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Biomedical subjects

Y Onozawa

Publications and source records attributed to Y Onozawa.

At least 19 recordsLinked to original sources

Invasive infection due to Trichosporon cutaneum in patients with hematologic malignancies.

BACKGROUND: Invasive infection due to Trichosporon is a rare but often fatal disease in immunocompromised patients. In this study, data on patients with hematologic malignancies who had an invasive infection due to Trichosporon diagnosed at the Tokyo Metropolitan Komagome Hospital in Tokyo, Japan, were analyzed. METHODS: Positive blood cultures obtained between 1986 and 1996 were reviewed. Medical records of all patients who were positive for Trichosporon in their blood culture or autopsy material were then examined. RESULTS: A total of nine patients with hematologic malignancies were reported positive for Trichosporon cutaneum in their blood culture or at the time of autopsy. The average age was 52 years, and all patients except 2 had acute leukemia. All 8 patients with positive blood cultures were neutropenic, and the average duration of neutropenia before the positive blood cultures were obtained was 43 (range, 0-101) days. For prophylaxis of fungal infection, eight patients were kept in a laminar air flow room and also received nebulization with amphotericin B. Five patients received oral amphotericin B. All 9 patients died of the infection an average of 9 days after their blood cultures turned positive. Minimal inhibitory concentrations were evaluated in six available strains obtained from the patients. They were all resistant to amphotericin B and azoles. CONCLUSIONS: More effective antifungal agents are required for the treatment of infections with this organism.

Adult

Response-oriented individualized induction therapy followed by intensive consolidation and maintenance for adult patients with acute lymphoblastic leukemia: the ALL-87 study of the Japan Adult Leukemia Study Group (JALSG).

The Japan Adult Leukemia Study Group conducted the ALL-87 study to determine whether response-oriented induction therapy and intensive consolidation and maintenance/intensification therapies could increase complete remission (CR) rate and survival in adult acute lymphoblastic leukemia (ALL). Of 121 patients registered, 116 were evaluated. Patients' ages ranged from 15 to 72 years (median, 38 years). Induction therapy, which consisted of doxorubicin, vincristine, cyclophosphamide, L-asparaginase and prednisolone, was given in a response-oriented individualized fashion. Patients were randomly allocated either to receive or not, intrathecal chemotherapy on day 8 of the induction therapy. Complete remission (CR) was obtained in 97 (83.6%) patients (90.2%) in patients of less than 50 years of age and 67.6% in patients 50 years of age or older). At a median follow-up period of 65 months, the predicted 6-year overall survival and event free survival (EFS) rates of 116 patients were 23.4 and 20.0%, respectively. Predicted 6-year survival and disease-free survival (DFS) rates of 97 CR patients were 28.2 and 24.5%, respectively. By multivariate analysis, patients under 40 years of age (P = 0.002) or those with a platelet count of more than 100,000/microliters (P = 0.004) were significant favorable prognostic factors for obtaining CR, and days to CR less than 50 (P = 0.003), patients under 50 years of age (P = 0.005) were significant favorable factors for longer DFS. There was no significant difference in CR rates and DFS between the two randomized groups according to the intrathecal chemotherapy on day 8. Response-oriented induction therapy produced a high CR rate, but fairly intensive consolidation and maintenance/intensification chemotherapies resulted in only a marginal effect on DFS in adult ALL. Although age is one of the most important prognostic factors in ALL, the outcome was unsatisfactory even in younger adult patients using chemotherapeutic regimen employed in this study.

Adolescent

Incidence and influence of GB virus C and hepatitis C virus infection in patients undergoing bone marrow transplantation.

