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Biomedical subjects

H Tsutani

Publications and source records attributed to H Tsutani.

At least 37 records · Page 2Linked to original sources
PubMed1999

Hepatic tumor rupture following effectual treatment with irinotecan in a patient with highly refractory malignant lymphoma.

We describe a patient with highly refractory malignant lymphoma who died of hepatic tumor rupture following treatment with irinotecan (CPT-11). This 60-year-old man with non-Hodgkin's lymphoma (diffuse large B-cell lymphoma) demonstrated disease recurrence in the liver and the vertebrae following high-dose chemotherapy and autologous hematopoietic stem cell transfusion. He was treated with CPT-11 at a dose of one third of the conventional dose used for non-Hodgkin's lymphoma in Japan. The tumor in the liver markedly decreased in size but then ruptured. Although pathologic hepatic tumor rupture is a rare complication in patients with malignant lymphoma of the liver, this case demonstrates that hepatic tumor rupture may occur in refractory malignant lymphomas that reveal extensive degradation by this new, effective salvage therapy.

Antineoplastic Agents, Phytogenic↗
PubMed1998

[Early manifestation of septic shock and disseminated intravascular coagulation complicated by acute myocardial infarction in a patient suspected of having Legionnaires' disease].

Legionellosis is an important cause of severe pneumonia in the community. Inadequate therapy will lead to respiratory distress syndrome, disseminated intravascular coagulation (DIC) and finally fatal multiple organ failure. We encountered a rare case in which early manifestation included septic shock and DIC complicated by acute myocardial infarction (AMI) suspected to be derived from Legionnaires' disease. A 54-year-old healthy female complained of lumbago, high fever and dry cough 10 days after visiting a hot spring spa. She was emmergently admitted due to shock. Physical examination demonstrated hypotension, high fever, course creakle in the right lower lung. Hepatosplenomegaly, lymphadenopathy and eruption were not found. WBC count was 34600/microliters with nuclear shift. CRP elevated. FDP, D dimer and TAT also elevated CPK elevated with dominance of the MB isozyme. Chest roentogenography revealed congestive heart failure, pleural effusion and obscure pneumonic shadow and EKG showed ST segment elevation in leads I, II, III, aVF, V4, V5, and V6. The patient was diagnosed as having septic shock, DIC and AMI. She was treated with gabexate mesilate, high dose methyl prednisolone and dopamine hydrochloride as well as piperacillin, meropenem, isepamycin and fluconzaole. Despite intensive care, the blood pressure fell again and pneumonia had progressed on the 8th hospital day. These antibiotics appeared to be ineffective. Erythromycin was then administered and a dramatic effect. was obtained as the patient recovered. Serum titer of Legionella pneumophila (serogroup 1) rose to 128-fold 2 weeks after the onset. Other serum titers such as Chlamydia psittaci, Rickettsia, Mycoplasma were all negative. Cultures obtained from the sputum, throat swab, urine and blood did not yield any microorganisms. Although the diagnosis could not be confirmed because the titer did not elevate over 256-fold of 4-fold within 2 weeks after the onset, Legionella infection was highly suspected from the clinical features. This is a rare case in which septic shock and DIC with AMI preceded pulmonary symptoms in a non-immunocompromised patient.

Diagnosis, Differential↗
PubMed1997

Differentiation induction in non-lymphocytic leukemia cells upon treatment with mizoribine.

Inosine-5'-monophosphate (IMP) dehydrogenase catalyzes the rate-limiting reaction of guanine nucleotide biosynthesis and has been implicated in the reaction of cell growth and differentiation. We examined the ability of mizoribine, an IMP dehydrogenase inhibitor, to induce differentiation in HL-60 and U937 cells as well as in fresh leukemic blast cells from patients with non-lymphocytic leukemia. Treatment with mizoribine reduced intracellular GTP levels and induced morphologic and functional differentiation in these two cell lines in a dose-dependent manner. HL-60 and U937 cells developed polymorphic nuclei and macrophage-like cytoplasm, respectively, as well as expression of CD11b and CD14 antigens and the ability to oxidize NBT. These changes became evident when intracellular GTP levels decreased to approximately 30% of untreated controls and were abrogated by addition of guanosine to the media. However, in fresh leukemic cells, the cells showing maturation in response to mizoribine were limited in those derived from two of ten patients having non-lymphocytic leukemia. These findings suggest mizoribine could induce differentiation in HL-60 and U937 cells through a decrease of intracellular GTP levels. Further study is required to determine its clinical use in patients with acute non-lymphocytic leukemia.

