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Biomedical subjects

T Ueda

Publications and source records attributed to T Ueda.

At least 1,423 records · Page 79Linked to original sources

[Early phase II study of PL-AC [N4-palmitoyl-(1-beta-D-arabinofuranosyl) cytosine] on hematopoietic malignancies].

Twenty-one patients with hematopoietic malignancies including 6 previously untreated, 9 pretreated, and in relapse, 5 in complete remission and one in partial remission all were treated with PL-AC. The patients consisted of 12 acute myelocytic leukemias, 4 acute monocytic leukemias, 2 acute lymphocytic leukemias, one erythroleukemia, one malignant lymphoma and one chronic monocytic leukemia. PL-AC was given orally at a dosage of 50-1200 mg daily. Mean total dosage was 4.74 g (0.6-15.25), and the mean administration period was 3.43 days (1-122). days Responses were observed in 4 out of 9 pretreated patients by a decrease of blast cells in the peripheral blood. Partial remission was obtained in one case which lasted 8 months. Out of 5 previously untreated acute leukemias, one partial remission and 4 hematological responses were observed. The plasma concentration of Ara-C was maximal at 3 hours and was not detectable after 12 hours. Side effects observed were nausea in 5 patients vomiting in one patient and liver dysfunction in one patient. These side effects however were not so severe as to stop drug administration. PL-AC may be administered in doses ranged 150-250 mg for 2-3 weeks without any severe side effects, and with some clinical effects.

Administration, Oral↗

Classification of acute non-lymphocytic leukemia according to the distribution picture of peroxidase activity and cell size: correlation between the classification and therapeutic response.

A distribution picture was prepared on the basis of the correlation between peroxidase activity and cell size in leukemic cells using an automated leukocyte differential counter (Hemalog-D). From this, acute nonlymphocytic leukemia was classified into three groups in which the therapeutic response was examined. The leukemic cells of Group I were medium or large and were negative or weakly positive to peroxidase. These cells were characterized by their location in the upper part of the normal lymphocyte distribution. The leukocyte differential count, measured by a computer on the basis of the distribution picture, showed an increase in large unstained cells (LUC) and lymphocytes. The leukemic cells of Group II were large and positive to peroxidase and were characterized by their location in the right upper part, across the region of LUC, monocytes, basophil and neutrophil leukocytes as seen in the distribution picture. The findings of Hemalog-D showed an increase in LUC, remainder and neutrophil leukocytes. The leukemic cells of Group III were medium-sized and moderately or strongly positive to peroxidase. This group was characterized by their location in the lower part of normal neutrophil leukocytes and Hemalog-D showed an increase in neutrophil leukocytes. A total of 71 patients with acute nonlymphocytic leukemia were assessed according to this classification. Group I (14 patients): 11 with acute myelogenous leukemia (AML), 2 with acute monocytic leukemia (AMoL) and 1 with acute myelomonocytic leukemia ( AMMoL ); Group II (17 patients): 7 with AML and 10 with AMoL; Group III (40 patients): 28 with AML, 4 with AMoL, 1 with AMMoL and 7 with acute promyelocytic leukemia (APL). These groups were treated with the protocol (DCMP two step, BH-AC DMP, BH-AC AMP) established by the Yamada Leukemia Study Group of the Japan Welfare Ministry Cancer Research Project (chairman Yamada, K). The complete remission rate was 35.7% in Group I, 58.8% in Group II and 85.0% in Group III. The difference between Groups I and III was statistically significant (P less than 0.005), as was the difference between Groups II and III (P less than 0.1), while that between Groups I and II was not significant. The median survival was 12 months in Group I, 9 months in Group II and 15 months in the Group III and the difference between Groups I and III was statistically significant (P less than 0.05). Group III included a small number of AMoL and APL patients in addition to AML, while Groups I and II consisted mainly of patients with AMoL and AML.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Chemical modification of adenine residues in mouse 5S rRNA with monoperphthalate: the secondary structure of 5S rRNA.

The chemical modification of adenine residues in mouse 5S rRNA with monoperphthalate was carried out to investigate the higher ordered structure of 5S rRNA. The adenine residues at positions 11, 22 (or/and 23), 49 (or/and 50), 54 (or/and 55), 77, 83, 88, 90 and 100 (or/and 101) were modified. This result further confirmed the secondary structure of 5S rRNA constituted of 5 helices and 5 loops postulated by other chemical modifications.

Animals↗

[Choreito and Shakuyakukanzoto: their effects on facilitating the voiding of stones in the urinary tract].

We treated 30 patients having 37 urinary calculi in all, with " Choreito " (5 g/day) and " Shakuyakukanzoto " (5 g/day) to study whether these medicines hastened spontaneous calculus excretion. Within 2 months, 91% of the small calculi (5 X 5 mm and smaller), and 33% of the medium-sized (6 X 10 mm and below) were excreted. These results were similar to those obtained with conventional conservative treatment, and suggest that this therapy will be useful.

Adult↗

Efficacy of laminar air flow room with or without clean nursing for preventing infection in patients with acute leukemia.

The clinical effectiveness of bioclean rooms was studied in relation to prevention of infection during treatment for induction of remission of acute leukemia. According to the steps in clean patient care, patients were divided into three groups, Group A consisting of 106 patients who were accommodated in laminar air flow (LAF) rooms under strictly clean nursing, Group B consisting of 99 patients who were treated in disinfected rooms with LAF without any clean nursing techniques and Group C consisting of 188 patients who stayed in conventional wards. Since all patients were treated with antileukemic drugs and preventive administration of antimicrobial drugs under the same regimen, any difference between groups should be attributable to LAF or LAF and clean nursing. A marked and stepwise reduction in the incidence of infection between Groups A, B and C was observed. A statistically significant reduction in pneumonia, upper respiratory tract infection, periproctitis and skin abscesses was also observed in Groups A and B. As to the causative organisms, a relative increase in incidence of infections caused by Pseudomonas aeruginosa and Escherichia coli and a decrease in those caused by Proteus and fungi were observed in Groups A and B, as compared with Group C. These data suggest that pneumonia etc. may be exogenous infections and that Proteus and fungi are exogenous organisms, while Pseudomonas aeruginosa and Escherichia coli are endogenous bacteria. These data seem very helpful for setting up several steps in bioclean rooms for effective and economic patient care.

