Incidence of childhood primary immune thrombocytopenic purpura.

There is a discrepancy in the reported incidence of childhood immune thrombocytopenic purpura (ITP) between Europe (2.9-5.3 per 100 000 persons) and Japan (1.91). Ise district is a suitable area in which to conduct epidemiological study because there is little fluctuation in the sociodemographic factors. We performed a retrospective population-based study to clarify the incidence of primary childhood ITP. We calculated person-years for children aged <15 years based on the Ise district demographics between 2002 and 2012. The calculated person-years were 298 533. The number of hospitalized patients in Ise district was 25 (M/F, 14/11) during the study period. The calculated incidence was therefore 8.4 per 100 000 person-years. It is possible that the difference in incidence between the present calculation and that of the European studies is due to variation in accuracy and/or registration criteria between the studies.

Edwardsiella tarda is an Important Causative Agent of Maternal-Fetal Infections in Pregnant Women: a Case Report and Japanese Literature Review.

Volume 76, no 1, p. 80-83, 2023. Page 81, Table 1 should appear as shown below.

Edwardsiella tarda is an Important Causative Agent of Maternal-Fetal Infections in Pregnant Women: a Case Report and Japanese Literature Review.

We present a case study of a 6-day-old male infant who was referred to our hospital for fever, jaundice, and poor suckling, and was diagnosed with meningitis due to Edwardsiella tarda. We were able to detect E. tarda DNA after performing broad-range polymerase chain reaction targeting the bacterial 16S rRNA gene followed by a Basic Local Alignment Search Tool analysis of the DNA extracted from the cerebrospinal fluid. Furthermore, Japanese literature review showed that E. tarda caused perinatal invasive infections in mothers and infants and that the risk of fetal meningitis might be related to the food preference of Japanese people for raw fish. It is crucial to disseminate the information that pregnant women should refrain from eating high-risk raw fish, including freshwater fish.

Combination of prednisolone and cyclosporine A as third-line therapy for refractory Kawasaki disease.

BACKGROUND: The selection of drugs as third-line therapy for patients with Kawasaki disease (KD) who are resistant to second-line therapy remains controversial. METHODS: We reviewed the medical records of 354 patients (216 males/137 females) with KD who were treated in our department from July 2003 to January 2016. The age range was 1 month to 10 years, and the median age was 2 years and 1 month. A combination of 2 g/kg intravenous immunoglobulin (IVIG) plus 30 mg/kg of aspirin was used as first-line therapy. Patients who were refractory to the first-line therapy were administered 2 mg/kg of prednisolone (PSL) in combination with IVIG. Five patients who were refractory to the second-line therapy were treated with cyclosporine A (CsA) combined with PSL as the third-line therapy. RESULTS: All five patients immediately responded to the third-line therapy. One of the five patients showed a transient dilatation of the coronary artery that regressed to its normal size by the 60th day of illness. CONCLUSIONS: We suggest that the combination of CsA and steroids might be a promising therapeutic strategy for refractory KD.

Acute motor-sensory axonal Guillain-Barré syndrome with unilateral facial nerve paralysis after rotavirus gastroenteritis in a 2-year-old boy.

Guillain-Barré syndrome (GBS) is well known as presenting with acute immune-mediated polyneuropathies, with strong associations with antecedent infections. Several variant forms of GBS have been described, including acute inflammatory demyelinating polyneuropathy, acute motor axonal neuropathy, acute motor-sensory axonal neuropathy, and sensory GBS. We present a rare case of 2-year-old boy with acute motor and sensory polyneuropathy and left-sided facial nerve paralysis after rotavirus infection. He received immunoglobulin i.v. with subsequent satisfactory recovery.

An 8-year-old boy with hypereosinophilic syndrome.

