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Biomedical subjects

Kousaku Matsubara

Publications and source records attributed to Kousaku Matsubara.

18 recordsLinked to original sources

Recurrence of occult pneumococcal bacteremia by an identical strain in an apparently healthy child.

This is the first report to describe an apparently healthy girl, who developed recurrent occult bacteremia by the same Streptococcus pneumoniae strain, at 11 and 15 months of age. The two separately isolated organisms were demonstrated to have the identical serotype (type 6B), antibiotic susceptibility (intermediately penicillin-resistant), genotypes of penicillin-binding proteins, and patterns of pulse-field gel electrophoresis. The serum levels of anti-type 6B antibodies showed poor responses after both bacteremic episodes, but other immunological workups did not demonstrate any abnormalities. This case indicates that occult bacteremia may recur due to an identical pneumococcal strain in an immunocompetent infant, and that early introduction of pneumococcal conjugate vaccine is necessary in Japan.

Antibodies, Bacterial↗

Three fatal cases of invasive serotype VI group B streptococcal infection.

Serotype VI group B Streptococcus (GBS) has been almost frequently isolated among colonizing strains of pregnant women in Japan, but the clinical features and prognosis, when a patient is invasively infected, are largely unknown. We report, for the first time, three cases of fatal infection caused by serotype VI GBS; two cases were middle-aged men with necrotizing fasciitis/cellulitis, sepsis, and toxic shock syndrome with poorly controlled diabetes as underlying conditions; and one was a premature infant with intrauterine infection. Our results indicated that type VI GBS is pathogenic for humans not only in fetuses but also adults, and has the ability to be fatal, at least in selected patients.

Abortion, Septic↗

[Osteonecroses of the bilateral tali during maintenance therapy in a child with acute lymphoblastic leukemia].

We present a 12-year-old girl with acute lymphoblastic leukemia (ALL) complicated by osteonecroses of the bilateral tali. She was diagnosed as having ALL at 11 years old and was classified as extremely high risk ALL according to the criteria of Japan Association of Childhood Leukemia Study. She complained of pain around the bilateral ankles during maintenance therapy on 86-88 and 96-98 weeks. Magnetic resonance imaging study demonstrated osteonecroses of bilateral tali. Nonweight-bearing (crutches and wheelchair) over 1 year did not improve osteonecrotic lesions. She had all of the recently identified risk factors for osteonecrosis, including higher cumulative dose of corticosteroid, female gender, age over 10 years, and specific genetic polymorphisms (2/2 enhancer repeat genotype of thymidylate synthase, C/C genotype of vitamin D receptor start site). Early indication of ALL patients predisposed to genetic, treatment-related risk factors for osteonecrosis and appropriate preventive strategy for such patients await a further multicenter study in Japan.

Antineoplastic Agents↗

Thrombopoietin in the cerebrospinal fluid of patients with aseptic and bacterial meningitis.

Despite the recent evidence of the localization of thrombopoietin (TPO) and its receptor in the central nervous system (CNS), TPO protein concentrations in the cerebrospinal fluid (CSF) remained to be clarified. We previously reported that serum TPO is increased in children with meningitis. To determine changes in TPO concentrations in the CSF by meningitis and to explore the relationship between serum and CSF TPO concentrations, we measured TPO concentrations in 110 CSF samples and 33 serum/CSF pairs from 11 bacterial meningitis, 49 aseptic meningitis, and 50 nonmeningitis children. In only 12% (13 of 110) of CSF samples (0 bacterial meningitis, 8 aseptic meningitis, and 5 controls), TPO concentrations could be determined (24.1 +/- 29.0 pg/ml). CSF TPO concentrations did not significantly differ among the three groups and did not correlate with age. TPO concentrations in all serum samples were detectable, and mean concentrations in bacterial meningitis (510.6 +/- 237.0 pg/ml) were significantly higher than those in aseptic meningitis (136.6 +/- 71.6, p < 0.01) and controls (181.3 +/- 88.3, p < 0.01). These findings suggest that TPO is not produced in the CNS of patients with meningitis and that TPO did not cross the blood-brain barrier even during meningeal infection.

Adolescent↗

[Childhood acute lymphoblastic leukemia with t(1;19) lacking E2A-pBX1 chimeric transcripts].

