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Biomedical subjects

Y Onozawa

Publications and source records attributed to Y Onozawa.

At least 37 records · Page 2Linked to original sources

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↗

Effects of interleukin-12 on natural killer cell cytotoxicity and the production of interferon-gamma and tumour necrosis factor-alpha in patients with myelodysplastic syndromes.

The effects of interleukin 12 (IL-12) on natural killer (NK) cell cytotoxicity and on the production of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) were examined in 15 patients with myelodysplastic syndromes (MDS), which are well known to have immunologic defects, and in 11 normal subjects. The NK cell cytotoxicity of all of the normal subjects was augmented by incubation with IL-12 alone, and co-incubation with interleukin 2 (IL-2) further augmented it (type A response). The MDS patients showed varied responses to IL-12/IL-2. Seven patients showed the type A response, resulting in augmented NK cell cytotoxicity which was similar to that in the normal subjects. In five other patients the cytotoxicity was not increased by IL-12 alone, but the combination of IL-12 and IL-2 did augment the cytotoxicity (type B response). The augmented cytotoxicity in these type B patients was lower than that in the normal subjects. In the final three MDS patients the cytotoxicity was low and not affected by IL-12 and/or IL-2 (type C response). All patients with refractory anaemia with excess blasts (RAEB) and patients with RAEB in transformation showed a type B or C response. Conversely, six of eight refractory anaemia patients showed a type A response. In MDS patients there was a positive correlation between the percentage of CD3- CD56+ cells in pre-incubated cells and the cytotoxicity of cells incubated with IL-12/IL-2. The combination of IL-12 and IL-2 augmented IFN-gamma and TNF-alpha production by nonadherent mononuclear cells in a synergistic or cumulative manner, respectively, in most patients. These results suggest that IL-12, alone or with IL-2, may modulate these important immunologic functions in most MDS patients.

Adult↗

[Indication of allogeneic bone marrow transplantation (BMT) from HLA identical sibling in adult acute myeloblastic leukemia--comparative study of BMT and chemotherapy in patients with the first remission state. Nagoya BMT Group. Japan Adult Leukemia Study Group].

The indication of allogeneic bone marrow transplantation (BMT) from HLA identical siblings during the first remission of acute myeloblastic leukemia was discussed according to the results of BMT and chemotherapy study groups. The comparison of disease free survival between both groups was done, after selection biases such as risk factors and time of BMT were adjusted by multivariate analysis or matched-pair analysis. In conclusion, patients with more than one high risk factors for leukemia relapse, that is, high peripheral white blood cell count (PBC) (> 20,000/cmm) at diagnosis or more than two remission induction courses should be considered for BMT, and the indication of treatments for patients with no high risk factors should be determined depending on situations of the disease and patient's intention.

Adult↗

Elevated plasma soluble interleukin 2 receptor level correlates with defective natural killer and CD8+ T-cells in myelodysplastic syndromes.

The plasma soluble interleukin 2 receptor (sIL-2R) level and its relationships with haematologic and immunologic data were examined in 40 patients with myelodysplastic syndromes (MDS). The plasma sIL-2R level was significantly higher in the high-risk MDS group (refractory anaemia with excess blasts (RAEB), RAEB in transformation and chronic myelomonocytic leukaemia) than in the low-risk MDS group (refractory anaemia (RA) and RA with ringed sideroblasts) or in normal subjects, although there was considerable variation in the plasma sIL-2R level within each MDS group. The plasma sIL-2R level correlated positively with the bone marrow cellularity and bone marrow blast mass, but not with the absolute number of CD25+ lymphocytes. This may support the idea that plasma sIL-2R is derived from malignant MDS cells in the bone marrow. The plasma sIL-2R level correlated negatively with the absolute numbers of the CD8+, CD3-CD16+, and CD3-CD56+ cell populations in freshly isolated lymphocytes, the percentage of CD3-CD56+ cells in lymphokine (interleukin 2)-activated killer (LAK) cells, and the cytotoxicity of LAK cells. We conclude that MDS patients having a high plasma sIL-2R level often have a defect in natural killer and CD8+ T-cells.

Adult↗

Assessment of therapeutic potential of interleukin 2 for myelodysplastic syndromes.

The therapeutic potential of interleukin 2 (IL-2) for myelodsplastic syndromes (MDS) was evaluated in vitro. IL-2-induced lymphokine-activated killer (LAK) cells were prepared from 38 MDS patients and 20 normal subjects. The cytotoxicity of LAK cells against K562 and Raji cell lines and MDS blasts was significantly reduced in high-risk MDS (refractory anaemia with excess blasts (RAEB), RAEB in transformation, and leukaemic transformation of MDS), but was relatively well-preserved in low-risk MDS (refractory anaemia (RA) and RA with ringed sideroblasts). Examination of the immunophenotypes of freshly-isolated lymphocytes showed that the percentage of CD4+ cells in low-risk MDS and the percentage of CD3+, CD4+ and CD8+ cell populations in high-risk MDS was significantly reduced compared with these populations in normal subjects. After cultivation with IL-2, these three cell populations were still reduced in the corresponding MDS groups and the percentage of CD3-CD56+ cells were significantly reduced in high-risk MDS. There was a positive correlation between the percentage of K562 cells lysed by MDS LAK cells and the percentage of CD3-CD56+ lymphocytes in MDS LAK cells. These aberrant lymphocyte subpopulations appeared to explain, at least in part, the reduced LAK cell cytotoxicity in MDS. These results present a possibility that IL-2 and LAK therapies are ineffective for most high-risk MDS patients, whereas they have potential value for low-risk MDS patients whose lymphocyte cytotoxicity is usually preserved.

