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Biomedical subjects

Takahiro Okamoto

Publications and source records attributed to Takahiro Okamoto.

17 recordsLinked to original sources

Measuring quality of life in patients with breast cancer: a systematic review of reliable and valid instruments available in Japan.

BACKGROUND: Little is known about the availability and psychometric properties of instruments to measure quality of life (QOL) in clinical research on Japanese patients with breast cancer. The purpose of this systematic review is to find reliable and valid instruments available in Japan, and to summarize their characteristics. METHODS: Instruments available in Japan were found through a systematic search of the literature. Each instrument identified was evaluated for item development, reliability, validity, interpretability and utility. RESULTS: Six questionnaires to measure health-related QOL (the QOL-ACD, the EORTC QLQ-C30, the EORTC QLQ-BR23, the FACT-B, the SF-36, the WHO/QOL-26) and five scales to quantify the psychological burden (the STAI, the POMS, the SDS, the HADS, the GHQ), for which reliability and validity have been documented, are available in Japanese. All instruments were developed in foreign countries except for the QOL-ACD. Two of the QOL questionnaires were specific to breast cancer (the EORTC QLQ-BR23, the FACT-B). Though the measurements can be interpreted in some manner, the meaning of change scores over time has been documented for only three instruments (the EORTC QLQ-C30, the FACT-B, and the GHQ). CONCLUSIONS: The review provides grounds for designing and implementing quantitative research on QOL of breast cancer patients in Japan. Methodological challenges, however, continue, particularly for validating instruments with regard to various study populations of Japanese people and demonstrating the clinical importance of change scores.

Breast Neoplasms↗

Cyclosporin A therapy for patients with myelodysplastic syndrome: multicenter pilot studies in Japan.

We examined the efficacy of cyclosporin A (CsA) in 50 patients with myelodysplastic syndrome (MDS) consisting from 47 of RA, 1 of RARS, and 2 of RAEB. These patients showed various marrow cell types including hypo-, normo-, and hypercellularity. Patients belonged to the following International Prognostic Scoring System (IPSS) risk groups: 4 of low, 41 of intermediate-1, and 5 of intermediate-2. The median CsA dose was 4.58mg/kg, and treatment responses were classified according to the International Working Group (IWG) criteria. Hematological improvement (HI) was observed in 30 (60%) patients, and all of them were belonged to RA. In the patients with RARS or RAEB, no efficacy was observed. Four (8%) of the responders achieved partial remission (PR) with granulocytes > or = 1500microl(-1), Hb>11g/dl and platelets > or = 100,000microl(-1). Higher response rate (53%) was shown in erythroid lineage (HI-E) compared to platelet (HI-P, 36%) or neutrophil lineage (HI-N, 35%). When we analyzed the correlation between the response to CsA therapy and the karyotype or HLA type, there were significantly more responders with good karyotype or DRB1*1501 than with intermediate/poor karyotypes or with other HLA types. These results indicate the usefulness of CsA therapy for MDS patients with any marrow cellularity, especially for erythroid lineage and patients with good karyotype or DRB1*1501.

Adolescent↗

Idiopathic interstitial pneumonia following stem cell transplantation.

Idiopathic interstitial pneumonia (IIP) can occur after stem cell transplantation, but the aetiology is unknown. Based on the association between angiitis syndrome and Helicobacter pylori infection, we identified possible risk factors common to these two conditions. Among 83 patients who underwent stem cell transplantation, four developed IIP. We elucidated various parameters and clinical features in four patients with IIP and 79 patients without, after allogeneic stem cell transplantation. In all four patients, (1) the conditioning regimen induced total body irradiation, (2) serological reactivation of cytomegalovirus and/or human herpesvirus-6 preceded the onset of IIP, (3) their human leucocyte antigen types were among those suspected to increase susceptibility to angiitis syndrome, (4) serum anti-H. pylori antibody was positive before conditioning and remained positive throughout the post-transplantation course, (5) inflammatory cytokines (interleukin-6, 8 and 12) were increased during the period of leucocyte recovery after transplantation and (6) the levels of intercellular adhesion molecule-1, thrombomodulin and plasminogen activator inhibitor-1 were increased at the onset of IIP. These findings suggest the possibility that angiitis syndrome and H. pylori infection are involved in the pathogenesis of post-transplantation IIP.

Adult↗

Intestinal graft-versus-host disease: mechanisms and management.