Adult↗
PubMed1997

Anti-Leukemia Chemotherapy of High-Risk Myelodysplastic Syndromes.

We evaluated the outcome of anti-leukemia chemotherapy on 42 patients with the high-risk myelodysplastic syndromes (MDS)-refractory anemia with excess of blasts (RAEB), 8 cases; RAEB in transformation (RAEB-T), 18 cases; chronic myelomonocytic leukemia (CMMOL), 6 cases; and leukemic transformation of MDS, 10 cases. The median age was 67 (range 20 to 84). As a remission-induction therapy, 35 patients received low-dose chemotherapy, such as low-dose cytarabine infusion, and seven patients received high-dose combination chemotherapy. The complete remission (CR) rates of the low-dose chemotherapy group and the high-dose combination chemotherapy group were 29% and 57%, respectively, and the overall CR rate was 33%. The median survival durations after induction chemotherapy of the CR group (14 cases), the partial remission (PR) group (11 cases), and non-remission (NR) group (17 cases) were 19 months, 8 months, and 3 months, respectively. As a post-remission consolidation chemotherapy, high-dose combination chemotherapy seemed to be superior to low-dose chemotherapy judging from the median CR duration (16 months versus 4 months), but a long-term disease-free survival is hardly expected, in contrast with results in cases of de novo acute myeloid leukemia.

Journal Article↗
PubMed1997

Clinical importance of interleukin-2 receptor alpha-chain expression in acute leukemia. The Japan Cooperative Group of Leukemia/Lymphoma.

To clarify the clinical importance of interleukin-2 (IL-2) receptor (IL-2R) expression in acute leukemia, we examined 517 adult patients with acute leukemia and CML blast crisis (CML-BC). IL-2R alpha was expressed in 42/311 AML, 5/11 acute unclassified leukemia, 24/116 pre-B ALL, 2/32 T-ALL, and 27/47 CML-BC, while IL-2R beta was expressed only in 2 T-ALL. Expression of IL-2R alpha was closely associated with that of different lineage markers, CD11b, CD34, and Ph1+ abnormality. IL-2R alpha(+) non-T leukemic cells did not respond to IL-2. Clinical outcome of IL-2R alpha (+) leukemia showed lower response to conventional chemotherapy and poorer prognosis than IL-2R alpha (-) cases. Serum IL-2R alpha level in IL-2R alpha (+) cases increased at the onset. Our findings indicate the diagnostic importance of IL-2R alpha expression in acute leukemia as a prognostic risk factor with a close relation to the particular cellular characteristics.

Acute Disease↗
PubMed1997

[Improvement of bleeding tendency and normalized platelet count increment following splenectomy in a patient with refractory anemia].

A 72-year-old woman with refractory anemia had severe bleeding tendency. Since 1994, platelet transfusions (10 units three times per week) were unable to maintaining her platelet count over 10 x 10(3)/ microliter. Her hemoglobin was decreased to 3.9 g/dl as a result of bleeding from early gastric cancer. At one-hour after posttransfusion corrected platelet count increment (1-hour CCI) was slightly low, as 14 x 10(3)/microliter/m2. A 24-hour posttransfusion CCI (24-hour CCI) and the (24-hour CCI)/(1-hour CCI) ratio were markedly low, as 0.5/microliter/m2 and 0.36, respectively. Anti-HLA antibody was not detected. The ineffectiveness of platelet transfusion was suspected to be highly associated with splenomegaly. Her spleen had been gradually increased in size since the first clinical examination. She underwent both subtotal gastrectomy and splenectomy, while receiving 40 units of platelet transfusion. After splenectomy, the 1-hour CCI and the (1-hour CCI)/(24-hour CCI) ratio markedly improved (76 x 10(3)/microliter/m2 and 0.79, respectively). Cutaneous bleeding halted and there have been no further episodes, despite less frequent platelet transfusions. This is the first report in which bleeding tendency and CCI were improved by splenectomy in a case of myelodysplastic syndrome.

Aged↗
PubMed1996

Myeloid antigen, CD13, CD14, and/or CD33 expression is restricted to certain lymphoid neoplasms.

