhabdomyosarcoma

Saffold cardiovirus (SAFV), first identified in a stool sample in 2007, is thought to be associated with respiratory disease and gastroenteritis. On the other hand, animal experiments suggested that the major viral load, following intraperitoneal inoculation of SAFV in mice, may be detected in the pancreas. However, until now, no cases of SAFV in patients with pancreatitis have been reported. This report presents a unique case in a patient who developed relapsing acute pancreatitis (AP) after hand, foot, and mouth disease, and was suspected to have SAFV-1 infection. A 2-year-old boy was admitted to the hospital because of severe abdominal pain. His serum amylase and lipase levels were elevated. Enhanced computed tomography showed pancreatic swelling and dilation of the main pancreatic duct, leading to a diagnosis of severe AP. The viral genome of SAFV-1 was detected by reverse transcription polymerase chain reaction from fecal samples. Furthermore, the serum neutralization titer for SAFV was elevated during AP, but decreased after 1 year. These findings strongly suggest the patient developed SAFV-1 infection concurrent with AP. Therefore, we propose that a cohort study is required to clarify the relationship between SAFV and AP.