We present a pediatric case of acute lymphoblastic leukemia (ALL) with chromosomal translocation 1;19 lacking E2A-PBX1 chimeric transcripts. On admission, the patient showed remarkable splenomegaly. Laboratory findings demonstrated that WBC was 12900/microl with blasts 61.5%. Bone marrow examination revealed 1282 X 10(3)/microl of the nucleated cell count with 95.5% lymphoblasts. Surface marker analysis showed an early pre-B lineage immunophenotype (CD10+, CD19+, CD34+, surface Ig-). Although G-banding chromosomal analysis showed 46,XY,der(19)t(1;19)(q23;p13), E2A-PBX1 chimeric transcripts and E2A gene rearrangement were not detected with the polymerase chain reaction method and Southern blot analysis, respectively. The patient was assigned to high-risk ALL according to the criteria of the Japan Association of Childhood Leukemia Study. His clinical response to prednisolone monotherapy for the initial 7 days and subsequent multidrug chemotherapy was excellent, and he achieved complete remission on day 15, which has lasted for more than 30 months. We reviewed the bibliography of the clinical and biological features of 17 children with t(1;19)+E2A-PBX1- ALL including this case. The two prominent characteristics included an early pre-B immunophenotype (11/13) and hyperdiploid (>50 chromosomes) chromosome abnormality (8/14). However, there was substantial heterogeneity in the demographic features and prognosis. Further accumulation of such patients will facilitate the determination of the appropriate treatment for childhood t(1;19)+E2A-PBX1- ALL.

Adolescent↗

Age-dependent changes in the incidence and etiology of childhood thrombocytosis.

To determine the incidence and etiology of childhood thrombocytosis, over 15,000 platelet counts in 7,539 patients performed at a single regional hospital were reviewed. When thrombocytosis was defined as > or =500 x 10(9)/l of platelet counts, the condition could be diagnosed in 6.0% (456 cases) of the patients. All patients were classified as having secondary thrombocytosis. The incidence of thrombocytosis dramatically changed throughout child development; it was 12.5% in neonates, peaked to 35.8% in 1-month-old infants and then returned to 12.9% in 6- to 11-month-old infants. Thereafter, it gradually decreased with age to only 0.6% in 11- to 15-year-old children. Frequent causes of thrombocytosis included infection (67.5%), Kawasaki disease (9.4%), prematurity (7.7%) and iron deficiency anemia (6.4%). Thrombocytosis was an incidental finding in a substantial population of early infants. Thrombocytosis as a reaction to several types of infection and Kawasaki disease was more common in children under 7 years old, while autoimmune disease and tissue damage were major causes in children aged 11-15 years. No child had thromboembolic complications. These findings indicate that childhood thrombocytosis is a benign condition and its incidence and etiology seem to depend on age.

Adolescent↗

[FISH detected 11q23 microdeletion and translocation at the long arm of chromosome 11 in a child with normal karyotypic acute lymphoblastic leukemia].

We report on a 6-year-old girl with acute lymphoblastic leukemia (ALL) with 11q23 microdeletion and translocation at the long arm of chromosome 11, which were detected by fluorescence in situ hybridization (FISH) but not by conventional cytogenetics. She was hospitalized because of fever and generalized bone pain. Results of peripheral blood examination included a WBC of 5,400/microliter with 12% lymphoblasts. Bone marrow studies showed 75% of early pre-B lineage lymphoblasts with L1 morphology. G-banding chromosome analysis demonstrated a normal karyotype. However, FISH using mixed lineage leukemia (MLL) and 11q subtelomere probes demonstrated 11q23 microdeletion and translocation at the long arm of chromosome 11 to an undefined chromosome. MLL rearrangement was not detected by Southern blotting analysis. The patient achieved complete remission 15 days after receiving high-risk group chemotherapy of the Kyoto University Pediatric Hematology/Oncology Study Group and has remained in complete remission for more than 30 months. Since MLL/11q23 abnormalities confer a poor prognosis in childhood ALL, the accurate detection of such abnormalities is of paramount significance in assigning individual cases to risk categories. The findings from the present case and recent literature indicate that the FISH-based approach is complementary to conventional cytogenetics, and should be systematically used in childhood ALL at diagnosis.

Antineoplastic Combined Chemotherapy Protocols↗

Serum immunoglobulin levels at onset: association with the prognosis of childhood idiopathic thrombocytopenic purpura.

Between 1981 and 2000, 87 patients with new diagnoses of idiopathic thrombocytopenic purpura (ITP) were admitted to the pediatric department of Kobe City General Hospital or Nishi-Kobe Medical Center. The patients' clinical records were analyzed for the relationships of disease outcome to serum immunoglobulin levels and other factors, including sex, onset age, and initial platelet counts. The disease of 22 patients became chronic, and of the 65 patients with an acute form of the disease, 27 exhibited levels of immunoglobulin G (IgG), IgA, or IgM above the 97.5% confidence limits of the age-matched control subjects. However, only 2 patients with the chronic form of the disease showed elevated serum immunoglobulin levels. The presence of antecedent specific viral infections was also associated with the acute disease form. In predicting the prognosis of childhood ITP, high serum immunoglobulin levels at initial presentation can be considered a good prognostic marker for the acute form of the disease.

