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Journal of Allergy and Clinical Immunology - J ALLERG CLIN IMMUNOL. 01/2005; 115(2).
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ABSTRACT: A 7-year-old boy with prolonged and marked leukopenia diagnosed at 6 months of age is described. The polymorphonuclear cells presented no hypersegmented nuclei or concentrated nuclear chromatin, although vacuolated myeloid cells appeared in bone marrow smears. Neutrophils reversed in response to administration of G-CSF. His leukocyte counts were 400-1000/microL during afebrile periods and increased to 2000-3000/microL in response to infections. The increased leukocyte was usually neutrophils, but lymphocytes also increased at EB-virus infection. The serum IgG decreased gradually and was 364 mg/dL at 7 years of age. Antibody responses were normal and recurrent otitis media has been the patient's only problem. Granulocytopenia with hypogammaglobulinemia of this patient mimics myelokathexis with hypogammaglobulinemia, and lymphocytes also increased at viral infections.
Pediatric Hematology and Oncology 04/2000; 17(2):171-6. · 0.89 Impact Factor
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ABSTRACT: Although elevated serum levels of immunoglobulins are frequently observed in patients with chronic active Epstein-Barr virus (EBV) infection, there have been no reports concerning levels of IgG subclasses.
Serum levels of IgG subclasses were measured by the enzyme-linked immunosorbent assay (ELISA) in 30 children with severe chronic active EBV infection.
Serum levels of IgG1 were elevated in most patients, except for one who showed an abnormally low level of IgG1 and progressive hypogammaglobulinemia. Serum levels of IgG2, IgG3 and IgG4 in the patients were comparable to those in control children, while abnormally low levels of IgG2, IgG3 and IgG4 were observed in six, three and four cases, respectively.
Although not always susceptible to bacterial infections, low levels of IgG2 were frequently observed in patients with chronic active EBV infection and elevated IgG1 is responsible for the increase of serum IgG in these patients.
Pediatrics International 03/2000; 42(1):21-5. · 0.63 Impact Factor
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ABSTRACT: Although a reversed CD4/CD8 ratio and increased proportion of CD8+ HLA-DR+ T cells are well known as the characteristic immune response in infectious mononucleosis (IM), it has not been elucidated whether these immune responses are affected by patient age and pathogenetic viruses.
T cell subsets were analyzed by two-color flow cytometry using fluorescein isothiocyanate- and phycoerythrin-conjugated monoclonal antibodies in 115 infants and children aged from 4 months to 10 years with IM due to Epstein-Barr virus (EBV), cytomegalovirus (CMV) and dual infection with both viruses.
A reversed CD4/CD8 ratio and increased proportions of CD4+/HLA-DR+ T cells, CD8+ T cells and CD8+/HLA-DR+ T cells became more prominent as the age of the patients became older. No differences were observed in proportions of T cell subsets between EBV- and CMV-infection among patients aged from 6 to 17 months. Although the responses of these T cells were weak in infants with single virus infection by EBV and CMV, markedly strong T cell responses comparable with those in older children were observed in infants with EBV/CMV dual infection. Clinical symptoms were more severe in patients with EBV/CMV dual infection than those with EBV or CMV alone.
The manner of these T cell responses in the acute phase of IM was considered to be age dependent, although strong T cell responses and severe disease were observed in EBV/CMV dual infection irrespective of patient age.
Pediatrics International 11/1999; 41(5):484-9. · 0.63 Impact Factor
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Acta Paediatrica 11/1999; 88(10):1161-2. · 2.07 Impact Factor
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ABSTRACT: Chronic active Epstein-Barr virus infection (CAEBV) is a severe illness with unusual EBV activation that persists for years, and its pathogenesis is largely unknown. After the creation of an accurate and reproducible polymerase chain reaction system to quantify EBV DNA, virus loads in peripheral blood lymphocytes (PBL) were determined in 54 children: 15 with CAEBV, 16 with infectious mononucleosis (IM), and 23 healthy children. Children with CAEBV and those with IM had high virus loads. Lower loads were detected in 47% of seropositive healthy donors. There were two distinct differences between children with CAEBV and those with IM: The former had greater viral replication (10(3)-10(7) copies/2.5x10(5) PBL) than those with IM, and viral replication declined in children with IM whereas active replication persisted for years in subjects with CAEBV. Persisting high virus loads are a possible diagnostic criterion for CAEBV. EBV loads may enable classification and prognosis of EBV infections.