Hypereosinophilic syndrome (HES) is a heterogeneous group of uncommon disorders characterized by the presence of marked peripheral blood eosinophilia and tissue eosinophilia, resulting in a wide variety of clinical manifestations. We present the case of an 8-year-old boy with HES. He complained of recurrent abdominal pain, general fatigue, and diarrhea. Laboratory data showed marked eosinophilia, elevated total IgE with positive specific IgE antibodies to common inhalant and food allergens, and elevated serum CCL17/TARC. A chest CT scan revealed central bronchiectasis, bronchial wall thickening, a mosaic attenuation pattern, and multiple small nodules in lung parenchyma; abdominal CT showed a thickened bladder wall. Gastrointestinal endoscopy revealed scarring in the gastric mucosa and mucosal erosion in the duodenum. Immunohistochemical examination demonstrated numerous eosinophil infiltrations with extensive extracellular eosinophil major basic protein deposition in the gastric mucosa. Only high-dose oral steroid was effective and cyclosporine appeared to have a steroid-sparing effect. HES is extraordinary rare in children and the long-term prognosis in pediatric HES is not well known. Comprehensive diagnostic procedures are vital for the early detection and management of complications in pediatric HES.

Evaluation of Japanese practice guidelines for newly diagnosed childhood idiopathic thrombocytopenic purpura.

BACKGROUND: Practice guidelines for childhood idiopathic thrombocytopenic purpura (ITP) were proposed in 1998 and 2004 in Japan. It is important to evaluate the feasibility and validity of the guidelines because the guidelines are based not on evidence but on opinion. METHODS: Records of 30 consecutive hospitalized patients aged 0-15 years (median, 3 years; 17 boys, 13 girls) were retrospectively reviewed. The feasibility and validity of the 2004 guidelines were evaluated by calculating an implementation rate, a response rate to first treatments, and a final clinical outcome. RESULTS: Deviation from the guidelines was found in two patients. Management of the other 28 patients followed the guidelines. The implementation rate was 93.3%. Twenty-one of the 28 eligible patients (75%) responded to the first treatment, whereas seven patients (25%) required additional treatment. In 23 patients (76.7%) platelet counts returned to normal within 6 months. Seven patients (23.3%) developed chronic conditions. All patients had no complications and achieved a platelet count >150 000/µL within 6 years. CONCLUSION: The 2004 Japanese guidelines are feasible and valid for the management of newly diagnosed childhood ITP patients.

[Clinical investigation of nine pediatric Japanese spotted fever cases].

To clarify the clinical manifestations of pediatric Japanese spotted fever (JSF), which remain unclear, we retrospectively reviewed the records of 9 consecutive hospitalized children 5 boys and 4 girls aged 0-15 years (median: 2.3) whose diagnosis was patients with JSF who were serologically confirmed from April 2008 to October 2009. We initially studied the polymerase chain reaction (PCR) assay validity for specific Rickettsia japonica DNA in the blood. We also studied febrile duration, the history of contact with tick-infested areas, body temperature, eschars at tick bite sites, skin rash, treatment drugs, and laboratory data. Five of the 9 (56%) had positive PCR tests. Prehospitalization febrile duration was 1-5 days. Five had had contact with tick-infested areas and 4 had not despite living near such areas. Body temperature was 40 degrees C in 7. Only 4 had eschars at bite sites. Characteristic spotted palmar and/or plantar erythema seen in 8 was useful in diagnosis. Laboratory studies showed typical hyponatremia of < 135mEq/L in 6 JSF was diagnosed easily at hospitalization in 7. Diagnosis in a 2-month-old infant proved difficults, however, worsening the child's condition and causing hepatosplenomegaly, thrombocytopenia, anemia, and hyperferritinema. The infant was treated with high-dose gamma-globulin and azithromycin (AZM) followed by minocycline (MINO). Another case was difficult to diagnose due to clinical manifestations consistent with Kawasaki disease. The child was treated with high-dose gamma-globulin and AZM. Three of the 9 were treated with MINO alone and 4 with combined MINO and new quinolones. Fever was resolved within 2 days of treatment in all cases. Our findings show that children with high fever and spotted palmar and/or plantar erythema should be treated immediately for JSF in prevalent areas, even in the absence of eschars.

Effectiveness of self-financed rotavirus vaccination in Ise City, Japan.