Acute Disease↗

A randomized study of two long-course prednisolone regimens for nephrotic syndrome in children.

BACKGROUND: Long-course prednisolone regimens have been shown to be more effective than short-course regimens in sustaining remission of nephrotic syndrome in children. However, the most beneficial approach among the long-course regimens remains unknown. METHODS: Seventy-three children with new-onset nephrotic syndrome were allocated at random to the two long-course regimens and followed up for 2 years. Group A was administered prednisolone at a daily dose of 60 mg/m2 for 6 weeks, followed by an alternate-day dose of 40 mg/m2 for 6 weeks (the long daily regimen). Group B was administered the same daily dose for 4 weeks, followed by an alternate-day dose of 60 mg/m2 for 4 weeks, and doses were tapered by 10 mg/m2 every 4 weeks (the long alternate-day regimen). RESULTS: Group B had a lower incidence of corticosteroid toxicities than group A during the initial treatment. Kaplan-Meier analysis of the sustained remission rate of the two treatment groups showed a marginally significant difference (P = 0.069) and showed a significant difference when patients were stratified for age of disease onset (P = 0.048). In a subgroup of younger children (<4 years at onset), group B had a greater rate of sustained remission (P < 0.01) and fewer children with frequent relapses (P < 0.05) than group A, whereas in older children (> or =4 years at onset), both groups had similar good sustained remission rates. CONCLUSION: These findings collectively indicate that the long alternate-day regimen may be more beneficial, with less corticosteroid toxicities, than the long daily regimen, and children with younger age at disease onset may be susceptible to relapse and especially benefit from the long alternate-day regimen for sustaining remission of the disease.

Adolescent↗

[A case of group B streptococcal occult bacteremia].

We reported an infant with occult bacteremia caused by group B Streptococcus (GBS). An 8-week-old girl, who was uneventfully born to an 18-year-old mother, was hospitalized because of a 4-hour history of fever. On admission, she appeared nontoxic, and the temperature was 39.0 degrees C, and the pulse and respiratory rates were 162/min and 42/min, respectively. Laboratory findings showed a total white blood count of 5,200/microliter with 44% neutrophils and C-reactive protein of 0.7 mg/dl. Cerebrospinal fluid and urine examinations did not disclosed any abnormalities. After a complete evaluation of sepsis including cultures from blood, cerebrospinal fluid, urine, stool, and throat swab, intravenous cefotaxime was administered at 100 mg/kg/day in three fractions. Nine hours after the start of the culture, GBS was isolated from blood, and thereafter from the throat, but not from other culture sites obtained on admission. However, at that time she fed well and her temperature was subsiding. Forty-eight hours after admission, she became afebrile and cefotaxime administration was continued for 7 days. Based on the examinations of minimal inhibitory concentrations of various antibiotics, serotype analysis, and restriction-digestion patterns of genomic DNA, the 3 GBS strains isolated from the patient's blood and throat and the maternal anus were identical, suggesting that the infant was infected by her mother. This is the first report in Japan describing the clinical course of GBS occult bacteremia. According to a case series published in the English literature and our case, there are few clinical and laboratory markers predictive for GBS occult bacteremia, but this condition may develop focal invasive infections. A high index of suspicion is required for correct diagnosis. Further accumulation of such patients is warranted to establish the appropriate treatment.

Bacteremia↗

[Salmonella enteritidis osteomyelitis of the tibia--a case report and review of literature on Salmonella osteomyelitis of Japanese patients].

We described a rare case of Salmonella enteritidis osteomyelitis of the tibia combined with arthritis of the ankle joint. A 4-year-old, otherwise healthy girl was hospitalized with 9-day history of fever, left leg pain, and diarrhea. On admission, her left lower leg and ankle were markedly reddened and swollen. Laboratory examinations disclosed a WBC of 16,300/microliter and a C-reactive protein of 15.6 mg/dl. A T2-weighed magnetic resonance image of the leg depicted a high intensity area around the left distal tibia and an extremely high intensity fluid in her left ankle joint, leading to our diagnosis of purulent osteomyelitis of the tibia and arthritis of the ankle joint. Salmonella enteritidis was isolated from ankle joint fluid and later aspirated bone marrow of the tibia, but not from blood or stool. Because of poor response to intravenous treatment with panipenem/betamipron for 2 days, she underwent drainage and washing of the joint fluid, and intramedullary administration of cefotaxime and ampicillin. She completely recovered without sequelae following treatment with sensitive antibiotics for 4 weeks in total. There has not been any relapse for more than 1.5 years. The authors also bibliographically surveyed the literature published from 1966 to 2002 and found 35 Japanese patients with Salmonella osteomyelitis. The present patient was the second case caused by Salmonella enteritidis in Japan. Septic arthritis is a rare complication, accounting for only 8% of the patients. Since Salmonella enteritidis has been a leading serotype among human isolates of Salmonella species during the past decade, it would be warranted to determine whether osteomyelitis due to this organism is likely to increase.