The authors examined the expression of myeloid antigens (MyAg): CD11b, CD13, CD14, CD15, and CD33 in 249 adults with lymphoid neoplasms using flow cytometric analysis. In this study, acute leukemia that was myeloperoxidase negative by light microscopy and had at least one lymphoid antigen was defined as acute lymphoblastic leukemia (ALL). The patients were classified as follows: 6 with unclassified ALL, 35 early B precursor ALL, 32 T-ALL, 25 B-cell chronic lymphocytic leukemia (B-CLL) and its variants, 24 B-cell non-Hodgkin's lymphoma (B-NHL), 7 plasma cell disorders, 8 T-CLL, 2 adult T-cell leukemia, and 10 T-NHL. CD11b and CD15 were present in a wide range of lymphoid disorders irrespective of B/T lineage and maturity. Unclassified ALL and phenotypically immature ALL frequently expressed CD13 and CD33, and occasionally expressed CD14. Among early B precursor ALL, CD13, and/or CD33 were significantly associated with the presence of stem cell marker CD34 and the chromosomal abnormality t(9;22). In addition, ALL with deletion of chromosome 7 commonly expressed CD13 and CD33. Taken together, CD13 and/or CD33 positive ALL may originate from a multipotential stem cell. Among mature neoplasms, CD14 was frequently, and CD13 and CD33 were occasionally expressed in B-cell, but not T-cell tumors. These results suggest that CD13, CD14, and CD33 are preferentially expressed in two types of lymphoid neoplasms, namely undifferentiated ALL and mature B-cell lymphoproliferative disorders.

Adolescent↗
PubMed1996

Superior cytotoxic potency of mitoxantrone in interaction with DNA: comparison with that of daunorubicin.

The mechanism of action of the anthraquinone antileukemic drug mitoxantrone (MIT) was investigated and compared with that of daunorubicin (DNR) with emphasis on the interaction with DNA to clarify the more potent cytotoxic activity of MIT than DNR in human leukemia cells. MIT showed similar characteristics to those of the anthracyclines such as DNR in that binding of MIT to DNA was associated with reduced template activity and cleavage of DNA in HL-60 human leukemia cells. However, as compared with DNR, MIT showed an increased number of binding sites on DNA, a lower inhibition constant for DNA polymerization, and a greater DNA cleavage activity. These properties may contribute to its greater potency than that of DNR, with which MIT inhibited the proliferation of HL-60 human leukemia cells.

Antineoplastic Agents↗
PubMed1996

[Characteristic features of gouty patients].

Characteristic feature of pathogenesis, epidemiology and laboratory findings in hyperuricemia of gouty patients are studied and reasonable treatments of gout in clinical medicine are discussed. Gout is characterized by repeated arthritis attacks on the metacarpophalangeal joint of the first toe or other small joints, especially overworked joints or those exposed to cold. The arthritis attack lasts for 3.5 days and then diminishes gradually. The intervals are shortened in patients under poor hyperuricemic control but tophi formation is less frequent. Complications in combination with hyperlipidemia, diabetes mellitus, obesity and hypertension, which are compatible to syndrome X, are frequent in gouty patients and are suspected of rapidly progressing to arteriosclerosis, such as ischemic heart diseases. Hyperuricemia consists of over-production and underexcretion, which can be diagnosed by the urate clearance test. Classification is valuable for surveying the underlying diseases of secondary hyperuricemia and treating gouty patients. Underexcretion was observed in 85% of gouty patients with hyperuricemia and even the mean urate clearance in the overproduction type was significantly lower than that of normal controls, suggesting that underexcretion is a fundamental phenomenon in all gouty patients. Treatments of complications as well as those of hyperuricemia with uricosuric agents are required for clinical treatment of gouty patients.

Adolescent↗
PubMed1994

Clinical pharmacology of 1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate, an orally administered long-acting derivative of low-dose 1-beta-D-arabinofuranosylcytosine.

