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Biomedical subjects

E Azuma

Publications and source records attributed to E Azuma.

At least 73 records · Page 4Linked to original sources

[Pharmacokinetic and clinical studies of cefozopran in the field of pediatrics].

Cefozopran (CZOP) was administered intravenously to 22 infants (aged 3 months to 15 years) with infections excluding suppurative meningitis in doses of 10 to 40 mg/kg 3 to 4 times daily for periods of 3 to 16 days and its efficacy and safety in infantile infections as well as pharmacokinetic parameters were determined. The half-lives of CZOP after intravenous administration at doses of 10, 20 and 40 mg/kg were 2.84, 2.36 +/- 0.67, and 2.48 hours, respectively. The rates of recovery in the urine within 6 hours of administration were 83.6%, 62.9 +/- 23.1%, and 77.3%, respectively. The subjects for whom drug responses were evaluable consisted of 1 case of suppurative meningitis, 8 cases of respiratory tract infection, 2 cases of urinary tract infection, 2 cases of oral infection, 2 cases of pharyngotonsillitis, 1 case of skin soft tissue infection, and 1 case of external otitis, totaling 17 cases. The efficacy rate was 88.2%. The drug proved so effective on suppurative meningitis in particular that the patient was healed without leaving any sequela behind. Seven strains were identified as causative pathogens (5 strains of Haemophilus influenzae, 1 strain of Staphylococcus aureus, 1 strain of group B Streptococcus) isolated from 6 patients. All but 1 strain were eradicated (the rate of eradication 83.3%). In the patients with suppurative meningitis the bacterial count of spinal fluid was markedly decreased 6 hours after drug administration and the organism was eradicated in 45 hours. Eruption was noted in 1 patient as a side effect of CZOP, but disappeared soon after discontinuation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Clinical efficacy of arbekacin in patients with methicillin-resistant Staphylococcus aureus infections. Research Group of MRSA Forum].

We investigated the clinical efficacy of arbekacin (ABK) in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections, and also studied coagulase types, beta-lactamase producing activity and drug sensitivity of MRSA isolated from various clinical specimens. A total of 23 patients with MRSA infections (13 cases of pneumonia, 1 case of sepsis, 1 case of pneumonia and sepsis and 8 cases of the others) who were hospitalized from April 1992 to September 1993 were enrolled in this study. They were 14 males and 9 females, and the mean age was 66.9 years (range, 18-91 years). All patients had underlying diseases (mainly malignant tumors and cerebrovascular diseases). ABK was given intravenously at doses ranging from 75 to 100 mg twice daily. The clinical efficacy rate was 90%; 8 cases showed excellent responses, 10 cases good, 1 case fair, 1 case poor and 3 cases were unevaluable. The eradication rate of MRSA was 81.8%; 16 cases were judged as eradicated, 3 cases decreased, 2 cases replaced, 1 case unchanged and in 1 case the bacteriological response was unknown. Side effects were not observed, but S-GPT was elevated in 1 case. Coagulase types of MRSA (123 strains) isolated at the institutes involved in the study were type II (56 strains), type IV (12 strains), type VII (13 strains) and other types (2 strains), but coagulase types of 40 strains could not be determined. Eighty-four strains (68.3%) produced beta-lactamases. MICs of ABK were 0.5 microgram/ml against 43 strains and 1 microgram/ml against 37 strains, and all of the MICs were under 4 micrograms/ml. In summary, ABK showed high antimicrobial activity against MRSA and clinical usefulness in the infections investigated.

Adolescent↗

[Experience of fluconazole granules and injection in pediatric patients].

