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Biomedical subjects

Kazuhiro Ueda

Publications and source records attributed to Kazuhiro Ueda.

32 records · Page 2Linked to original sources

Obstacles for shortening hospitalization after video-assisted pulmonary resection for lung cancer.

BACKGROUND: Video-assisted thoracic surgery for lung cancer facilitates early postoperative recovery when patients are treated by critical pathway management. Thus, we developed an original programmed regimen for postoperative management, evaluated the validity of this regimen, and analyzed clinical factors influencing postoperative recovery. METHODS: Forty consecutive patients with suspicious lung cancer undergoing anatomic pulmonary resection with video-assisted thoracic surgery were enrolled in this prospective study. After surgery, all patients who underwent anatomic resection were managed using our programmed regimen; a patient was considered recovered when the regimen had been completed. RESULTS: On final pathologic examination, 37 cases were determined to have lung cancer and underwent anatomic resection. The mean number of resected segments was 3.6. There were no complications caused by postoperative management. The mean day of postoperative recovery was 3.7 days and median, 3 days. Significant preoperative factors related to recovery were age, breathlessness, performance status, radiologic emphysema, partial pressure of arterial oxygen, and predictive postoperative forced expiratory volume in 1 second. The overall number of these risk factors was specifically related to postoperative recovery (p < 0.01): the rate of recovery on postoperative day 3 was 100% in patients with no risk, 68% in those with one to three risks, and 22% in those with four to six risks. CONCLUSIONS: Our original regimen is useful as a critical pathway for the management of lung cancer patients undergoing video-assisted thoracic surgery. Furthermore, we created specific criteria to identify risk factors related to postoperative recovery that may be useful in planning hospitalization for patients undergoing video-assisted thoracic surgery.

Aged↗

Pharmacokinetics of etoposide with intravenous drug administration in children and adolescents.

BACKGROUND: Pharmacokinetics of etoposide in Japanese children and adolescents has not been investigated. The objectives of the present study were (i) to document the pharmacokinetics of etoposide in Japanese children; (ii) to determine the intra- and interpatient variability in systemic etoposide exposure and (iii) to obtain insights into the age-pharmacokinetic parameter relationship. METHODS: Pharmacokinetic studies of etoposide, given at doses of 60-200 mg/m2 by intravenous (i.v.) route of administration, were conducted in 18 children and adolescents (aged <19 years) with malignant diseases. High performance liquid chromatography was used to measure the blood etoposide levels. RESULTS: Pharmacokinetic parameters (mean~SD) of the 14 patients (24 courses) who received etoposide 100 mg/m2 were as follows: peak serum concentration (Cmax), 18.5~6.4 microg/mL; trough serum concentration, 0.2~0.1 microg/mL; biological half-life (T1/2), 3.6~0.7 h; volume of distribution (Vd), 6.3~3.4 L/m2; area under the etoposide serum concentration-time curve (AUC), 129~38 hr x microg/mL; systemic clearance, 21.1~10.8 mL/min per m2. The T1/2, Vd, and AUC were not associated with age. An increase in etoposide dose per body surface area (BSA) was associated with increase in its Cmax and area under the time-concentration curve (AUC). Wide interpatient variability in these parameters was demonstrated. CONCLUSIONS: The present study demonstrated that: (i) Pharmacokinetics of etoposide in Japanese children and adolescents were similar to those in Caucasians. (ii) Increased exposure to etoposide was associated with the Cmax. A clear correlation between Cmax and AUC was also found. (iii) Selecting the dose of etoposide according to body surface area (BSA) might give an acceptable range of exposure for children more than 1 year of age.

Adolescent↗

Polyclonal proliferation of lymphocytes containing the epstein-barr virus genome in a patient dying of myocarditis in chronic active Epstein-Barr virus infection.

An 11-year-old boy had intermittent fever and hepatosplenomegaly. The diagnosis of chronic active Epstein-Barr virus (EBV) infection was established from an abnormal pattern of anti-EBV antibody; EBV was detected in bone marrow cells. Immunochemotherapy alleviated the patient's symptoms. However, when a subsequent oral prednisolone dose was tapered, heart failure ensued and he died. Autopsy findings demonstrated that myocarditis resulted from infiltrating T lymphocytes with the EBV genome and a benign histologic appearance. A clonality study of T lymphocytes indicated no such evidence of monoclonality. EBV-infected T cells play an important role in the pathogenesis of myocarditis in chronic active EBV infection.