Markers of GB virus C (GBV-C) and hepatitis C virus (HCV) were sought in 80 patients before and after they underwent BMT in a metropolitan hospital in Tokyo between 1990 and 1996. RNA of GBV-C was detected in 14 (18%) patients before BMT. Of the 55 patients who had been transfused, 14 (25%) possessed GBV-C RNA at a frequency significantly higher than in the 25 untransfused patients who were all negative (P < 0.01). HCV RNA was detected in three of the 55 (5%) transfused patients, but in none of the 25 untransfused patients. Sera at 3 months after BMT were available for 57 patients. GBV-C RNA persisted in all 10 patients who were infected before BMT, while it was detected in five of the remaining 47 (11%) patients who were not. However, persistent and/or ongoing GBV-C infection had no appreciable influence on patient morbidity or mortality. Two of the 57 patients were positive for HCV RNA before BMT and this persisted after BMT in both. HCV RNA became positive in eight of the remaining 55 (15%) patients who were negative before BMT. Of the 14 patients who received transfusions screened by the first-generation test at BMT, seven (50%) became positive for HCV RNA, a rate significantly higher than the one of 41 (2%) patients who received transfusions screened by the second-generation test (P < 0.001). These results indicate that BMT patients are at increased risk of GBV-C infection transmitted by transfusions received before and at the time of BMT, and that the risk of HCV infection has decreased after the implementation of the second-generation anti-HCV test.

Adolescent

Utility and safety of Hickman catheters for venous access after bone marrow transplantation.

Hickman catheters are useful for vascular access after bone marrow transportation because they can handle large volume and allow for easy transfusions and blood drawing through wide double lumens making it easier to case for patients under sterile conditions in a clean room. However, the safety of Hickman catheters as compared to Silastic catheters in marrow transplants has never been discussed. We therefore retrospectively reviewed the complications of two catheters in 71 allogeneic bone marrow transplant recipients between September 1986 and August 1994. The complication and infection rates of Hickman catheters were 0.21 and 0.09 per 100 device-life days, and rate of temperature >38 degrees C during leukocytopenia (<1,000 white blood cells) was 0.18. These rates were not different from those of Silastic catheters suggesting that Hickman catheters are safe and acceptable in marrow transplantation. The benefits and drawbacks of Hickman catheters relevant to catheter choice were also discussed.

Adolescent

[Hemolytic uremic syndrome after bone marrow transplantation].

One hundred and thirteen patients who underwent autologous or allogeneic bone marrow transplantation (BMT) were investigated for the subsequent development of hemolytic uremic syndrome (HUS). HUS developed in seven patients (four males and three females, five acute lymphocytic leukemia (ALL), one acute myelogenous leukemia, one non-Hodgkin's lymphoma) between 36-196 days after BMT. Four patients were recipients of autologous BMT and three were those of allogeneic BMT. Six patients were preconditioned with the regimens including fractionated total body irradiation (TBI). ALL and preconditioning regimen with TBI were suspected to be the risk factors for the development of HUS. Cyclosporin A (CSP) administration was discontinued in three patients who had been given CSP for graft-versus-host disease prophylaxis. Predonisolone was given to the three patients and plasma exchange was performed in one patient. Both hemolytic anemia and thrombocytopenia were resolved in virtually all patients, while creatinine elevation has persisted along with hypertension in one patient.

Adolescent

[Effective splenectomy in a patient with HIV-associated thrombocytopenia].

A 31-year-old man presented with a 3-month history of petechial hemorrhages. Physical examination revealed no splenomegaly. The patient's platelet count was 1.0 x 10(9)/l and bone marrow aspiration showed an elevated number of megakaryocytes. A diagnosis of HIV-associated thrombocytopenia was made on the basis of HIV seropositive results. The CD4 cell count was 400 x 10(6)/l. No opportunistic infections indicating AIDS were detected. Initially the patient was treated with predonisolone, but showed only a transient response. He also failed to respond to zidovudine, lamivudine, or indinavir. Following splenectomy, however, his platelet count rose above 80 x 10(9)/l (normal level: 150-350 x 10(9)/l).

Adult

Comparison of cytomegalovirus (CMV) antigenemia and CMV in bronchoalveolar lavage fluid for diagnosis of CMV pulmonary infection after bone marrow transplantation.