Adult↗

Pharmacokinetics of N4-behenoyl-1-beta-D-arabinofuranosylcytosine in patients with acute leukemia.

N4-Behenoyl-1-beta-D-arabinofuranosylcytosine (BHAC), a lipophilic and deaminase-resistant derivative of 1-beta-D-arabinofuranosylcytosine (ara-C), was studied pharmacologically in patients with acute leukemia. The concentrations of BHAC, ara-C, and 1-beta-D-arabinofuranosyluracil were measured by high-performance liquid chromatography, bioassay, and gas chromatography-mass spectrometry-mass fragmentography, respectively. The data of plasma BHAC concentrations were analyzed by a MULTI computer program. In seven patients given BHAC (200 mg/body weight; 2.97 to 4.26 mg/kg) i.v. for 90 min, the plasma disappearance curve of BHAC was biphasic with a mean initial half-life of 0.37 hr and a mean second half-life of 5.27 hr. The apparent volume of the central compartment and the apparent volume of distribution were 0.047 and 0.316 liter/kg, respectively; the systemic clearance was 0.051 liter/hr/kg. BHAC concentrations in erythrocytes were significantly higher (p less than 0.01) than those in plasma at 4 to 22.5 hr after infusion, suggesting that the erythrocytes may act as a reservoir for the drug. The plasma 1-beta-D-arabinofuranosyluracil level increased to 603 ng/ml at 4 hr after infusion, and it was over 129 ng/ml for at least 22.5 hr after infusion. Plasma ara-C levels, which could be detected in only 2 of 11 patients examined, were maintained (over 0.08 micrograms/ml) for 8 hr after infusion. Urinary BHAC excretion was less than 0.2 micrograms/ml of the sensitivity limit in all samples. Prolonged urinary ara-C excretion was detected, but it was only 0.5% of the administered BHAC for 24 hr. At 12 hr after a 200-mg infusion of BHAC, BHAC level in bone marrow fluid was significantly higher (p less than 0.01) than that in plasma. In spite of the lipophilic nature of the agent, the BHAC concentration in cerebrospinal fluid was less than 0.2 micrograms/ml in 8 of 9 patients without meningeal involvement. These findings were thought to indicate a restricted and prolonged BHAC distribution including plasma, blood cells, and bone marrow fluids, which may be of importance in the administration of BHAC in the chemotherapy of hematological cancers.

Acute Disease↗

[Clinical evaluation of high dose intravenous injection of fosfomycin on the severe infections associated with the treatment of haematological disorders].

Fosfomycin (FOM) was administered intravenously to 65 cases of severe infections complicated with 62 cases of several haematological disorders. Out of 65 cases, 45 were treated with high doses FOM, i.e., 8 g per day or more. Another 20 cases were treated in usual doses of 4--6 g per day. Causative organisms were isolated from 52 cases of which 32 cases were Gram-negative bacilli and 19 cases were Gram-positive cocci. The effective rate of FOM was 57.8% in the high-dose treatment group (26/45) and 45.0% in the usual-dose treatment group (9/20), but the significant difference was not defined. Among 32 cases with Gram-negative bacilli infections, including Pseudomonas aeruginosa or Serratia marcescens, 15 cases were effective (47%). On the contrary, 14 out of 19 cases with Gram-positive cocci infections were effective (74%). Thirteen cases (50.0%) were effective even in which neutrophils were less than 500/cmm before FOM administration. Severe side effects were not observed, without 2 cases. One was skin eruption due to drug allergy and the other was suspected to be interstitial pneumonitis, but not confirmed pathologically. These data suggest that high dose treatment of FOM were useful for the severe infections even in neutropenic state in haematological disorders.

Adolescent↗

Intracellular distribution of N4-behenoyl-1-beta-D-arabinofuranosylcytosine in blood cells.

In order to clarify differences in mode of action between N4-behenoyl-1-beta-D-arabinofuranosylcytosine (behenoyl-ara-C) and 1-beta-D-arabinofuranosylcytosine (ara-C), comparative studies on both agents were undertaken. When human erythrocytes incubated with behenoyl-ara-C[acyl-1-14C] were fractionated into stroma and stroma-free lysate, a marked accumulation of radioactivity in stroma was observed. In contrast, ara-C[cytosine-2-14C] was rapidly incorporated into the stroma-free lysate. Thin-layer chromatography of the extracts of L1210 cells incubated with behenoyl-ara-C[acyl-1-14C] or behenoyl-ara-C[cytosine-2-14C] at 37 degrees for 60 min revealed that most of the incorporated drug remained as unmetabolized behenoyl-ara-C. After incubation of 20 microM behenoyl-ara-C or ara-C with L1210 cells at 37 degrees for 60 min, subcellular fractionation of the cell suspension was performed; behenoyl-ara-C was accumulated markedly in the membrane, mitochondria and microsome fractions. In contrast, most of the ara-C was found in the 105,000g supernatant fraction. The accumulation of behenoyl-ara-C in membrane structures may result from the lipophilic nature of the agent, which may have a prolonged inhibitory action on leukemic cell proliferation.

Animals↗