Antineoplastic Agents, Hormonal↗

Efficacy of prophylactic use of trimethoprim-sulfamethoxazole in autoimmune neutropenia in infancy.

PURPOSE: Most children with autoimmune neutropenia (AIN) have a benign clinical course because of the spontaneous resolution of neutropenia. The authors observed the clinical course of AIN in infancy accompanied by the prophylactic use of trimethoprim-sulfamethoxazole (TMP-SMX) during neutropenia. PATIENTS AND METHODS: Eight infants with AIN were followed by serial tests for antineutrophil antibodies and management of infectious complications. RESULTS: The spontaneous disappearance of antineutrophil antibodies that preceded the normalization of the neutrophil count was found in all patients. Until the resolution of neutropenia, TMP-SMX was administered in five patients, resulting in a reduction in the incidence of infection with no adverse effects. CONCLUSIONS: These observations demonstrate the possibility of the safety and usefulness of TMP-SMX treatment in patients with AIN.

Anti-Infective Agents↗

Dysregulation of transcriptions in primary granule constituents during myeloid proliferation and differentiation in patients with severe congenital neutropenia.

We examined the expression of granule constituent genes in myeloid progenitor cells during proliferation and differentiation in patients with severe congenital neutropenia (SCN). The heterozygous mutation of the neutrophil elastase gene was identified in two of four patients. The CD34+/granulocyte-colony stimulating factor receptor (G-CSFR)+ cells of SCN patients showed defective responsiveness to G-CSF in serum-deprived culture. The CD34+/G-CSFR+ cells expressed low levels of the granule constituent mRNAs. The transcription levels of primary granule enzyme genes in CD34+/G-CSFR+ cells were gradually enhanced and then decreased when cells were induced toward myeloid lineage with G-CSF in normal subjects. However, the primary up-regulation and the following down-regulation of these enzyme transcriptions were not clearly observed in SCN patients. No differences in expressions of the lactoferrin gene were seen between normal subjects and patients with SCN. We hypothesize that the abnormal regulation of the transcription in primary granule constituents might involve the defective proliferation and differentiation of myeloid cells in patients with SCN.

Bone Marrow Cells↗

Determination of etoposide serum concentrations in small pediatric samples by an improved method of reversed-phase high-performance liquid chromatography.

Several specific assays have been developed for the measurement of etoposide in biological fluids. As large samples are required for high sensitivity, these systems are not appropriate for a pediatric practice. In the present study, however, an improved method for the determination of serum levels of the anticancer drug etoposide was developed, using high-performance liquid chromatography with fixed-wavelength ultraviolet detection. Etoposide was extracted from serum using dichloromethane. The efficiency of extraction from serum was 85.7 +/- 7.7% for etoposide and 81.1 +/- 8.4% for diphenylhydantoin, the internal standard. The serum concentrations of etoposide were measured in 0.2-ml serum samples. The lower limit of detection was 50 ng/ml. Each measurement was completed within 5 min. The linear quantitation range for etoposide was 0.05-50 microg/ml. This assay presents an alternative method for routine measurement of serum levels of etoposide in the pediatric oncology setting.

Antineoplastic Agents, Phytogenic↗

Significance of the detection of antineutrophil antibodies in children with chronic neutropenia.

We evaluated the clinical characteristics of 41 children with chronic neutropenia based on the quantitative analysis of antineutrophil antibodies in serum by flow cytometry. According to the strength of antineutrophil antibodies, the patients were divided into 3 groups: 12 patients presented negative antibodies, 13 patients showed weak positive antibodies, and 16 patients showed strong positive antibodies. No significant differences were seen in age of diagnosis, severity of neutropenia, and infectious complications associated with neutropenia among the 3 groups. The spontaneous resolution of neutropenia was observed in all patients with negative antibodies and in 22 of 29 patients with positive antibodies. The age of the recovery of neutropenia and the duration until spontaneous resolution of neutropenia were significantly dependent on the antibody strength at the time of diagnosis. These results demonstrate that the quantification of antineutrophil antibodies at the time of diagnosis may be useful in considering the clinical course of chronic neutropenia in childhood.

Agglutination Tests↗

Outcome after relapse in childhood acute lymphoblastic leukemia.