Allogeneic haematopoietic stem cell transplantation remains the treatment of choice for a number of malignancies. However, graft-versus-host disease (GVHD) has long been regarded as a serious complication of this procedure. Although GVHD may affect any organ, intestinal GVHD is particularly important because of its frequency, severity and impact on the general condition of the patient. Recent studies have led to progressive elucidation of the mechanism of GVHD. Donor T cells are critical for the induction of GVHD, because depletion of T cells from bone marrow grafts effectively prevents GVHD but also results in an increase of leukaemia relapse. It has been shown that the gastrointestinal tract plays a major role in the amplification of systemic disease because gastrointestinal damage increases the translocation of endotoxins, which promotes further inflammation and additional gastrointestinal damage. Consequently, the management of intestinal GVHD (and the intestine itself) is a subject that should be highlighted. In this article, approaches to the prevention of intestinal GVHD are discussed after being classified into three categories: regimens in common clinical use, regimens under investigation and original regimens used at our hospital. The standard regimen that is used most widely for prevention of GVHD is cyclosporin plus short-term methotrexate. Corticosteroids can be added to this regimen but careful consideration of the adverse effects of these hormones should be considered. Tacrolimus is a newer, more potent alternative to cyclosporin. T-cell depletion (TCD) after transplantation has been shown to prevent acute GVHD, however, the survival benefit of TCD has not been as great as expected. Mycophenolate mofetil can be useful for the treatment of acute GVHD as part of combination therapy. Regimens currently under investigation in animal experiments include suppression of inflammatory cytokines and inhibition of T-cell activation, and, specifically at our institution, hepatocyte growth factor gene therapy. The evidence-based therapy used at our institution includes systemic antibacterial therapy (including eradication of intestinal bacteria) to prevent the intestinal translocation of lipopolysaccharide and avoid the subsequent increase of various inflammatory cytokines. In addition, because of the similarities between intestinal GVHD and ulcerative colitis, sulfasalazine, betamethasone enemas and eicosapentaenoic acid have been used to treat intestinal GVHD in some patients.

Adrenal Cortex Hormones↗

In vitro transfer of antisense oligodeoxynucleotides into coronary endothelial cells by ultrasound.

Since antisense oligodeoxynucleotides (AS-ODNs) have been recognized as a new generation of putative therapeutic agents, we established a delivery technique that could transfect AS-ODNs, which are designed for endothelin type B receptor (ETB), into cultured human coronary endothelial cells (HCECs) by exposure to ultrasound in the presence of echo contrast microbubbles. Ultrasound offers several advantages such as being nontoxic, nonantigenic and providing rapid gene transfer. We standardized the optimal conditions, which consisted of 2 x 10(6) cells suspended in phosphate buffer with 900nM ODN, 50 microl of echo contrast microbubbles (Optison), and ultrasound exposure (1.0 W/cm(2), 10% duty cycle, and 10s duration). The percentage of transfected cells was 25.2+/-2.0% after ultrasound treatment. This is the first demonstration of the use of the ultrasound exposure technique in conjunction with microbubbles in HCECs.

Base Sequence↗

Outcome study of psychological distress and nonspecific symptoms in patients with mild primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism is a common endocrinopathy. The appropriate management of its mild form, however, remains controversial. HYPOTHESIS: Mild primary hyperparathyroidism is associated with psychological distress and other nonspecific symptoms that improve following parathyroidectomy. DESIGN: Two-year prospective before-after study. SETTING: University hospital. PATIENTS: Twenty-six consecutive patients with mild hypercalcemia (<12 mg/dL [<3 mmol/L]) due to primary hyperparathyroidism, without osteitis fibrosa cystica or urolithiasis were enrolled from January 11, 1997, through April 21, 1998. INTERVENTION: Parathyroidectomy. MAIN OUTCOME MEASURES: Primary outcome was psychological distress as measured by the 28-item version of the General Health Questionnaire. Secondary outcomes included body weight, joint pain, and occurrences of bowel movements and urination. RESULTS: Before surgery, 15 patients (58%; 95% confidence interval, 37%-77%) showed psychological distress (case group) while 11 patients did not (noncase group). A clinically and statistically significant reduction in the General Health Questionnaire score was detected at 3 months in the case group (-6.1; 95% confidence interval, -11.0 to -1.2), but the reduction was smaller (-1.9; 95% confidence interval, -6.9 to 3.0) at 24 months after surgery. No significant change in the General Health Questionnaire score was observed in the noncase group during the follow-up. No significant change was noted in any of the secondary outcomes. CONCLUSIONS: Psychological distress was associated with mild primary hyperparathyroidism and was ameliorated after surgery. The improvement, however, was limited in extent and duration.

