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Biomedical subjects

R Ohno

Publications and source records attributed to R Ohno.

At least 271 records · Page 15Linked to original sources
PubMed1991

[Late phase II study of MST-16 (sobuzoxane) on malignant lymphoma].

Late phase II trial of MST-16 for malignant lymphoma was conducted by the multi-institutions collaboration. Out of 34 patients entered, 29 were evaluated for efficacy as well as side effects. One complete response and 8 partial responses were achieved by the treatment of MST-16. The factors which affect the response rate were prior chemotherapies, stage of disease and performance status. The main toxicities were bone marrow suppression and G-I disorders. Leukopenia was observed in 72.4% of patients, thrombocytopenia in 44.8% and nausea/vomiting in 31.0%. Patients recovered from these side effects by discontinuation of the MST-16 therapy.

Adult↗
PubMed1991

New enzyme-linked immunosorbent assay for glycocalicin in plasma.

A new sandwich-type enzyme-linked immunosorbent assay for quantifying glycocalicin, a proteolytic fragment of platelet membrane glycoprotein Ib, is described. The assay is based on the use of two monoclonal antibodies raised against glycoprotein Ib and involves the avidin-biotin technique. The detection limit is 7 micrograms/L and the range of glycocalicin determined in plasma is 0.01 to 1 mg/L. Assay time is 2 h. The intra-assay CV ranged from 3.6% to 5.2%, the interassay CV from 5.4% to 8.0%. Analytical recovery of purified glycocalicin added to a plasma pool averaged 96%. In 36 healthy subjects, the mean glycocalicin concentration in plasma was 0.36 (SD 0.07) mg/L (2.7 nmol/L). We conclude that this assay is suitable for measuring glycocalicin in plasma and is also more sensitive and precise than the previously published immunoassays based on competitive binding assay.

Adolescent↗
PubMed1991

[Is allogeneic bone marrow transplantation the first choice for acute leukemia in first remission? From chemotherapeutical point of view].

Since 1984 several prospective randomized clinical trials have been reported that the disease-free survival for BMT in first remission was superior to chemotherapy for AML. However, there raise two main controversies about these conclusions. First, in last several years intensive consolidation therapy was applied and nearly 50% of patients are reported to be alive 5 years. Second 10% to 50% BMT scheduled patients were excepted mainly because of their condition. On the contrary, about ALL, even these several years, age is the still main risk factor independently of therapy. Reports with good 5 year disease free survival all due to their patients' youth. The prognosis of ALL patients age 30 or more are poor and BMT seems to be a first choice in first-remission in patients under age 40. Only large-scale prospective randomized study among patients with or without HLA-identical donors will give the answer to this important issue.

Acute Disease↗
PubMed1990

Effect of granulocyte colony-stimulating factor after intensive induction therapy in relapsed or refractory acute leukemia.

Background. Although colony-stimulating factors have been shown to accelerate recovery from severe neutropenia after intensive chemotherapy or bone marrow transplantation, their use in acute leukemia has been controversial because in vitro they stimulate leukemic colonies as well as normal granulocyte colonies. Methods. We conducted a prospective, randomized, controlled study to determine the safety and efficacy of recombinant human granulocyte colony-stimulating factor (CSF) after a standard course of intensive therapy in 108 patients with relapsed or refractory acute leukemia (67 with acute myelogenous leukemia, 30 with acute lymphocytic leukemia, 9 in blast crisis from chronic myelogenous leukemia, and 2 with acute leukemia arising from myelodysplastic syndromes). Treatment with granulocyte CSF (200 micrograms per square meter of body-surface area per day in a 30-minute infusion) was begun two days after the end of the chemotherapy and continued until the neutrophil count rose above 1500 per cubic millimeter. Results. Treatment with granulocyte CSF accelerated the recovery of neutrophils significantly (P less than 0.01), shortening it by about a week, but it had no effect on platelet recovery. Although the incidence of febrile episodes was almost the same, documented infections were significantly less frequent in the group treated with granulocyte CSF (P = 0.028). There was no evidence that granulocyte CSF accelerated the regrowth of leukemic cells. Fifty percent of 48 patients in the CSF group who could be evaluated and 36 percent of 50 controls had complete remission. The rate of relapse was almost the same in the two groups. Conclusions. It appears that recombinant human granulocyte CSF is safe in acute leukemia, accelerating neutrophil recovery and thereby reducing the incidence of documented infection without affecting the regrowth of leukemic cells. It should be used with caution, however, pending further confirmation of these early results.