Fluconazole (FLCZ) is an antifungal agent of triazole class and has been proven to be effective against deep-seated mycosis caused by Candida spp., Aspergillus spp. and Cryptococcus spp. This time, as we had an opportunity to use fluconazole granules, a new dosage form of the agent, we investigated its efficacy and safety in children with deep-seated mycosis together with the efficacy of the injectable form of the agent. FLCZ was administered to 6 patients with fungal infections for treatment and 5 compromised hosts with a high risk of fungal infections for evaluation of its prophylactic effect. The patients enrolled in the study were 11 in total, of whom 6 patients were evaluated for efficacy: fungal phlegmon in 2, esophageal candidiasis in 2, fungal bronchitis in 1 and oral mycosis in 1. Causative fungi for those infections were Candida albicans in 4 patients, Aspergillus, fumigatus in 1 and Aspergillus flavus in 1. The clinical efficacies were excellent in 3 patients and good in 3. The mycological efficacies were rated as eradicated in 5 patients and reduced in 1. In 5 patients to whom FLCZ was given prophylactically, development of neither fungal infection nor unknown fever was noted. No side effects nor clinical laboratory abnormalities were observed during treatment with either granules or injection, indicative of its safety in children.

Administration, Oral↗

Tyrosine phosphorylation and intracellular alkalinization are early events in human neutrophils stimulated by tumor necrosis factor, granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor.

Tumor necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte CSF (G-CSF) primed human neutrophils for enhanced release of superoxide in time- and dose-dependent manners. The priming effects of these cytokines were detected at 3 min and maximal at 10 min of preincubation. The potency of the maximal effect was TNF > GM-CSF > G-CSF. Exposure of human neutrophils to TNF, GM-CSF and G-CSF resulted in tyrosine phosphorylation of a 42-kDa protein and intracellular alkalinization in a dose-dependent manner. The dose-response curves for triggering of tyrosine phosphorylation and intracellular alkalinization by each cytokine were similar to those for priming the cells. The potency of the maximal effect on tyrosine phosphorylation was TNF > GM-CSF > G-CSF, whereas that on intracellular alkalinization was GM-CSF > TNF > G-CSF. Tyrosine phosphorylation was detected at 3 min and maximal at 5-10 min after stimulation with each cytokine. Tyrosine phosphorylation induced by TNF declined at 20-40 min, whereas that induced by GM-CSF or G-CSF was maintained for at least 40 min. Intracellular alkalinization induced by each cytokine required a lag time of 3-5 min and was sustained for at least 40 min. Tyrosine phosphorylation preceded or occurred concomitantly with intracellular alkalinization and priming of the cells. These findings indicate that tyrosine phosphorylation and intracellular alkalinization are early events in human neutrophils stimulated by TNF, GM-CSF and G-CSF, and that these early events may, at least in part, mediate activation or priming of human neutrophils by these cytokines.

Dose-Response Relationship, Drug↗

Ten-year survey of the intellectual deficits in children with acute lymphoblastic leukemia receiving chemoimmunotherapy.

Effects of chemoimmunotherapy, including cranial irradiation for central nervous system (CNS)-directed therapy, on children with acute lymphoblastic leukemia (ALL) were investigated. Fifty-five children with ALL in continuous complete remission (> 5 yr) and without evidence of current or past CNS diseases were evaluated in this retrospective study. Using standard measures of intelligence (IQ), we repeatedly (1-4 times/person; mean 2.1 times) evaluated IQ in the cohort of patients for the mean follow-up time of 9.7 yr, ranging from 5.4 to 15.8 yr. Fifty-five patients received the total number of 118 IQ testings and 40 patients received them more than twice. Patients were examined periodically at intervals of 1.4 to 10.0 yr (mean 4.8 yr) following diagnosis. Most of the published studies dealt with single IQ testing, and long-term follow-ups were not enough to assess the consequent IQ change. This report confirms and extends the previous findings: decreased IQ was related to age at diagnosis and irradiation (< 5 yr of age at diagnosis), irradiation-examination interval, and female sex. Further long-term follow-up study will be needed in these groups, since their IQs are still on the decline even after 10 yr of diagnosis.

Adolescent↗

Low R-wave amplitude in the right precordial leads in children with symptomatic doxorubicin cardiomyopathy.

Electrocardiographic (ECG) findings were studied in four patients with doxorubicin cardiomyopathy. In all patients with congestive heart failure (CHF), the ECGs had a low R-wave and low R/S ratio in lead V1. Our study suggests that increased injury to myocardial cells in the regions of the anterior septum and anterior left ventricular wall may be important in the pathogenesis of doxorubicin cardiomyopathy. Eight years later, cardiac recovery from CHF occurred with a normal ECG and left ventricular ejection fraction in one patient, indicating that CHF may be reversible in certain cases.