The Journal of Infectious Diseases 05/1999; 179(4):1012-5. · 6.41 Impact Factor
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ABSTRACT: Although anti-viral capsid antigen (VCA)-immunoglobin M (IgM) is the most reliable serological marker of primary Epstein-Barr virus (EBV) infection, it could only be detected in limited cases of infectious mononucleosis in children. We analyzed anti-EBV antibodies by an enzyme-linked immunosorbent assay (ELISA), a sensitive method for detecting IgM antibody and compared these results with those obtained by a conventional indirect immunofluorescence (IF) method.
Anti-Epstein-Barr virus early antigen (EA)-IgM and nuclear antigen 1 (EBNA1)-IgG were examined by an ELISA assay in 180 sera from 70 infants and children with infectious mononucleosis, diagnosed serologically by standard IF methods.
Although by IF, VCA-IgM was detected in only 37 of 70 (52.9%) of the sera from the acute phase of the disease, by ELISA, EA-IgM was detected in 65/70 (92.9%) of these sera. Among infants less than 12 months of age. EA-IgM was positive in 11/13 cases (84.6%) while VCA-IgM was detected in only 3/13 cases (23.1%). Anti-Epstein-Barr virus nuclear antigen 1-IgG was not detected by ELISA in the sera from the acute phase of infectious mononucleosis. Anti-EBNA was not detected by IF in about one-third of the sera during 6-8 months after onset of the disease, whereas by ELISA, EBNA1-IgG was detected in 93.0%. Sera that were positive or negative for both EA-IgM and EBNA1-IgG by ELISA were observed in several cases after the patients recovered from the disease.
Although serodiagnosis by the combination of ELISA for EA-IgM and EBNAI-IgG was more sensitive than IF methods, especially in the case of infants and young children, several patients during convalescence and recovery might be judged as seronegative or as being in highly reactivated states.
Acta paediatrica Japonica; Overseas edition 09/1998; 40(4):328-32.
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ABSTRACT: A 13 year old girl diagnosed as having chronic myeloid leukemia (CML) was treated with interferon-alpha (IFN-alpha) alone and 4 months later hematological remission was obtained. In the course of the IFN-alpha treatment there was neither infectious sign nor side effects. In this study we have examined the effect of IFN-alpha on superoxide O2- generation by polymorphonuclear neutrophils (PMN). The PMN of the patient generated less O2- than PMN from normal controls. When patient PMN were cultured in the presence of 1000 U/mL IFN-alpha, enhancement of the formyl-methionyl-leucyl-phenylalanine induced O2- generation following priming with tissue necrosis factor-alpha was observed. Over the course of the IFN-alpha therapy, such O2- generation was gradually restored. It is suggested that CML PMN are in the resting condition in terms of their ability to generate O2- and that IFN-alpha is effective in inducing O2- generation by CML PMN.
Acta paediatrica Japonica; Overseas edition 05/1995; 37(2):217-21.
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ABSTRACT: A case is reported of a female infant having multiple anomalies, including epicanthic folds, hypertelorism, bifid nasal bridge, shallow philtrum, low-set ears, brain atrophy, cleft palate, hemangioma on the chest, and reduction deformity of the left upper limb. This is the first case where an infant who was exposed to sodium valproate intra-uterine has a reduction deformity of the upper limb.
Acta paediatrica Japonica; Overseas edition 03/1995; 37(1):58-60.
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ABSTRACT: Natural killer (NK) cell activity, OK-432-augmented-NK cell activity, concentrations of interferon-gamma (IFN-gamma) in the culture supernatants of lymphocytes stimulated with OK-432, and subsets of NK cells and memory T cells were analyzed in 42 children with acute lymphoblastic leukemia (ALL) receiving maintenance chemotherapy. Natural killer and augmented-NK cell activities, and concentrations of IFN-gamma in the supernatants of cultured lymphocytes, were significantly lower in the patients with ALL than in age-matched control children. Among the NK cell subsets, proportions of CD57+ cells in the patients with ALL were significantly higher than in the controls, and proportions of a memory T cell subset (CD4+ CD29+ T cells) in the patients were also significantly higher than in the controls. These results suggest that the function of NK cells and memory T cells that are considered as IFN-gamma producing cells, may be defective in ALL, and that CD57+ cells and CD4+ CD29+ cells may be resistant to or recover rapidly from suppression by cytotoxic chemotherapy.
Acta paediatrica Japonica; Overseas edition 09/1994; 36(4):361-5.