Child, Preschool↗

Seroepidemiologic studies of serotype VIII group B Streptococcus in Japan.

Levels of antibody to serotype VIII group B Streptococcus (GBS) were surveyed in serum samples from 583 pregnant women, from 461 neonates born to these women, and from 4 mother-and-neonate pairs with early-onset serotype VIII sepsis. Colonization by serotype VIII GBS was associated with significantly higher serum concentrations of serotype-specific antibodies (geometric mean [GM], 5.53 micro g/mL), compared with both noncolonization (1.53 micro g/mL) and colonization with other serotypes (2.19 micro g/mL). There was excellent correlation between antibody levels in mothers and those in their neonates. The prevalence of positive antibody levels, when arbitrarily defined, according to antibody levels in neonatal sepsis (GM, 0.49 micro g/mL) as >1.0 micro g/mL, was 58% of all pregnant women and 85% of the women colonized by serotype VIII. This high serotype prevalence may explain, at least in part, why serotype VIII causes early-onset neonatal disease at rates lower than those which would be expected on the basis of its prevalence in mothers in Japan who are colonized by GBS.

Adult↗

Acute coalescent mastoiditis and acoustic sequelae in an infant with severe congenital neutropenia.

We report a 2-month-old boy with severe congenital neutropenia (SCN), who developed acute necrotizing otitis media and coalescent mastoiditis due to methicillin-sensitive Staphylococcus aureus. The infection fulminantly progressed within a day to a subtotal perforation of the tympanic membrane, destructive bony changes of ossicles, lateral subperiosteal abscess, and suppurative labyrinthitis. Despite the combined treatment with intravenous antibiotics and granulocyte colony-stimulating factor, the infection resulted in mixed hearing impairment. Much attention should be given to prompt diagnosis of otomastoiditis in SCN, a rare congenital disorder, since resultant acoustic sequelae may affect subsequent speech development and intellectual ability.

Acute Disease↗

Elevation of serum thrombopoietin precedes thrombocytosis in acute infections.

To clarify the mechanisms underlying thrombocytosis secondary to infections, we longitudinally studied serum levels of thrombopoietin (TPO) and interleukin (IL)-6 in 15 infants and young children with prominent thrombocytosis (platelets >700 x 10(9)/l) following acute infections and 116 age-matched controls using an enzyme-linked immunosorbent assay. The subjects included nine patients with bacterial infections, three with viral infections and three with non-determined pathogens. TPO values in the controls were 2.24 +/- 0.87 fmol/ml (mean +/- SD) with a 95% reference interval of 0.85-4.47 fmol/ml. In the first week of infection, platelet counts were normal, but TPO values increased (approximately 10.73 fmol/ml). TPO levels peaked on day 4 +/- 2 at 6.44 +/- 2.37 fmol/ml and then fell gradually. When platelet counts peaked in the second and third weeks, TPO levels were similar to the controls. IL-6 levels in the first week rose and dropped more rapidly than TPO. Serum TPO values were significantly correlated with C-reactive protein levels (r = 0.688, P < 0.001) and IL-6 levels (r = 0.481, P = 0.027). These results suggest that TPO contributes to thrombocytosis following infections in conjunction with IL-6, arguing for additional regulatory mechanisms of blood TPO levels.

Acute Disease↗

Acute lymphoblastic leukemia with coexpression of CD56 and CD57: case report.

The authors present the clinical profile of a 6-year-old girl with an unusual immunophenotype of acute lymphoblastic leukemia (ALL). At the initial presentation, massive hepatosplenomegaly developed. The leukemic cells were myeloperoxidase-negative and morphologically lymphoblastic. These cells were positive for B-precursor-cell (CD10, CD19) antigens and natural killer cells (CD56, CD57). Rearrangements of both immunoglobulin heavy chain alleles and monoallelic rearrangement of T-cell receptors (TCRs)-beta and -delta genes, but not that of TCR-gamma gene, were detected, suggesting that these cells being of B-precursor origin. The patient received chemotherapy for extremely high-risk ALL with a good response. To the authors' knowledge, this is the first pediatric case describing coexpression of CD56 and CD57 on B-lineage ALL.

Antigens, CD↗