Antineoplastic Combined Chemotherapy Protocols↗

Role in growth regulation of cytokines and cytokine receptors in acute lymphoblastic leukaemia expressing myeloid markers.

The biological roles of cytokines and cytokine receptors were examined in acute lymphoblastic leukaemia cells expressing myeloid antigens (My+ ALL). Interleukin-3 (IL-3), granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), and low molecular-weight B-cell growth factor (LW-BCGF) could induce DNA synthesis in certain cases of My+ ALL. Whereas in My- ALL the stimulatory effects were shown only with LW-BCGF. Acute myelogenous leukaemia (AML) cells were activated with multiple cytokines including interleukin-1 (IL-1), IL-3, G-CSF and GM-CSF. Specific receptors for IL-1 and IL-3 were strongly expressed on both My+ and My- ALL cells. These receptors, however, were weakly detectable on AML cells. Additionally we studied the production of tumour necrosis factor-alpha and IL-1 by leukaemic blasts and found that distinct amounts of both cytokines were released from My+ ALL cells and AML cells, but not from My- ALL cells. The profiles of cytokines and cytokine receptors expressed by My+ ALL showed both similarities and differences to those in My- ALL or AML. The proliferation of My+ ALL cells was dependent on multiple cytokines that would regulate growth and maturation in a lineage-restricted fashion. These data suggested that My+ ALL cells might originate from uncommitted haematopoietic precursor cells coexpressing features of both lymphoid and myeloid lineages.

Antigens, CD↗

Moyamoya disease associated with bilateral renal artery stenosis.

Recent research has suggested that an association exists between moyamoya disease and fibromuscular dysplasia which involves systemic vessels, including renal arteries. We report a 3 year old girl with moyamoya disease associated with bilateral renal artery stenosis. This case may support the common etiology of these two clinical conditions. To our knowledge this is the youngest case of moyamoya disease associated with bilateral renal artery stenosis.

Aortography↗

[Clinical evaluation of S-1108 in children].

We administered S-1108 to 16 children with ages ranging from 7 month to 15 years at doses between 1.8 and 6.0 mg/kg x 3/day for 3 to 13 days. We evaluated the efficacy and safety of S-1108 in 11 children with respiratory tract infections, 3 urinary tract infections, and 2 skin infections. The efficacy rate of S-1108 was 100% and bacteriological eradication rate was 83.3%. No adverse effects were observed. These results suggested that S-1108 could be used safely in children.

Adolescent↗

Rapid priming of human monocytes by human hematopoietic growth factors: granulocyte-macrophage colony-stimulating factor (CSF), macrophage-CSF, and interleukin-3 selectively enhance superoxide release triggered by receptor-mediated agonists.

The effects of hematopoietic growth factors on human monocyte superoxide (O2-) release were investigated by using purified human monocytes in suspension. Among growth factors studied, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage-CSF (M-CSF), and interleukin-3 (IL-3) primed human monocytes and enhanced O2- release stimulated by the receptor-mediated agonists, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and concanavalin A (Con A), but not by phorbol myristate acetate, which bypasses the receptors to stimulate the cells. The optimal priming was obtained by pretreatment of cells with 1 to 5 ng/mL (0.07 to 0.34 nmol/L) GM-CSF, 50 to 100 ng/mL (0.5 to 1.1 nmol/L) M-CSF, or 10 to 20 ng/mL (0.6 to 1.3 nmol/L) IL-3 for 10 minutes at 37 degrees C. Potency of the maximal priming effects on FMLP- or Con A-induced O2- release was GM-CSF greater than M-CSF = IL-3. The combination of the optimal concentrations of any two CSFs resulted in the effect of more potent priming agent alone. Enhancement of O2- release by GM-CSF was observed over the complete range of effective concentrations of FMLP (10(-8) to 10(-6) mol/L). The pretreatment of monocytes with granulocyte-CSF (50 ng/mL), interferon-gamma (1,000 U/mL), or IL-4 (20 ng/mL) for 10 minutes at 37 degrees C had no effect on O2- release stimulated by FMLP or Con A. These findings show that GM-CSF, M-CSF, and IL-3 selectively enhance O2- release in human monocytes triggered by receptor-mediated agonists after short-term preincubation.