Acute Disease↗
PubMed1990

[How to deal with equivocal subjects in statistical analysis of randomized controlled trials].

In randomized controlled trials, it is likely that several subjects with atypical features are registered. In this paper, it was discussed from a statistical point of view how properly the subjects with the following atypical features could be dealt with; 1) subjects who were found to be not eligible for the trial after randomization, 2) subjects who did not receive the assigned regimen by the treatment protocol, 3) subjects whose outcome was ambiguous as the designated endpoint, and 4) subjects who were ambiguous whether to be regarded as censored cases. It was also emphasized that informations on equivocal subjects should be masked in the committee which is responsible for the statistical judgement. Plausible examples were added to assist the readers to understand the rules discussed here.

Humans↗
PubMed1990

Substitution of aspartic acid-217 of Citrobacter freundii cephalosporinase and properties of the mutant enzymes.

On the assumption that Asp-217 of a Citrobacter freundii cephalosporinase forms a salt-bridge with the conserved Lys-67, Asp-217 was changed to glutamic acid, threonine or lysine. The mutant enzymes retained about the same level of activity as that of the wild-type enzyme, and the participation of Asp-217 in the salt-bridge was ruled out. However, the mutations resulted in an increase in hydrolytic activity toward oxyimino-cephalosporins such as cefuroxime, cefmenoxime and ceftazidime, suggesting a possible mechanism of the bacterial resistance to the novel beta-lactams by a single mutation in cephalosporinases.

Aspartic Acid↗
PubMed1990

A case of infantile acute monocytic leukemia caused by vertical transmission of the mother's leukemic cells.

A case of infantile acute monocytic leukemia (AMoL), which was probably transmitted from a pregnant woman with leukemia to her unborn infant, is presented. A woman had AMoL when her third infant was born. This infant, who was a boy, also suffered from AMoL when he was 20 months of age. The infant's leukemic cells had the same cytochemical and immunophenotypic patterns as the mother's leukemic cells. By cytogenetic analysis, the majority of the infant's leukemic marrow cells had the 46,XX karyotype and showed no Y body by quinacrine staining. Moreover, the phenotype for human major histocompatibility system, HLA-A, HLA-B, and HLA-DR of the infant's leukemic cells was consistent with that of the mother's lymphocytes. Thus, the infant's leukemic clone was found to be identical to the mother's leukemic clone. His lymphocytes could not react with the mother's leukemic cells or his own leukemic cells in mixed lymphocyte culture, suggesting that the HLA homozygosity of the mother may have played a role in inducing immunologic tolerance to the immigrated leukemic cells in the infant. This is the first report of an infantile leukemia transmitted from a mother with leukemia, supposedly through the placenta.

Adult↗
PubMed1990

Double-blind test of human urinary macrophage colony-stimulating factor for allogeneic and syngeneic bone marrow transplantation: effectiveness of treatment and 2-year follow-up for relapse of leukaemia.

A randomized, double-blind placebo-controlled phase III clinical trial was performed to study the effects of human urinary macrophage colony-stimulating factor (hM-CSF) after allogeneic and syngeneic bone marrow transplantation (BMT) in 60 hM-CSF treated and 59 placebo control patients. HM-CSF was administered at a daily dose of 2 x 10(5) units/kg from day 1 to day 14 after BMT. Significant differences between hM-CSF and control patient were found in the recovery time to greater than 0.5 x 10(9) granulocytes/l and the survival rate during the initial 120 d without retransplantation. There was no difference in the incidence or grade of graft-versus-host disease (GVHD). There was no difference in the rate of leukaemic relapse at 24-36 months after BMT in patients with acute lymphocytic, acute nonlymphocytic, or monocytic leukaemia. The results of this trial show that human M-CSF improves the outcome of BMT without any influence on the occurrence of leukaemic relapse or GVHD.

Adolescent↗
PubMed1990

[Therapeutic evaluation of combination therapy using C-425 and antibiotics in severe bacterial infections--a double blind group comparative study. The C-425 Research Group for Infectious Comparative Study].