1-beta-D-Arabinofuranosylcytosine-5'-stearylphosphate (cytarabine ocfosfate, stearyl-ara-CMP) is a newly synthesized 5'-alkylphosphate derivative of 1-beta-D-arabinofuranosylcytosine (ara-C), which is lipophilic, resistant to inactivation by deamination, and orally active. Pharmacology of this drug was studied in patients with hematological malignancies. The concentrations of stearyl-ara-CMP, ara-C (its active metabolite), and 1-beta-D-arabinofuranosyluracil (ara-U, its inactive metabolite) were determined by radioimmunoassay. When six patients received a single p.o. dose of the drug (500 mg/m2), stearyl-ara-CMP, ara-C, and ara-U could be detected in the plasma for at least 72 h afterwards. The plasma disappearance curve of stearyl-ara-CMP corresponded to a one-compartment open model with first-order absorption kinetics. The peak plasma level (Cmax) was 322 +/- 218 nM, and the predicted time to reach Cmax (Tmax) was 6.5 +/- 4.5 h, while the elimination half-life (t1/2) was very long (32.0 +/- 8.4 h). The plasma ara-C level increased slowly to a Cmax of 26.3 +/- 12.7 nM (Tmax, 13.3 +/- 4.7 h) after stearyl-ara-CMP administration. This level was quite low compared with that achieved by low-dose s.c. ara-C therapy, but ara-C persisted longer in the plasma in the former case, and the area under the curve was similar for both regimens. For ara-U, the Cmax, Tmax, and t1/2 were 483 +/- 315 nM, 23.6 +/- 4.0 h, and 19.6 +/- 5.3 h, respectively. No stearyl-ara-CMP was detected in the urine, and only 8.0% of the administered dose was excreted as ara-C and ara-U within 72 h. The stearyl-ara-CMP concentration in the cerebrospinal fluid was below the limit of detection in three patients without meningeal involvement at 6 h. During clinical use of stearyl-ara-CMP, macrocytic anemia was observed, and some patients also developed megaloblastic change of their erythroblasts, suggesting a mild and persistent cytostatic effect. In conclusion, p.o. therapy with stearyl-ara-CMP achieved prolonged maintenance of the plasma drug level. Thus, the drug released a very low dose of ara-C over a long period in plasma and tissues and had a prolonged mild antineoplastic effect in patients with hematological malignancies.

Acute Disease↗
PubMed1994

Establishment and characterization of a novel myeloid cell line from the bone marrow of a patient with the myelodysplastic syndrome.

A novel long-term cultured myeloid cell line was established from the bone marrow of a patient with myelodysplastic syndrome (MDS). This cell line, designated MDS92, proliferated in the presence of interleukin-3 or granulocyte-macrophage colony-stimulating factor and transiently in the presence of Steel factor, with a tendency for gradual maturation, and formed myeloid colonies in the semi-solid culture condition. In addition, the MDS92 cell line represented rather complicated karyotypic abnormalities including the deletion of fifth and seventh chromosomes and a point mutation at codon 12 of the N-ras oncogene. These characteristics of the MDS92 cell line are exclusively compatible with the property of preleukaemia.

Anemia, Sideroblastic↗
PubMed1993

Clinical importance of CD7 expression in acute myelocytic leukemia. The Japan Cooperative Group of Leukemia/Lymphoma.

Forty patients (9 females and 31 males; mean age 41.9 years) with CD7+ acute myelocytic leukemia (AML) were investigated; they were classified into the following subgroups according to French-American-British classification: 15 M1, 18 M2, 3 M4, and 4 M5. Leukemic cells from all the patients were negative for T-cell-specific antigens, surface CD3, and T-cell-receptor molecules. The sex and age distributions were different from those of CD7- AML patients (P < .01). Hepatomegaly and central nervous system involvement were also frequent in the CD7+ AML patients. The phenotype of and responsiveness to hematopoietic growth factors by the leukemic cells showed their immaturity, as evidenced by frequent expression of CD34, HLA-DR, and TdT, and the greatest growth response to interleukin-3. No particular karyotypic abnormality was shown. One hundred eighty AML patients were treated with a therapeutic regimen routinely used for AML. The CD7+ AML patients showed a significantly lower response than CD7- AML patients (P < .01), and had a poorer prognosis (P < .01). CD7+ AML patients with M1 or M5b had unfavorable responses to the therapeutic regimen in comparison with patients with M2, M4, or M5a. In addition, 3 of 4 CD7+ CD2+ AML patients, who did not respond to the therapy, were induced into complete remission with an acute lymphoblastic leukemia therapy. The results presented here indicate the diagnostic importance of CD7 positivity in AML, suggesting that the cellular and clinical characteristics of CD7+ AML are sufficient for it to be recognized as a distinct category of AML.

Adolescent↗