Adult↗

Acute megakaryoblastic leukemia with translocation t(1;22)(p13;q13) in a 10-week-old infant.

A 10-week-old girl without Down syndrome developed an acute megakaryoblastic leukemia (AMKL). Bone marrow aspirates and biopsy showed megakaryoblastic infiltration with myelofibrosis. The diagnosis was made based on the findings that the positive reactions of leukemic cells to platelet peroxidase and to monoclonal antibodies which recognize platelet-specific surface glycoprotein (GP) IIb/IIIa and GP78. The blasts also showed myeloid and monocytoid differentiation antigens. The leukemic cells had a karyotype of 46,XX,t(1;22)(p13;q13). Our case and two other infantile cases reported by other investigators establish the novel association of the t(1;22) with AMKL.

Antibodies, Monoclonal↗

Cellular immunosuppression in children with acute lymphoblastic leukemia: effect of consolidation chemotherapy.

The present study was designed to evaluate the chemotherapy-induced cellular immunosuppression in 20 children with acute lymphoblastic leukemia (ALL) in remission and receiving maintenance chemotherapy. Peripheral blood was serially obtained from leukemic children during vincristine/cyclophosphamide/6-mercaptopurine/prednisone combined consolidation chemotherapy. The mean absolute number of peripheral blood lymphocytes as well as the mean absolute numbers of lymphocyte subsets (T cells, T cell subsets, B cells, and natural killer cells) from leukemic children before consolidation chemotherapy were all significantly lower than in control subjects; however, the percentages of lymphocyte subsets were similar in both groups. After consolidation chemotherapy, the percentages of CD4+ T lymphocytes and natural killer (NK) cells were significantly decreased and the percentages of monocytes and CD8+ T lymphocytes were significantly increased. Phytohemagglutinin- and 12-O-tetradecanoylphorbol-13-acetate-induced production of interleukin-2 (IL-2) and NK-cell-mediated cytotoxic activity by peripheral blood mononuclear cells (PBMC) were also substantially decreased in the post-therapy groups. NK activity correlated with the percentage of NK cells in PBMC. In contrast, OK432-induced production of tumor necrosis factor alpha (TNF alpha) and killer activity against NK-resistant target cells were significantly increased after therapy as compared with the pre-therapy and control groups. TNF alpha production correlated with the percentage of monocytes in PBMC. These results demonstrate that substantial quantitative and qualitative chemotherapy-induced abnormalities of the cellular immune system are present in the majority of patients treated with ALL. It is also suggested that the increased TNF alpha production by monocytes and the appearance of potent killing activity against NK-resistant targets might compensate for the defects of IL-2 production and NK activity during intensive consolidation chemotherapy.

Animals↗

Shedding of CD9 antigen by bone marrow cells from patients with acute lymphoblastic leukaemia.

The levels of soluble CD9 antigen released into spent medium from bone marrow (BM) cells were assayed using a unique enzyme-linked immunosorbent assay. We demonstrated that a considerable amount of soluble CD9 antigen was consistently detected in the spent medium from CD9+ leukaemic blasts, but little from normal or regenerating BM cells. The sensitivity and specificity of CD9 antigen assay were tested. First, BM cells taken from patients in complete morphologic remission (CR) were studied, and the distinct level of CD9 antigen was detected in 16.3% of the cases. Second, the outcome of leukaemic patients with significant shedding of CD9 antigen from BM cells while in CR was investigated: all patients have developed systemic relapse within 5-24 (median 15.4) weeks. In contrast, 24/34 patients without the increase of CD9 antigen levels are still in CR (follow-up 19-149 weeks, median 56.2 weeks). Only 10 patients in this group have relapsed so far. No false-positive results were detected with this sensitive assay for soluble CD9 antigen, and the introduction of appropriately planned prospective studies is justified on the basis of these observations.

Antigens, CD↗

Prediction of advanced puberty by height velocity in children with acute lymphoblastic leukemia.