Among 157 children with acute lymphoblastic leukemia (ALL) who experienced relapse at 54 institutes participating in the Japan Association of Childhood Leukemia Study, we analyzed the outcomes after relapse in 103 and 30 eligible cases with bone marrow (BM) and central nervous system (CNS) relapse, respectively. Reinduction rates in BM and CNS relapse cases were 72.3% and 83.3%, respectively. High reinduction rates were observed in B-precursor (B-pre) phenotype ALL in both relapse groups and in late (more than 24 months from onset) BM-relapse patients. After BM relapse, the overall 5-year survival rate was superior in the allogeneic stem cell transplantation (SCT) group compared to the non-SCT group (41.9%+/-8.2% versus 13.6%+/-6.5%, P < .0001). In contrast, the 4-year overall survival rate was not significantly different between the SCT (allogeneic plus autologous) and non-SCT groups after CNS relapse (26.8%+/-14.2% versus 61.9%+/-12.3%, P = .252). The late BM-relapse patients showed a significantly higher survival rate than did early-relapse patients, and survival rates were similar between the allogeneic and autologous group when the patients underwent SCT during a second complete remission. Moreover, B-pre ALL patients classified in the standard-risk group according to National Cancer Institute/Rome's criteria at onset had a good prognosis after allogeneic SCT. Improving the cure rate in relapsed ALL patients requires more intensive reinduction therapy and efforts to succeed with SCT in early BM-relapse patients as well as the establishment of a treatment strategy including indications of SCT for CNS-relapse patients.

Child↗

Hilar lymph nodes in N2 disease: survival analysis of patients with non-small cell lung cancers and regional lymph node metastasis.

PURPOSE: This study was conducted to accurately define the N status of non-small cell lung carcinoma (NSCLC). METHODS: We retrospectively reviewed 147 patients with NSCLC and pathologically positive regional lymph nodes who underwent major pulmonary resections with complete mediastinal lymph node dissections. RESULTS: The overall 5-year survival rate was 41% after a median follow-up period of 33 months. The survival rate of patients with hilar N1 disease (26%) was significantly lower (P = 0.002) than that of those with interlobar and intrapulmonary N1 disease (60%). The survival rate of patients with hilar N1 disease (26%) was similar to that of those with N2 disease (33%; P = 0.56). Cox proportional hazards analysis with the covariates of age, sex, cell type, site of resection, pathological T factor, and pathological N factor revealed that pathological N factor indicated a relative risk for N2 disease of 1.76 (P = 0.028). Grouping hilar N1 disease with N2 disease showed that the relative risk of this "new N2 disease" with the same covariates was 2.65 (P = 0.002). CONCLUSION: According to our data, hilar N1 disease should be grouped with N2 disease because this combined category accurately reflects surgical outcome.

Adult↗

Diclofenac (Voltaren)-induced pneumonitis after chest operation.

We report a rare case of nonsteroidal anti-inflammatory drug-induced pneumonitis in a 72-year-old man taking diclofenac for wound pain after pulmonary resection. The pneumonitis and pleural effusion were predominant on the operative side and resolved rapidly after the diclofenac was discontinued. The diagnosis of drug-induced pneumonitis was based on a lymphocyte stimulation test that was positive for diclofenac sodium and negative for other drugs. This case report demonstrated that surgeons should be aware of the possibility of pneumonitis induced by a nonsteroidal anti-inflammatory drug.

Aged↗

High-dose chemotherapy in children with metastatic hepatoblastoma.

BACKGROUND: Despite the advent of effective chemotherapy,a poor prognosis has been reported for patients with metastatic hepatoblastoma. To improve this prognosis, we conducted high-dose chemotherapy with autologous bone marrow rescue in patients with metastatic hepatoblastoma. METHODS AND RESULTS: Three patients were treated with high-dose chemotherapy. In patient 1, high-dose chemotherapy was given after the patient's first pulmonary relapse. Additional pulmonary metastases, which developed more than 6 months after high-dose chemotherapy, were treated by multiple thoracotomy without additional chemotherapy. Patient 2 presented additional pulmonary metastases soon after the end of the first thoracotomy and high-dose chemotherapy. Because of a decreased serum alpha-fetoprotein level after re-excision of the pulmonary metastases, a second round of high-dose chemotherapy was performed. In patient 3, multiple pulmonary metasteses responded to preoperative chemotherapy and disappeared according to the chest computed tomography. Intensive treatment with a high-dose chemotherapeutic regimen was performed at the end of postoperative chemotherapy. All three patients are alive and well, more than 6 years after receiving their diagnosis. CONCLUSION: The role of high-dose chemotherapy in treatment of metastatic hepatoblastoma could not be clarified,because of the small number of patients. However, the better outcome of our patients indicates that multimodal therapy, including high-dose chemotherapy, may improve the outcome of the patients with metastatic hepatoblastoma.