Aged↗

Systematic overview of quality of life studies for breast cancer.

BACKGROUND: The concept of quality of life (QOL) is essentially subjective, determined from the patient's point of view. Thus, an appropriate investigation and analysis of QOL as an indicator of medical treatment outcome is a task of some difficulty. The physician-led QOL assessment studies to date in Japan have suffered from insufficient knowledge and understanding of the diverse factors contributing to QOL, thereby contributing to a dearth of quality studies. Given this background, the Japanese Breast Cancer Society has established a Task Force for the development of guidelines to properly conduct QOL assessment studies. The present article reports the results of a large-scale systematic overview of QOL assessment studies for breast cancer patients that was undertaken as one part of this project. METHODS: Six databases were used in this overview: MEDLINE, CINAHL, CANCERLIT, EMBASE, PsychINFO, and Japan Centra Revuo Medicina. The search period was 1982-1999 for CINAHL, and 1990-1999 for the others. Following a check of the titles, important information was recorded on relevance and data collection forms. RESULTS: A systematic search was conducted of the literature on QOL assessment studies for breast cancer patients, and 1,954 articles were extracted from a check of titles. Using the relevance and data collection forms, the number of articles was further narrowed to 126. These articles were then classified according to the type and design of the study, the number of QOL and psychological measures used, frequency of use of each measure, and study focus and type of intervention. The results were then compiled. CONCLUSION: To date there have been almost no appropriate systematic overviews or guidelines issued for QOL assessment studies related to breast cancer, even on the international level. The results of the present study may contribute high-quality QOL information for evidence-based medicine, as it continues to gain global prevalence.

Adaptation, Physiological↗

Expression of the antiapoptosis gene survivin in human leukemia.

Loss of the inhibition of apoptosis is important in leukemogenesis and may influence the prognosis. Survivin is an inhibitor of apoptosis that shows selective expression during fetal development and in human malignancies. Survivin expression was examined in human leukemias using the reverse transcriptase-polymerase chain reaction. Survivin gene expression was detected in 17 of 31 patients with acute myelocytic leukemia and 11 of 16 patients with acute lymphocytic leukemia but was not identified in normal bone marrow cells. Survivin expression was lower in patients with M3 acute myelocytic leukemia than in patients with other types of acute leukemia. Survivin was not detected in the chronic phase of chronic myelocytic leukemia but was observed in 5 of 7 patients with chronic myelocytic leukemia in blastic crisis. These findings suggest a relationship between survivin gene expression and hematopoietic cell differentiation. In fact, survivin gene expression was down-regulated during the differentiation of HL-60 cells after treatment with dimethyl sulfoxide or all-trans-retinoic acid. Moreover, the disease-free survival rates of patients with survivin expression were lower than in patients without survivin expression. Accordingly, survivin may have a role in leukemogenesis as well as in other malignancies. Detecting survivin may also provide prognostic information.

Acute Disease↗

Effects of total body irradiation on the vascular endothelium.

Total body irradiation (TBI) is used as conditioning for stem cell transplantation. We studied its effects on the vascular endothelium in 55 consecutive patients undergoing stem cell transplantation with TBI (TBI group n=35) or without TBI (non-TBI group: n=20). Fifty patients underwent bone marrow transplantation and five underwent peripheral blood stem cell transplantation. The levels of thrombomodulin, plasminogen activator inhibitor-1, and cyclic GMP were measured before and after TBI. At both times, the thrombomodulin and plasminogen activator inhibitor-1 levels were within the normal range in all patients from the two groups, without any significant differences between the groups. The cyclic GMP level was increased after TBI in six of 35 patients. Five of these six patients died as a result of complications of transplantation, while one patient survived in whom the cyclic GMP level rapidly returned to normal. In contrast, the cyclic GMP level remained normal in all patients not receiving TBI. These results suggest that conditioning with TBI stimulates vascular endothelial cells, even if it does not cause immediate direct injury. Such stimulation may be related to vascular endothelial dysfunction, the development of which may be mediated by nitric oxide.

Adolescent↗

Similarity between hepatic graft-versus-host disease and primary biliary cirrhosis.