Adult↗

Defective natural killer (NK) cell-mediated cytotoxicity does not imply clonal involvement of NK cells in myelodysplastic syndromes.

The clonality of purified cells was examined in 10 myelodysplastic syndromes (MDS) patients by analysing the restriction fragment length polymorphism and methylation pattern of the phosphoglycerate-kinase gene. Natural killer (NK) cell-mediated cytotoxicity was also examined. The granulocytes and monocytes were monoclonal or oligoclonal in all cases, except for the monocytes in one case. Conversely, the NK and T cells had a polyclonal pattern in most cases, including all cases who had defective NK cell-mediated cytotoxicity. The hypothesis that reduced NK cell-mediated cytotoxicity in MDS is caused by a clonal involvement of NK cells was not supported by the present study.

Adult↗

Prevention of invasive fungal infection during chemotherapy-induced neutropenia in patients with acute leukemia.

This is a retrospective study comparing the methods of preventing fungal infection in a total of 420 episodes of chemotherapy-induced neutropenia of more than 10 days' duration between 1986 and 1992 in 104 patients with acute leukemia and 62 patients who underwent bone marrow transplantation. The episodes were divided into five groups according to the prophylactic regimens (group 1, oral amphotericin B (OA) only; 2, OA and nebulization of amphotericin B (NA); 3, OA and NA with a laminar air flow system (LAF); 4, oral fluconazole (OF) and NA; 5, OF, NA, and LAF. The total numbers of neutropenic episodes were 115, 141, 95, 37, and 32, respectively. A total of 15 episode of invasive fungal infections were documented. Aspergillosis was seen on two occasions each in groups 1 and 2, while none was seen in the patients who were under the LAF system. Nebulization of amphotericin B did not have a significant preventive effect in this study and it needs to be evaluated further by a randomized study.

Acute Disease↗

[Enterococcus faecium obtained from surveillance cultures of the stool of the patients with hematological malignancies].

Surveillance cultures of the stool were obtained from 55 patients with hematological malignancies, who have been receiving norfloxacin or tosufloxacin during their neutropenic periods, from May, 1991 to September, 1992. Cultures were performed using 5% blood agar with piperacillin 300 micrograms/ml and amikacin 20 micrograms/ml and bacteria resistant to these antibiotics were analyzed further. Thirty-four over 55 patients were positive for enterococci and 22 strains of 23 examined were Enterococcus faecium. They are resistant to quinolones, aminoglycosides, cephalosporins and penicillins but not to vancomycin. Eighteen of them were also resistant to high-dose gentamicin. Appropriate measures should be used to prevent intrahospital spread of these resistant isolates.

4-Quinolones↗

Tosulfloxacin versus norfloxacin for prevention of infections in chemotherapy-induced neutropenic patients.

We conducted a non-randomized, prospective study comparing the efficacy of tosulfloxacin with that of norfloxacin in preventing bacterial infection during chemotherapy-induced neutropenic episode. Fifty-one patients with hematological malignancies were included, and a total of 108 episodes of neutropenia were studied. There was no significant difference between the two groups in the incidence of fever, in the time-to-event analysis of febrile episodes nor in the incidence of gram-positive bacteremia despite the broader spectrum of tosulfloxacin. The incidence of gram-negative bacteremia was lower in patients treated with the quinolones as a prophylactic than in the historical controls given polymyxin B. Especially the incidence of bacteremia due to Pseudomonas aeruginosa was significantly less when tosulfloxacin was used. A possible synergistic effect of sulfamethoxazole-trimethoprim in preventing the febrile episode was also observed.

Adolescent↗

Treatment of pure red cell aplasia after major ABO-incompatible bone marrow transplantation resistant to erythropoietin. Bone Marrow Transplantation Team.

A case of pure red cell aplasia after major ABO-incompatible bone marrow transplantation with long duration of up to 482 days is presented. The patient exhibited resistance to treatment using intravenous gamma globulin, prednisolone and 8 week administration of erythropoietin. The patient finally responded to treatment using erythropoietin and methylprednisolone simultaneously. Because of its safety and efficacy, it might be worthwhile to try erythropoietin with methylprednisolone, if necessary, for pure red cell aplasia complicating major ABO-incompatible bone marrow transplantation.

ABO Blood-Group System↗

[A case of primary pulmonary lymphoma associated with Sjögren syndrome and IgM monoclonal gammopathy confirmed by DNA rearrangement].

A 70-year-old man was admitted for evaluation of an abnormal shadow on his chest X-ray film, consisting of a mass containing an air bronchogram. He was also found to have a monoclonal gammopathy (IgM kappa type) and Sjögren syndrome. Open lung biopsy was performed with the suspicion of primary pulmonary lymphoma or pseudolymphoma. Southern blot analysis of the tissue revealed clonal rearrangements of immunoglobulin gene, supporting the diagnosis of B-cell lymphoma. Using conventional immunoperoxidase staining (PAP) method, the monoclonality in the tissue specimen is sometimes quite difficult to prove. Southern blot analysis, however, gives more accurate and reliable results. The analysis of immunoglobulin gene rearrangements is quite useful in determining the presence or absence of monoclonality in a specimen in cases of suspected lymphoproliferative disease such as primary pulmonary lymphoma and pseudolymphoma. We strongly recommend the use of Southern blot analysis in making the diagnosis of lymphoproliferative disease.

Aged↗