In Japan, the herd immunity effect of rotavirus vaccine has not yet been proven. Here, we conducted active surveillance for hospitalization due to rotavirus acute gastroenteritis (AGE) among children under 5 years of age in pre-rotavirus vaccination years and self-financed rotavirus vaccination years to clarify the rotavirus vaccine effectiveness (VE) in reducing hospitalization rates. A time-series analysis showed that the monthly hospitalization rates observed after vaccine introduction were significantly lower than the forecasted hospitalization rates (p < .001, Mann-Whitney U test). In the third year after vaccine introduction, the hospitalization rate declined despite the low vaccination rate of 27-50% for the two preceding years. We estimated four types of VE, namely direct, indirect, total, and overall. The direct VE was calculated from the relative risk ratio of hospitalizations between vaccinated and unvaccinated children. The indirect VE was defined as the population-level effects of vaccination on children not receiving the vaccine. The total VE was defined as the combination of the direct and indirect VE on children receiving the vaccine. The overall VE was determined by the weighted average of indirect VE on the children not receiving the vaccine and the total VE on the children receiving the vaccine. The direct, indirect, total, and overall VE values were calculated as 82% (95% confidence interval, 52-93), 70% (51-82), 95% (87-98), and 86% (77-91), respectively. The high values of indirect, total, and overall VE indicate that the rotavirus vaccine produces a herd immunity effect.

Vaccine-associated paralytic poliomyelitis in an infant with perianal abscesses.

We describe a case of vaccine-associated paralytic poliomyelitis (VAPP) in a 7-month-old infant with perianal abscesses. The infant had suffered from perianal abscesses from 3 weeks after birth. The abscesses repeatedly developed and spontaneously drained through the orifice. Twenty-seven days before admission, a live attenuated oral poliovirus vaccine (OPV) was given to the infant for the first time for routine immunization. His body temperature rose to 38°C 19 days after receiving the OPV and fell 4 days later. Flaccid paralysis of the right leg appeared 26 days after receipt of the OPV. A Sabin type 3 poliovirus was isolated from a stool obtained at admission. The DNA sequences of the VP1 region of the isolated virus were more than 99% identical with those of the vaccine strain. Mild muscle atrophy with moderate motor impairment in the right leg persisted at 18 months of age. One VAPP case provoked by a perianal abscess has been reported from the United Kingdom. Database search revealed that one of nine VAPP cases reported during 2003-2008 in Japan had a perianal abscess. Taken together, these reports and our case imply that we should give OPV with caution to infants with a perianal abscess.

Prevalence of Mycoplasma IgM in children with lower respiratory tract illness.

BACKGROUND: Few data are available for the recent occurrence of Mycoplasma infections in children in Japan. The purpose of the present study was therefore to identify the prevalence of Mycoplasma infections in children in Japan. METHODS: IgM antibodies to M. pneumoniae were prospectively determined using the Meridian ImmunoCard Mycoplasma test in hospitalized patients with lower respiratory tract infections between January 2004 and June 2007. A total of 858 hospitalized patients aged 0-15 years (445 male, 413 female), diagnosed as having acute pneumonia or bronchitis, were enrolled. The number of patients with pneumonia or bronchitis was 331 (male/female, 167/164) and 527 (male/female/ 278/249), respectively. Two hundred and five of the 858 patients (23.9%) were ImmunoCard positive. Of the 205 patients, 121 children and 84 children were diagnosed as having pneumonia and bronchitis, respectively. One hundred and forty-three of the 727 patients (19.7%) <5 years of age were ImmunoCard test positive. CONCLUSIONS: M. pneumoniae infection is not rare in children aged <5 years in Japan.

Marginal decrease in mortality and marked increase in incidence as a result of neuroblastoma screening at 6 months of age: cohort study in seven prefectures in Japan.