Pubertal development was retrospectively evaluated in 58 children with cancer, mostly acute lymphoblastic leukemia (ALL), who are in complete remission and off chemotherapy. Six girls [5 patients with ALL, and 1 with malignant lymphoma (NHL)] showed advanced puberty (25.0%, 6 of 24 female patients with ALL and NHL) through the evaluation of their growth velocity. No evidence for advanced puberty was seen in the males. All 6 girls had received cranial irradiation for central nervous system prophylaxis and systemic chemotherapy including glucocorticoid. The mean age at onset of the pubertal growth spurt in these 6 girls was significantly lower than for girls with a solid tumor [6.90 +/- 0.10 and 9.00 +/- 0.77 (mean +/- SD) years, respectively (p < 0.01)]. By simply evaluating the height velocity, we could predict advanced puberty which was ultimately associated with short stature.

Adolescent↗

CD34 antigen expression in children with Philadelphia chromosome-positive acute lymphoblastic leukemia.

One characteristic of Philadelphia chromosome (Ph')-positive acute leukemia is the occasional presence of both lymphoid and myeloid features in the same leukemia. This phenomenon supports the theory that this subtype of acute leukemia arises from lymphoid-myeloid stem cell, pluripotent progenitors. Very few reports, however, describe the immunophenotype, especially CD34 antigen, of Ph'-positive acute lymphoblastic leukemia (ALL). It has been shown that CD34, the human progenitor cell antigen, is found on 1% or less of normal human bone marrow cells, approximately 30% of acute leukemias, and multipotent progenitor cells; CD34 is not found on normal peripheral blood cells. A high frequency of CD34 expression was found in children with Ph'-positive ALL: CD34 was positive for all six patients tested, and one had an acute mixed-lineage leukemia. These findings suggest the involvement of a pluripotent stem cell in Ph'-positive ALL.

Antigens, CD↗

Hyperimmunoglobulinemia D following cancer chemotherapy.

Five classes of serum immunoglobulin levels were investigated in 107 children with malignant or benign tumors. Hyperimmunoglobulinemia D (hyper-IgD) was observed in 31 of 82 children who were in complete remission off chemotherapy with a median follow-up of 4.5 years after cessation of chemotherapy. On the other hand, hyper-IgD was not found among 12 children with malignant or benign tumors treated with chemotherapy and a low incidence of hyper-IgD was observed during chemotherapy (1 of 13 cases). The result indicates that hyper-IgD is not uncommon in children off chemotherapy, suggesting that dysregulation of IgD synthesis persists long after cessation of antineoplastic drugs.

Adolescent↗

Shedding of CD9 antigen into cerebrospinal fluid by acute lymphoblastic leukemia cells.

The accurate identification of small numbers of leukemic cells in the cerebrospinal fluid (CSF) presents a diagnostic problem in the treatment of acute lymphoblastic leukemia (ALL). We demonstrated that soluble CD9 antigen was shed into CSF obtained from children with ALL, using enzyme-linked immunosorbent assay (ELISA), which used the activity of CD9 antigen to bind the Ricinus communis agglutinin (RCA1) and a monoclonal antibody, SJ-9A4, simultaneously. Using RCA1/SJ-9A4 ELISA, CD9 antigen was detectable in CSF but not in plasma from 12 cases of CD9+ ALL in central nervous system (CNS) relapse. However, CD9 antigen was not released into CSF from 11 cases of CD9- ALL with CNS involvement, 136 cases of CD9+ ALL in complete remission (CR), 29 cases of CD9- ALL in CR, or 21 cases of aseptic meningitis. Interestingly, the levels of CD9 antigen were elevated in CSF from 7 of 10 CD9+ ALL patients without cytologically proven CNS involvement at diagnosis, with subsequent return to undetectable levels after initial induction chemotherapy was begun. In addition, sequential analysis of CSF from a 5-year-old boy with CD9+ ALL in CNS relapse showed that levels of CD9 antigen correlated well with the number of leukemic cells in CSF. Serial quantitative analysis of CD9 antigen in CSF could be useful to detect the proliferation of residual leukemic cells before the clinical manifestation.

Antibody Specificity↗