A comparative cytomegalovirus (CMV) diagnostic study was carried out on 30 bone marrow transplant patients. Forty-three bronchoalveolar lavage fluid (BALF) samples from these patients were examined for CMV by viral culture, polymerase chain reaction (PCR), shell vial and cytology. In parallel, peripheral blood samples were subjected to CMV antigenemia assay. CMV was detected in 12 (27.9%) of the 43 BALF samples (10 samples in viral culture, 10 samples in PCR, eight samples in shell vial and three samples in cytology). The CMV antigenemia assay yielded a positive result for six samples. The rates of agreement between results of the CMV antigenemia assay and results of each of the BALF tests were as follows: 81.4% with viral culture, 76.7% with PCR, 86.0% with shell vial, and 88.4% with cytology. Although the sensitivity of the CMV antigenemia assay was inferior to the sensitive tests of BALF samples, statistically significant correlations were demonstrated between the CMV antigenemia assay, viral culture, shell vial and cytology. Although the CMV antigenemia assay was shown to be useful for detection of CMV, it may be necessary to confirm not only the sensitivity but also the specificity of this method for prevention of CMV disease after BMT.

Adolescent

Microangiopathy without hemolysis in a patient following allogeneic bone marrow transplantation.

Thrombotic microangiopathy (TMA) is one of the complications of bone marrow transplantation (BMT) which includes hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Red cell fragmentation is the most consistent laboratory finding. We present a case of TMA with endothelial damage but without the signs of hemolysis. The patient was not receiving cyclosporine. Partial activation of platelets was also observed. This case represents a new form of TMA in transplant recipients.

Adult

Risk factors for hepatic veno-occlusive disease after bone marrow transplantation: retrospective analysis of 137 cases at a single institution.

One hundred and thirty-seven consecutive patients who received bone marrow or peripheral blood stem cell transplantation were studied retrospectively to identify the risk factors for hepatic veno-occlusive disease (VOD). Of the 137 recipients, twenty (14.6%) patients were diagnosed with VOD using the McDonald's criteria. In these 20 patients with VOD, we analyzed various clinical parameters, including age, sex, HLA status, conditioning regimen, irradiation, immunosuppressive agents, mode of transplantation, history of hepatic dysfunction, pre-transplant hepatic and renal function, infectious episodes, antibiotics use, and serum viral titers. A history of hepatic dysfunction and low levels of pseudocholinesterase before transplantation were found to be statistically significant (P = 0.04 and 0.04). Low levels of pseudocholinesterase were significant by multivariate analysis using the logistic regression model (P = 0.02). These results suggest that pseudocholinesterase levels before transplant are important markers of VOD in patients receiving BMT.

Adolescent

Effects of cyclosporin A on hepatitis C virus infection in bone marrow transplant patients. Bone Marrow Transplantation Team.

The hepatitis C virus (HCV) infection has, in general, been considered not to affect liver function severely during the course of bone marrow transplantation (BMT) except for late hepatitis which coincided with a decrease in immunosuppressive therapy. We examined serial sera of two patients with positive HCV antibody who underwent allogeneic BMT and found that while the dose of cyclosporin A tapered off, the serum concentration of HCV core protein increased before the occurrence of hepatitis. This suggests that viral reactivation and growth might be one of the important mechanisms of hepatitis after BMT in patients with positive HCV antibody.

Adult

Aspergillus endocarditis in a leukemia patient diagnosed by a PCR assay.

A patient in a blastic phase of chronic myelocytic leukemia developed multiple arterial emboli that originated from mitral valve vegetation. The diagnosis of infective endocarditis was not confirmed because blood cultures, serological assays and other examinations detected no pathogens. He died of intracranial hemorrhage after thrombolytic manipulation for embolization of the abdominal aorta and an autopsy was performed. Polymerase chain reaction analysis and Southern blot analysis of tissues from the mitral valve revealed Aspergillus species as the cause of the endocarditis, although none of the tissue specimens were culture-positive. These molecular analyses will be useful in the diagnosis of various types of Aspergillus infections.