PURPOSE: To determine the usefulness of 6-month screening for neuroblastoma. PATIENTS AND METHODS: The cumulative incidence rates (IRs) and cumulative mortality rates (MRs) of neuroblastoma in children younger than 60 months of age were analyzed for control (n = 713,025), qualitative screening (Qual Screen, n = 1,142,519), and quantitative screening (Quan Screen, n = 550,331) cohorts, and for Screened and Unscreened subgroups within screening cohorts. RESULTS: IRs (per 100,000) for infants aged 6 to 11 months were 1.12 in Control, 5.69 in Qual Screen (P <.0001), and 17.81 in Quan Screen (P <.0001); IRs for children aged 12 to 59 months were 7.29 in Control, 5.86 in Qual Screen (P =.28), and 6.36 in Quan Screen (P =.60). IRs for children aged 12 to 59 months in Unscreened or Screened subgroups remained at the same level. When patients diagnosed at younger than 6 months of age were excluded, the MR (per 100,000) under 60 months for Control was 4.21; those in Unscreened and Screened subgroups were 3.84 and 2.53 in Qual Screen (P =.30), and 3.20 and 1.97 in Quan Screen (P =.73), respectively; MRs between Control and Unscreened subgroups revealed no significant differences (P =.89 in Qual Screen, P =.85 in Quan Screen). CONCLUSION: Six-month screening resulted in a marked increase in incidence for infants with no significant decrease in incidence for children older than 1 year of age. A decrease in mortality was observed, but it was not significant. The usefulness of screening is questionable, because the decrease of mortality should be balanced against the adverse effect of overdiagnosis and the psychological burden on parents and children.

Role of Ca2+ in the intracellular signaling pathway of anti-IgM-induced apoptosis in the human B-cell line, MBC-1, established from Burkitt lymphoma.

The role of Ca2+ in the intracellular signal transduction process that causes antibody-induced apoptotic cell death in B-cells is not completely understood. We previously established a B-cell line (MBC-1) from a patient with Burkitt lymphoma at the leukemic stage that demonstrated the typical morphology and internucleosomal DNA fragmentation of apoptosis when treated with anti-immunoglobulin (Ig)M antibody. This antibody-induced cell death was partially inhibited by pretreatment with ethyleneglycol-bis-tetraacetic acid (EGTA) and actinomycin-D. FK506, an immunosupressive agent and calcineurin inhibitor, also partially rescued the anti-IgM antibody-induced death of MBC-1 cells. These results show that the calcium signaling pathway, which leads to a change in gene expression, plays an important role in anti-IgM-induced apoptosis in MBC-1 cells. Flow cytometric measurement of the cytosolic free Ca2+ concentration ([Ca2+]i) showed that nontoxic concentrations of 4-bromo-calcium ionophore A23187 (Ca2+ IP) increased [Ca2+]i more than did the anti-IgM antibody. A brief Ca2+ spike was observed on anti-IgM antibody treatment, but a gradual increase and decrease were observed when the cells were treated with Ca2+ IP at a nontoxic concentration of 1 microg/mL. These findings suggest that interpretations differ for the 2 patterns of calcium signaling and that the brief spiked elevation of Ca2+ produces distinct biological and cellular responses compared to the gradual increase and decrease of [Ca2+]i. Our results support the hypothesis that Ca2+ plays a significant role as a multifunctional second messenger providing specific information to the nucleus in anti-IgM antibody-induced apoptosis in MBC-1 cells.

Diamond-Blackfan anemia in Japan: clinical outcomes of prednisolone therapy and hematopoietic stem cell transplantation.