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ABSTRACT: Three children with severe candidal infections were treated with fluconazole (FLCZ). An excellent effect or a partial effect was obtained in each case. Case 1 was a boy with candida esophagitis. He had been treated for relapsed ALL and became febrile with severe swallowing pain. FLCZ was administered intravenously and he became afebrile after 10 days of the therapy. Case 2 was a boy with candida pneumonitis. He had been treated for relapsed ALL and became febrile with diffuse infiltration in chest X-ray. FLCZ was administered intravenously and he became afebrile transiently, though fever and abnormal X-ray shadows reappeared soon and died of pneumonia and leukemic infiltrations. Case 3 was a girl with candida pneumonitis. She had been treated for relapsed neuroblastoma and became febrile and dyspneic. She was treated with intravenous FLCZ with no effects and died of pneumonia. All three patients showed positive results in 2 of 3 markers for candida infection, including, Cand-Tec, D-arabinitol and fungal index. FLCZ was well tolerated and no adverse effects or abnormal laboratory test results were observed. FLCZ was considered as an effective and safe antifungal agent in the treatment for fungal infections in children.
The Japanese journal of antibiotics 04/1994; 47(3):304-8.
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ABSTRACT: Antibodies of Epstein-Barr virus (EBV), EBV-specific cytotoxic T lymphocyte (EBVCTL) activity and the lymphocyte subset of CTL were examined in 13 Japanese children with chronic active EBV infection (CAEBV) and their parents (eight fathers and 10 mothers). Anti-virus-capsid antigen (VCA)-IgG antibody titers ranged from 1:640 to 1:5120 in the patients with CAEBV and from 1:40 to 1:640 in the parents. While anti-VCA-IgM antibody was detected in three patients, anti-VCA-IgA antibody in five and anti-early-antigen (EA)-IgG antibody in 11, no antibody was detected in the parents except anti-EA antibody, which was positive in the mothers of cases 5 and 13 (1:10 and 1:40). Anti-EBV-associated nuclear antigen (EBNA) antibody was < or = 1:10 in six out of 13 patients with CAEBV and in 10 out of 18 parents tested. Epstein-Barr virus activity was significantly lower (P < 0.005) both in the children with CAEBV and in their parents than in seropositive age-matched controls. Proportions of a CTL subset (CD8+ CD11- lymphocytes) in the patients with CAEBV were significantly higher (P < 0.005) than in controls, while those in the parents were at the same level as in controls. Defective EBVCTL activity and anti-EBNA-antibody responses were frequently observed both in children with CAEBV and in their parents, which may suggest that the abnormal immune response to EBV may be based on a familial disorder, though no familial involvement has been reported in Japanese children with CAEBV.
Acta paediatrica Japonica; Overseas edition 10/1993; 35(5):394-9.
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ABSTRACT: Serum levels of IgG subclasses were measured in 18 children with acute lymphoblastic leukemia (ALL) receiving maintenance chemotherapy and in 36 age-matched controls in order to attempt to analyse the effects of chemotherapy. The IgG subclasses were measured by enzyme linked immunosorbent assay. Serum IgG1, IgG2 and IgG4 levels in the patients were significantly (p less than 0.01, p less than 0.005, p less than 0.005) lower than in the controls, but serum IgG3 levels in patients were as high as in controls. Suppression on IgG2 and IgG4 were more profound than IgG1. In six children, the levels of the IgG subclasses were measured at diagnosis, during maintenance chemotherapy and one year after cessation of chemotherapy. The levels of the four IgG subclasses at diagnosis and after cessation of chemotherapy were as high as those in control children except for the IgG4 levels in the post-chemotherapy group. IgG2 and IgG4 may be more susceptible to suppression by chemotherapy than IgG1 and IgG3 may not be suppressed by chemotherapy.
Acta paediatrica Japonica; Overseas edition 07/1992; 34(3):278-81.
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ABSTRACT: We conducted clinical studies on panipenem/betamipron (PAPM/BP), a newly developed parenteral carbapenem antibiotic, for its clinical application in the field of pediatrics. 1. A clinical study was performed on 13 children with infections, including 6 with acute bronchopneumonia, 1 each with acute pharyngitis, acute bronchitis, sepsis, staphylococcal scalded skin syndrome, urinary tract infection, subcutaneous abscess and furuncle. PAPM/BP was administered by intravenous drip infusion. Doses varied from 12 to 27 mg/kg body weight were given t.i.d. or q.i.d. Lengths of treatment ranged from 4 to 25 days. Clinical efficacies were excellent in 3 and good in 9 cases, with an efficacy rate of 92%. 2. No adverse reactions were observed. In laboratory tests, elevations of GOT, GPT and urobilinogen were observed in 3 cases. It was concluded that PAPM/BP was a promising drug for the treatment of bacterial infections in children.