Aspergillosis

[Relationship between the presence of side-holes in bone marrow aspiration needle and the number of harvested bone marrow mononuclear cells].

The aim of this study was to evaluate the yield of nucleated cells in bone marrow harvested by means of Downs' Islam aspiration needles with or without side-holes. Twenty marrow donors for HLA identical sibling transplants were studied. Bone marrow nucleated cells were harvested 50 ml in the right iliac bone with a Downs' Islam aspiration needle with or without side-holes and 50 ml in the left with another kind of needle by means of 5 ml aspirations in each donor. There were no significant difference between the number of nucleated cells by means of Downs' Islam aspiration needles with and without side-holes by cross-over analysis. All nucleated cell counts were 33.06 +/- 12.93 x 10(3)/microliter (mean +/- standard deviation) by means of the needle with side-holes and 32.90 +/- 15.25 x 10(3)/microliter by means of the needle without side-holes. The Downs' Islam aspiration needle without side-holes seems to be better in bone marrow harvest from normal volunteers than that with side-holes, because the former may be stronger than the latter.

Adolescent

Etoposide with/without G-CSF with busulfan and cyclophosphamide as conditioning for bone marrow transplantation. The BMT Team.

To increase the efficacy of bone marrow transplantation (BMT), we have tried to add etoposide (VP-16) to busulfan/cyclophosphamide (BU/CY). Twelve patients received 16 mg/kg of BU and 120 mg/kg of CY with 15-30 mg/kg of VP-16. Another two patients received 5 micrograms/kg of G-CSF with 30 mg/kg of VP-16. Patients tolerated escalating doses of VP-16 without any significant hepatotoxicity. Their maximal level of bilirubin was 37.6 micromol/L (2.2 mg/dl), and there was no significant skin toxicity or mucositis. By contrast, two patients who received G-CSF with 30 mg/kg of VP-16 developed hyperbilirubinemia and veno-occlusive disease, which terminated this phase I study. VP-16 can be safely combined with BU/CY < or = 30 mg/kg in three divided doses, and its effect on survival should be evaluated. G-CSF added to this regimen, however, should be used with great caution.

Adolescent

Plasma soluble interleukin-2 receptor level in patients with primary myelodysplastic syndromes: a relationship with disease subtype and clinical outcome.

To assess the hypothesis that the plasma soluble interleukin-2 receptor (sIL-2R) level may have predictive value for morbidity/mortality in patients with myelodysplastic syndromes (MDS), we determined in plasma sIL-2R level of 80 MDS patients and examined their subsequent clinical course. Compared with low-risk MDS (refractory anaemia (RA) and RA with ringed sideroblasts) patients and normal subjects, the plasma sIL-2R level was significantly elevated in high-risk MDS (three other MDS subtypes and acute leukaemia following MDS) patients (high-risk MDS versus low-risk MDS, P < 0.01; high-risk MDS versus normal subjects, P < 0.01). 14/40 low-risk MDS patients developed at least one of the following during the follow-up period: erythrocyte transfusion dependence, infections requiring hospitalization, disease progression or MDS-related death. The plasma sIL-2R level was higher in these eventful subjects than in event-free low-risk subjects (P < 0.0001), and all of 10 low-risk subjects with a plasma sIL-2R level > 540 U/ml experience at least one event. By logistic regression analysis of various parameters in these 40 low-risk subjects, the plasma sIL-2R level was identified as the strongest independent parameter for predicting eventful subjects (P < 0.0047). The plasma sIL-2R level did not show a predictive value in high-risk MDS. This study revealed that the plasma sIL-2R level is significantly elevated in high-risk MDS and suggested that the plasma sIL-2R level is a valuable predictive factors for the clinical outcome in low-risk MDS.

Adult

Granisetron in the prevention of vomiting induced by conditioning for stem cell transplantation: a prospective randomized study.