Clinical usefulness of C-425, a native human immunoglobulin liquid preparation for intravenous injection, was studied in combination with antibiotics in severe bacterial infections in a double blind group comparison using an alkylated human immunoglobulin liquid preparation (Polyglobin, A.gamma G) as a reference drug. The following results were obtained: 1. C-425 or A.gamma G was administered to a total of 117 patients, of whom 89 patients, 45 in C-425 group and 44 in A.gamma G group, were included in the present analysis of efficacy and usefulness. Analysis of safety of the drugs included a total of 113 patients, 58 in C-425 group and 55 in A.gamma G group. 2. Efficacy and usefulness were graded according to a visual analog scale (VAS). 3. Mean efficacy values with standard deviations of VAS value were calculated at 52.0 +/- 34.9 for the C-425 group, and 47.2 +/- 34.8 for the A.gamma G group. The respective medians were 59.0 and 61.0. The Mann-Whitney U-test revealed no significant differences between the two groups. When those with VAS values of 50 or above were regarded as cases of effective treatment, the efficacy rates of the two groups were also practically comparable. 4. Side effects were not observed in either drug group. 5. Mean usefulness values with standard deviations were 52.3 +/- 34.9 for the C-425 group, and 47.9 +/- 35.0 for the A.gamma G group. The respective medians were 60.0 and 61.0. The Mann-Whitney U-test revealed no significant differences between the two groups. When the cases with VAS values of 50 or above were regarded as cases of useful treatment, there were no significant differences in the utility rates between the two groups. From these results, C-425 was considered to be useful for treating severe bacterial infections when used combined with antibiotics.

Adolescent↗
PubMed1990

Extension of the substrate spectrum by an amino acid substitution at residue 219 in the Citrobacter freundii cephalosporinase.

The cephalosporinase of Citrobacter freundii GN346 is a class C beta-lactamase, consisting of 361 amino acids and exhibiting the substrate profile of a typical cephalosporinase. On the conversion of a conserved glutamic acid at residue 219 to lysine, the substrate spectrum of the cephalosporinase was extended to oxyimino cephalosporins, aztreonam and carbenicillin, which are essentially undesirable substrates for the enzyme. Escherichia coli cells carrying the mutant gene showed higher resistance levels to cefuroxime, aztreonam, and carbenicillin, but a lower resistance level to cefoxitin, than cells carrying the wild gene. The kcat values of the purified mutant enzyme for ceftazidime, cefuroxime, and cefmenoxime were 77,100, and 300 times those of the wild enzyme, respectively. The relative Vmax values of the mutant enzyme for aztreonam and carbenicillin were determined to be 11 and 23 times those of the wild enzyme, respectively, but the value of the mutant enzyme for cefoxitin was only one-third that of the wild enzyme.

Base Sequence↗
PubMed1990

An early phase II study of CPT-11: a new derivative of camptothecin, for the treatment of leukemia and lymphoma.

An early phase II study of a new camptothecin analog and an inhibitor of topoisomerase I, CPT-11, was conducted in 62 patients with refractory leukemia and lymphoma by four different treatment schedules in a multiinstitutional cooperative study. CPT-11 therapy resulted in four complete remissions (CRs) and three partial remissions (PRs) in 29 assessable non-Hodgkin's lymphoma (NHL) patients, one PR in three Hodgkin's disease (HD), one CR and one PR in 11 acute lymphoblastic leukemia (ALL), and one PR in 15 acute myelogenous leukemia (AML) patients. Single infusion of 200 mg/m2 every 3 to 4 weeks produced no response in both leukemia and lymphoma patients. Sixty-minute infusions of 40 mg/m2/d for 5 days every 3 to 4 weeks or for 3 days weekly produced four CRs (17%) and four PRs (17%) in 24 patients with malignant lymphoma. Sixty-minute infusions of 20 mg/m2 twice a day for 7 days every 3 to 4 weeks resulted in one CR and two PRs in 12 patients with acute leukemia. No response was seen in an acute leukemia patient by another treatment schedule. CPT-11 was effective in two (15%) of 13 primarily refractory leukemia and lymphoma cases, in two of four relapsed cases, and in seven (17%) of 41 relapsed and refractory cases. Major side effects were leukopenia (91%) and gastrointestinal (GI) (76%). CPT-11 was shown to be effective against refractory leukemia and lymphoma, and thus deserves further clinical study; the novel antitumor activity mode of this drug predicts no cross-resistance to presently available antitumor drugs.

Adolescent↗
PubMed1990

[Clinical evaluation of cefbuperazone in severe infections complicated with hematological disorders].