Antineoplastic Combined Chemotherapy Protocols↗

Low plasma levels of hemostatic proteins during the induction phase in children with acute lymphoblastic leukemia: A retrospective study by the JACLS. Japan Association of Childhood Leukemia Study.

BACKGROUND: Thromboembolic and bleeding events are serious complications associated with the administration of L-asparaginase (ASP) during the induction phase in children with acute lymphoblastic leukemia (ALL). Prophylactic supplementation of plasma-derived coagulation products remains controversial. The purposes of this study were to examine the plasma levels of hemostatic proteins during the induction phase and the efficacy of prophylactic replacement of plasma-derived products. METHODS: A multicenter retrospective survey on the incidence of hemostatic complications and the frequency of prophylactic replacement of plasma-derived products among children with ALL who under went ASP therapy was conducted. All patients were treated according to the Japan Association of Childhood Leukemia Study (JACLS) ALL-97 protocol. RESULTS: Thirty-six (67%) of the 54 JACLS-treatment centers responded and provided information on 127 patients. Clinically relevant hemostatic complications occurred in two patients (1.6%;2/127); one patient suffered intracranial bleeding 5 days after beginning the protocol, and the second patient suffered an ischemic attack during an ASP treatment. The administration of ASP(10 000 u/m2 x six doses) led to significant reductions in the plasma fibrinogen (180 +/- 74 to 105 +/- 57 mg/dL),antithrombin III (AT III) (126 +/- 21 to 73 +/- 18%),and plasminogen levels (97 +/- 17 to 52 +/- 18%). These laboratory parameters returned to normal levels 2 weeks after completion of the ASP treatment. Forty-eight patients (38%)received AT III concentrate (AT III-supplement group). The AT III level of the AT III-supplement group was significantly lower than that of the AT III non-supplement group, not only during the ASP therapy, but also prior to the ASP therapy. A greater percentage of patients in the AT III-supplement group received fresh-frozen plasma and in greater amounts than those in the AT III non-supplement group. CONCLUSIONS: Severe hemorrhage and thrombosis were uncommon in the ALL patients who underwent ASP therapy in comparison with the degree of coagulation changes. Prophylactic administration of AT III concentrate or fresh-frozen plasma did not demonstrate clear beneficial effects in the treatment of ALL in preventing thromboembolic events.

Antineoplastic Agents↗

Defects of granulopoiesis in patients with severe congenital neutropenia.

To confirm the abnormalities of primitive myeloid progenitor cells in patients with severe congenital neutropenia (SCN), we studied their responsiveness to hematopoietic factors including granulocyte colony-stimulating factor (G-CSF). In all SCN patients studied no abnormalities of granulocyte colony-stimulating factor receptor (G-CSFR) gene were detected by polymerase chain reaction-single-strand conformation polymorphism analysis and sequence analysis. A flow cytometric analysis of bone marrow cells based on the expression of CD34, Kit receptor, and G-CSFR demonstrated a reduced frequency of CD34+/Kit+/G-CSFR+ cells in patients with SCN. The granulocyte/macrophage (GM)-colony formation of CD34+/Kit+/G-CSFR+ cells in patients was markedly decreased at all concentrations of G-CSF in serum-deprived semisolid culture. The responsiveness of CD34+/Kit+/G-CSFR+ cells in patients showed a reduced response to the combination of stem cell factor, the ligand for flk2/flt3, and interleukin-3 with or without G-CSF in serum-deprived semisolid and liquid suspension cultures. In contrast, no difference in the responsiveness of CD34+/Kit+/G-CSFR- cells was noted between SCN patients and normal subjects. The bone marrow cells from a patient who underwent bone marrow transplantation showed a restoration of both the reduced frequency and the decreased level of GM-colony formation of CD34+/Kit+/G-CSFR+ cells. These results demonstrate that the presence of qualitative and quantitative abnormalities of primitive myeloid progenitor cells expressing G-CSFR may play an important role in the impairment of granulopoiesis in patients with SCN.

Antigens, CD34↗