We conducted a prospective randomized study to compare granisetron, a 5-hydroxytryptamine-3 receptor antagonist with standard anti-emetics (control group) consisting mainly of metoclopramide, in the prophylaxis of emesis induced by conditioning prior to stem cell transplantation. Fifty-eight patients were evaluable for analysis. The number of emetic episodes expressed in terms of patient-days was significantly lower in the granisetron group than in the control group (P < 0.001). During the first 24 h of conditioning, 27 of the 31 patients (87.1%) in the granisetron group achieved control of emesis with less than three emetic episodes (major < or = ) a day compared with 37.0% in the control group (P < 0.001). The same degree of emesis control was maintained throughout the conditioning period in 51.% of patients in the granisetron group compared with 0% in the control group (P < 0.001). Adverse reactions were observed in 11.4% of patients in the granisetron group and in 25.9% in the control group. None of the events were serious. Based on these data, we conclude that granisetron is superior to standard antiemetics in protecting against the vomiting induced by conditioning for stem cell transplantation.

Adolescent

Rapid detection cytomegalovirus pneumonia in recipients of bone marrow transplant: evaluation and comparison of five survey methods for bronchoalveolar lavage fluid.

To detect cytomegalovirus-associated interstitial pneumonia (CMV-IP) in recipients of BMT in its earliest stage, five CMV methods were assessed for their usefulness using bronchoalveolar lavage fluid as the test specimen. Of the 43 cases enrolled in the study, PCR was positive in 12 cases, shell vial in eight, culture in eight and cytology in three. There were no positive cases in in situ hybridization. Based on this result, the 43 cases were classified into four groups: Group 1, three cases: positive in PCR, shell vial and cytology; Group 2, five cases: positive in PCR and shell vial; Group 3, four cases: positive only in PCR; and Group 4, 31 cases: negative in all CMV tests. Cases in Group 1 were judged as having the highest risk of overt CMV-IP. They were successfully treated with a combination of ganciclovir and immunoglobulin. Group 2 was diagnosed as having active CMV infection and ganciclovir monotherapy was effective for these patients. Groups 3 and 4 were not given anti-CMV therapy, but they were free from CMV-related manifestations throughout the study. The sensitivity and specificity of each survey method for the detection of Groups 1 and 2 were 1.0 and 0.89 in PCR, 1.0 and 1.0 in shell vial, 0.88 and 1.0 in culture, and 0.38 and 1.0 in cytology. Similarly, the positive and negative predictive values were 0.67 and 1.0 in PCR, 1.0 and 1.0 in shell vial, 1.0 and 0.97 in culture, and 1.0 and 0.88 in cytology. Thus, CMV survey on bronchoalveolar fluid was thought to be useful in detecting post BMT CMV-IP in its earliest stage.

Adolescent

Recombinant human erythropoietin (rhEPO) administration to marrow donors. Bone Marrow Transplantation (BMT) Team.

Reviewing 37 adult marrow donors, the hemoglobin (Hb) level at 3 weeks before marrow aspiration was predictive for the low Hb level just before the operation. Accordingly, erythropoietin was given to donors whose Hb level was less than 130 milligrams at 3 weeks before operation. One hundred units/kg of recombinant human erythropoietin (rhEPO) was given subcutaneously 3 times a week for 3 weeks. Four donors received rhEPO, and their data were compared with those from four historical controls. The initial average Hb level was 126.3 milligrams in the rhEPO group and 125.3 milligrams in the control group. The preoperative Hb level was 133.0 milligrams in the rhEPO group and 104.0 milligrams in the control group; the postoperative Hb levels were 123.8 and 90.8 milligrams, respectively. Engraftment was obtained in all patients who received the marrow from the donors treated with rhEPO and there was no significant delay in the recovery of white blood cell, reticulocytes and platelet counts. A 3-week regimen of erythropoietin may help prevent the donor's need to receive allogeneic blood transfusion, when the initial Hb levels were below 130 milligrams.

Adolescent