The efficacy and the safety of an antibiotic in cephamycin group, cefbuperazone (CBPZ), were investigated in 93 patients with severe infections complicated with hematological disorders. The efficacy evaluation was made in 85 cases with underlying hematological disorders including 49 cases (57.6%) of leukemia and 18 cases (21.2%) of malignant lymphoma. The overall efficacy rate was 50.6% of the 85 evaluable cases. The clinical efficacy rate for sepsis and suspected sepsis was 53.4%. The most frequently used group of antibiotics for combination therapy was aminoglycosides in 37 cases, in which an efficacy rate of 62.2%, a higher rate than the efficacy rate of 48.5% for all the combination therapy cases, was obtained. In 16 cases in which penicillins were used as combination drug, the efficacy rate obtained was low, 31.3%. Efficacy rates obtained for cases with different neutrophil counts at the start of therapies were as follows: 52.2% in 23 cases with neutrophil counts below 100/mm3, 46.2% in 13 cases with neutrophil counts between 100 and 499/mm3 and 51.3% in 39 cases with neutrophil counts equal to or above 500/mm3, thus no significant differences in efficacy rates were observed for patients with different neutrophil counts. These results appear to suggest that CBPZ, alone or in combination with other antibiotic such as aminoglycosides, may be quite useful in the treatment of severe infections in patients with hematological disorders.

Adolescent↗
PubMed1990

[Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate) on hematological malignancies].

Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate), a derivative of cytosine arabinoside, on hematological malignancies was conducted by multi-institutional cooperative group. YNK01 was administered orally at dose of 100-300 mg/body/day for more than 2 weeks. The number of registered and evaluated patients were 211 and 156, respectively. Of 23 patients with acute myelogeneous leukemia (AML), 2 complete response (CR), one partial response (PR) were observed (CR + PR: 13.0%). Hypoplastic leukemia (1/4: 25%), acute unclassified leukemia (1/1: 100%). Of 45 patients with MDS, 2CRs, 6 good response (GR) and 5PRs were observed (CR + PR: 28.9%). AML developing after a prior history of MDS (5/17: 29.4%), CML-BC (2/9: 22.2%). Of 19 patients with CML, 9 achieved CR, 3 achieved PR (63.2%). Of 11 patients with polycythemia vera, 4 achieved CR, 5 achieved PR (81.8%). Of 6 patients with essential thrombocytosis, 2 achieved CR, one achieved PR (50%). The major adverse effects included gastrointestinal toxicities such as nausea, vomiting, anorexia, diarrhea, and elevation of GOT and GPT which were tolerable and reversible. This study indicates that YNK01 is a useful agent against acute leukemia and MDS, especially RAEB, RAEB in T, CMMoL.

Acute Disease↗
PubMed1990

[Clinical evaluation of imipenem/cilastatin sodium in infectious complications of hematological malignancies. Tohkai Research Group on Infections in Hematological Disorders].

Imipenem/cilastatin sodium (IPM/CS), a newly developed carbapenem antibiotic, was administered to a total of 152 patients with severe infections complicating hematological disorders, of whom 138 patients are included in the present analysis of efficacy and 152 in that of safety. Most of the underlying diseases were acute leukemia (76/138), and most patients suffered from sepsis or suspicion of sepsis (84/138). Out of 138 patients in whom efficacy was evaluable, responses were excellent in 41 patients, good in 55, fair in 19, and poor in 23. The overall clinical efficacy rate was 69.6% (96/138). Prior antibiotic treatment and peripheral neutrophil count had significant effects on the clinical response. The overall eradication rate of bacteria was 76.2%. Adverse reactions were observed in 15 patients (9.9%) and abnormal laboratory test results in 19 patients (12.5%). From the above findings, IPM/CS is considered to be a useful antibiotic for the treatment of severe infections accompanying hematopoietic disorders.

Adolescent↗
PubMed1990

[Long-term surviving child with acute lymphoblastic leukemia complicated with legionellosis].

An 11 year-old girl was diagnosed as acute lymphoblastic leukemia (ALL) on November 26th 1979 and was induced into complete remission with vincristine and prednisolon. After consolidation therapy with daunomycin, vincristine and prednisolone, she developed pneumonia on January 21st 1980. No cause of pneumonia was found by sputum culture or serologic tests. Treatment with cefmetazol (CMZ), sulbenicillin (SBPC) and minocycline (MINO) was not effective but 9 g/day of LCM made a remarkable effect. Indirect immunofluorescence assay of antibody showed x 512 titers on January 22nd and in her recovery period, the titers showed eight times increased up to x 4,000. The diagnosis of Legionellosis was made on CDC's criteria. She recovered completely with sequential lincomycin (LCM) and erythromycin (EM) therapy. On October 1989, she is still in the first complete remission of ALL for more than 8 years.

Antineoplastic Combined Chemotherapy Protocols↗