Similarities between hepatic graft-versus-host disease (GVHD) and primary biliary cirrhosis (PBC) have been reported recently. To examine this association, we studied 60 patients who underwent allogeneic bone marrow transplantation (BMT) consecutively at a single medical institution.Among the 60 patients, 12 developed hepatic GVHD after BMT and 48 did not. These two groups were compared with respect to various characteristics seen in PBC, such as autoantibodies, human leukocyte antigen (HLA) status, infection and inflammatory cytokines. The two groups showed a significant difference in HLA DR status. There was also a significant difference in the febrile period and in cytokine levels between the patients with hepatic GVHD and 12 other patients who had no complications after transplantation. These findings suggest that hepatic GVHD resembles PBC and that HLA DR features of PBC may also be risk factors for the onset of hepatic GVHD.

Adult↗

Increased expression of interleukin-18 receptor on T lymphocytes in patients with acute graft-versus-host disease after allogeneic bone marrow transplantation.

Acute graft-versus-host disease (aGVHD), a potentially fatal side effect of allogeneic bone marrow transplantation (BMT), is initiated by the action of donor-derived T lymphocytes. We have shown previously that aGVHD is associated with elevated serum levels of interleukin-18 (IL-18). In this study, we analyzed the expression of the IL-18 receptor (IL-18R) on T lymphocytes of BMT patients with aGVHD. Flow cytometric analysis showed that in healthy subjects, a small population of CD4+ T cells expressed IL-18Ralpha, whereas a relatively large population of CD8+ T cells expressed IL-18Ralpha. In aGVHD patients, there were marked increases in the proportion of CD4+ or CD8+ T cells that express IL-18Ralpha. RT-PCR assays showed elevation of IL-18Ralpha and IL-18Rbeta mRNA levels in CD8+ T cells in aGVHD patients. These findings suggest that the expression of IL-18R is upregulated in T cells in patients with aGVHD and that the IL-18/IL-18R system is active during aGVHD.

Acute Disease↗

[Pneumonitis with a bronchiolitis obliterans organizing pneumonia-like shadow in a patient with human herpes virus-6 viremia after allogeneic bone marrow transplantation].

We report the case of a 42-year-old male who underwent allogeneic bone marrow transplantation (BMT) for acute myelogenous leukemia, and then developed pneumonitis with a bronchiolitis obliterans organizing pneumonia (BOOP)-like shadow. When he came with exertional dyspnea four months after BMT, the chest X-ray and CT findings disclosed bilateral infiltration, and remarkable elevation of his serum KL-6 level, a monitoring marker for disease activity in interstitial lung disease. Although organizing pneumonia (OP) was revealed by a transbronchial lung biopsy, no pathogen was detected in bacterial, fungal and routine viral cultures or by direct cytological examinations using bronchoalveolar lavage (BAL) specimens. Since human herpes virus-6 (HHV-6) was detected in BAL specimens by the polymerase chain reaction (PCR), a diagnosis of a pneumonitis-like BOOP shadow related to HHV-6 was made, and he was treated with methylprednisolone and ganciclovir (GCV). Although there was a relapse of his OP 1.5 months later, with re-elevation of his serum KL-6 level, continuous administration of GCV led to disappearance of HHV-6 in BAL specimens assayed by PCR, in association with normalization of the serum KL-6 level. HHV-6 should be considered as a cause of unexplained pneumonitis in BMT recipients, and KL-6 is useful for monitoring the pneumonitis status in these patients.

Adult↗

Common features in the onset of ARDS after administration of granulocyte colony-stimulating factor.

STUDY OBJECTIVE: Respiratory disturbance caused by ARDS has been reported during administration of granulocyte-colony stimulating factor. The clinical features of such respiratory distress were investigated in this study. DESIGN: Retrospective case review. SETTING: A 1,100-bed university teaching hospital. PATIENTS: Five patients who had dyspnea caused by ARDS develop after chemotherapy or bone marrow transplantation (BMT) at our hospital. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Levels of cytokines, human leukocyte antigen (HLA) typing, and the clinical course were analyzed to clarify common features. All five patients possessed HLA-B51 or HLA-B52, and all had fever and an enhanced inflammatory response at the time of the WBC nadir. The tumor necrosis factor (TNF)-alpha and interleukin (IL)-8 levels increased when respiratory distress syndrome occurred. CONCLUSIONS: If patients with HLA-B51 or HLA-B52 have infection develop at the time of WBC nadir after chemotherapy or BMT, ARDS may occur in association with elevation of TNF-alpha and IL-8 during WBC recovery.

Adult↗