The Japanese journal of antibiotics 05/1992; 45(4):437-42.
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ABSTRACT: Serum levels of IgG subclasses were analysed in 15 children with acute lymphoblastic leukemia (ALL) receiving maintenance chemotherapy and 10 children with aplastic anemia and autoimmune diseases receiving prednisolone therapy longer than 2 months (Steroid group). The results were as follows. Serum levels of IgG1 in ALL were significantly (p less than 0.05) lower than age matched normal controls, while the IgG1 levels in the Steroid group were as high as in normal controls. Serum levels of IgG2 in ALL and the Steroid group were significantly (p less than 0.005, p less than 0.02) lower than in normal controls. Serum levels of IgG3 in ALL and the Steroid group were as high as in normal controls. Serum levels of IgG4 in ALL and the Steroid group were significantly (p less than 0.005, p less than 0.05) lower than in normal controls. IgG2 and IgG4 should be more susceptible to suppression by immunosuppressive chemotherapy than IgG1, and IgG3 would hardly suppressed by immunosuppressive chemotherapy.
[Rinshō ketsueki] The Japanese journal of clinical hematology 01/1991; 31(12):1920-3.
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ABSTRACT: Therapeutic effects of cefodizime (CDZM, THR-221), a new cephalosporin having a methoxyimino group, were examined in various infectious diseases in children. Clinical efficacy rates were 100% (3/3) in pneumonia, 100% (5/5) in acute bronchitis, 75% (3/4) in upper respiratory infections and 100% (1/1) in each of a croup and a mixed infection with Streptococcus pyogenes and staphylococcal impetigo. Hence, the overall efficacy rate was 92.9% (13/14). Adverse effects were observed in 2 cases, i.e. exanthema provably due to drug allergy in 1 case and a slightly elevated GPT in another. Changes in serum concentrations and urinary excretion of CDZM were examined in a child with no infection. T 1/2 values obtained were 124.5 minutes (bioassay) and 143.4 minutes (high performance liquid chromatography (HPLC]. Eight hour recovery rates in urine were 62.9% (bioassay) and 65.4% (HPLC). CDZM was considered to be a safe and useful drug in treating various infectious diseases in children.
The Japanese journal of antibiotics 07/1989; 42(6):1414-23.
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ABSTRACT: Sulbactam (SBT) is a new derivative of the basic penicillin nucleus. It effectively and irreversibly inhibits several important bacterial beta-lactamases and displays synergistic effects against the resistant organisms when co-administered with ampicillin (ABPC). SBT/ABPC, which is a fixed combination of SBT and ABPC in a 1:2 ratio, was studied for clinical efficacy in the field of pediatrics. Patients treated were infants and children ranging from 12 days to 13 years and 2 months old suffering from acute tonsillitis in 2 cases, acute bronchitis in 2 cases, septicemia in 2 cases, acute enteritis, acute pyelonephritis and osteomyelitis in 1 case each, a total of 9 cases. SBT/ABPC was administered 100-300 mg/kg in daily doses and durations of treatment ranged from 4 to 17 days. Clinical results were "excellent" in 6 and "good" in 2: the efficacy rate was 88.9% or 8 cases out of 9. Neither clinical side effects nor abnormal laboratory findings obviously attributable to SBT/ABPC were observed in any cases.
The Japanese journal of antibiotics 04/1989; 42(3):766-72.
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ABSTRACT: We have evaluated sultamicillin (SBTPC) fine granules for pharmacokinetics and therapeutic effectiveness in children. The results are summarized as follows. 1. Pharmacokinetic parameters after the oral administration of single dose of 5.0 mg per kg body weight in 1 child were as follows: The peak serum concentrations of ampicillin (ABPC) and sulbactam (SBT) were 1.92 micrograms/ml at 1 hour and 1.85 micrograms/ml at 1 hour, respectively. The half-lives in serum and urinary excretion rate for ABPC and SBT were similar. 2. A clinical study was performed on 15 children with infections, including 4 with tonsillitis, 5 with pharyngitis, 2 each with bronchitis, cystitis, and urinary tract infections. Doses ranging from 6.7 to 18.2 mg/kg body weight were given tid. or qid. Lengths of treatment ranged from 5 to 10 days. The therapeutic responses were considered "excellent" in 6 and "good" in 9, with an effectiveness rate of 100%. 3. As to side effects of the drug, diarrhea was observed in 1 patient. It was concluded that SBTPC was a promising drug for the treatment of bacterial infections in children.
The Japanese journal of antibiotics 01/1989; 41(12):1973-9.