The epidemiology and treatment outcomes for Diamond-Blackfan anemia (DBA) were surveyed in a cohort of 54 children (M/F = 26:28) registered in Japan from 1988 to 1998. The annual incidence was 4.02 cases per million births, the median age at diagnosis was 60 days, and 59% of the cases presented by 3 months of age. Three patients had a familial occurrence. All patients received prednisolone (PSL), and cyclosporin A (CsA) was added to the therapy in 17 patients. Forty-seven patients received transfusions, and 13 underwent hematopoietic stem cell transplantation (HSCT). The cumulative probabilities of a medication-free or a transfusion-free state prior to HSCT were 36% and 69%, respectively, at more than 5 years after diagnosis. Thirteen patients were weaned from PSL therapy without HSCT, and CsA was not associated with weaning from therapy. Transfusion and medication were stopped at 249 days and 933 days after diagnosis in 34 and 13 patients, respectively, who achieved a state of independence. No initial findings predicted the treatment dependence. More than 20% of patients experienced sustained hemosiderosis and/or adverse effects of PSL. The ages and reticulocyte counts at diagnosis of the patients who underwent HSCT were lower than in the patients who did not. HSCT led to the highest success (85%) of all previous reports, even though 5 alternative donors were included in our study. Two cord blood transplants from unrelated donors failed. These findings suggest the need for developing an integral treatment strategy including selective HSCT for refractory DBA.

Increased Deoxycytidine Kinase mRNA Level After Treatment with Interleukin-3.

Pretreatment of IL-3 to Kasumi-1 human acute myeloid leukemia cells enhanced 1-B-D-arabinofuranosyl cytosine (ara-C) cytotoxicity 1.2. to 1.4-fold (median 1.3). To clarify the mechanism of interleukin-3 (IL-3) on ara-C cytotoxicity, we investigated the level of deoxycytidine kinase mRNA with the competitive polymerase chain reaction method and enzyme activities, the incorporation of [(3)H] ara-C into DNA and intracellular ara-cytidine triphosphate (CTP) levels with high-performance liquid chromatography and analyzed cell cycles. The level of deoxycytidine kinase mRNA showed a fourfold increase (88.3 plus minus 4.33 amol &mgr;g of total RNA) at 3 days after treatment with IL-3 compared to control (20.3 plus minus 4.33 amol &mgr;g). After IL-3 treatment, ara-C incorporation into the DNA was increased to 1.33 to 1.83-fold (median, 1.73-fold). The G0/G1 late-phase and S-phase percentages of cells were increased from 28.99 to 78.73% in the IL-3 treatment group as compared to control. These results indicate that IL-3 pretreatment increases the level of deoxycytidine kinase mRNA and ara-C incorporation into the DNA and also increases ratios of G0/G1 late-phase and S-phase subsequent to an enhancement of ara-C cytotoxicity against leukemia cells.

Surgical treatment and perioperative management of moyamoya disease associated with glycogen storage disease Type 1a.

The authors report a case of concurrent moyamoya disease and glycogen storage disease Type 1a that was successfully managed with bypass surgery. This 7-year-old Japanese girl, diagnosed with glycogen storage disease Type 1a at the age of 2 years, presented with repeated transient ischemic attacks. Cerebral angiography revealed severe stenosis at the terminal portions of the bilateral internal carotid arteries, with typical moyamoya vessels. The patient underwent superficial temporal artery-middle cerebral artery anastomosis and encephalomyosynangiosis bilaterally, in 2 staged procedures at an interval of 4 months. Despite perioperative administration of glucose, hypoglycemia and metabolic acidosis occurred after both surgeries. The symptoms were milder after the second surgery, in which an increased dose of glucose was used. The patient tolerated the perioperative conditions well under intensified medical treatment, and no further ischemic symptoms occurred.

Combined antitumor effect of cyclophosphamide and bromodeoxyuridine in BDF1 mice bearing L1210 ascites tumors.

We investigated the combined effect of cyclophosphamide (CPA) and 5-bromo-2'-deoxyuridine (BrdUrd) both in mice bearing L1210 ascites tumors and in L1210 leukemic cells in vitro. Administration of BrdUrd (100 mg/kg) for 5 consecutive days before a single dose (80 mg/kg) of CPA significantly extended the survival of mice by 158%, compared with CPA alone. BrdUrd administered at daily doses of 100 or 200 mg/kg for 5 consecutive days did not extended the survival of mice. An in vitro MTT assay revealed that BrdUrd enhanced the cytotoxic effect of 4-hydroxycyclophosphamide, an active form of CPA, in the L1210 cells. These results indicate that BrdUrd enhanced the antitumor effect of CPA both in vivo and in vitro.