Biomedical subjects
Publications and source records attributed to Y Mitomo.
A relationship between the survival time and T cell subsets in the chronic phase of chronic myelogenous leukemia (CML) studied by the method using monoclonal antibodies. No statistic difference between normal and CML was recognized in the rate of pan-T cell. The high T-Helper/Suppressor ratio (TH/TS) was revealed in the cases of the long survival time for more than six years.
Ceftriaxone (CTRX), a new long acting antibiotic in the 3rd generation cephem group, was administered intravenously once or twice a day in daily doses of 1-6 g for at least 3 days to 86 patients with severe infections complicating hematopoietic disorders. Underlying diseases were acute leukemia in 41 cases, chronic leukemia in 3 cases, malignant lymphoma in 19 cases, myeloma in 7 cases and others. Most patients (55 cases) suffered from sepsis or suspected sepsis. As for efficacy rates classified by underlying diseases, the treatment was effective in 61.0% of patients with acute leukemia. As for efficacy rates classified by infections, the treatment was effective in 60.0% of patients with sepsis. No side effects were noted except rash in 2 patients. Abnormal hepatic functions were recognized in 3 patients but were not attributed to the agent in any case. The results indicate that CTRX is a safe and useful antibiotic for the treatment of severe infections accompanied by hematopoietic disorders.
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A phase II study of carboplatin for malignant lymphoma was conducted. Thirty-nine patients with malignant lymphoma were entered into this study, and 6 of them were excluded from evaluation due to violation of selection criteria. The remaining 33 cases were studied to assess the effectiveness and safety of this drug. Two CR and 11 PR were obtained with this medication (effective rate 39%). The significant affecting factors were previous treatment, disease stage and P.S. score. Many cases suffered from gastrointestinal symptoms and reduced hematopoiesis. The former complication was self-limited without any fatal episodes. However, the latter included severe cases, especially thrombocytopenia, which is suggested to be a dose limiting factor (DLF) of this drug.
The effect of antitumor agents on the cell cycle traverse of cultured FL cells, a monolayer culture line derived from human amnion, was investigated by flow cytometry (FCM) in combination with simultaneous determination of total cell number, viability, mitotic index and labeling index by [3H]TdR. The results obtained can be summarized as follows: Antimetabolites prolonged the duration of the S phase at a low dose, while at a high dose they decreased the rate of progression from the G1 to S phase, resulting in G1 and G1-S boundary accumulation. Partial synchronization by these agents was obtained through two different mechanisms. In vinca alkaloid-accumulated cells in the G2+M phase at 24h, mitotic index (MI) reached 20%, which was 10 to 20 times higher than that of control and most M-phase cells, which consisted of metaphase cells. Other cells in a tetraploid state were considered to be in the G2 phase or possibly G1 phase of the tetraploid cycle. Antibiotics generally accumulated cells in the G2 phase, but agents could be divided into two groups according to the degree of G2 accumulation. One group showed almost complete G2 accumulation, while the other showed only partial accumulation. The former group inhibited the progression of the S phase at a higher dose. Both groups completely inhibited the progression of the cell cycle at the highest dose. Alkylating agents only partially accumulated cells in the G2 phase at a low dose, showed prolongation of the S phase at a high dose, and inhibited the progression of the cell cycle at the highest dose, as with antibiotics. On the basis of these results, the application of these agents for treatment of cancer, especially leukemia, is discussed from a rational viewpoint.
A phase II study of the oral agent methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU tablet) for myeloproliferative disorders was performed. Fifty-two patients were treated with MCNU tablets and 43 patients were evaluated for clinical effects and 45 for adverse effects. The standard regimen was as follows; oral administration of 50mg (one tablet)/body/day every 4-6 days was considered as one course, and this was repeated at 6-8-week intervals if possible, with certain modifications according to dosage, period of administration and dose interval wherever necessary. Of 16 patients with chronic myelogenous leukemia (CML) in the chronic phase, 13 achieved complete remission (CR), and 3 achieved partial remission (PR). The overall response ratio was 100%. Rapid reduction of leucocytes was detected within two weeks. One patient with CML in blast crisis achieved PR (100%). Of 15 patients with polycythemia vera, 13 showed an excellent effect (87%), and 1 a moderate effect (6.7%), the overall response ratio being 93%. In essential thrombocythemia, an excellent effect (70%) was obtained in 7 of 10 patients. One patient with myelofibrosis showed an excellent effect (100%). Nausea & vomiting (33%) and anorexia (13%) were major adverse effects, but these symptoms were observed only transiently. Liver dysfunction was also seen in 8.9% of patients, but no patient showed severe manifestations. Our study supports the contention that MCNU tablet is a useful agent against myeloproliferative disorders.
N4-Palmitoyl-1-beta-D-arabinofuranosylcytosine (PLAC) was administered PO to 76 patients with acute leukemia, myelodysplastic syndromes (MDSs), and myeloproliferative disorders (MPDs). Of 20 patients with acute myelogenous leukemia, 2 achieved complete remission, and the only patient with acute lymphoblastic leukemia achieved partial remission. Remission was reached with PLAC 100-300 mg/day 25-66 days after the start of therapy. Among 22 patients with MDS, 1 patient achieved a good response and 8 achieved partial response. Responses were reached with PLAC 50-200 mg/day 7-153 days (median, 33 days) after the start of therapy. Improvement of polycythemia was observed in all 5 patients with polycythemia vera, and reduction of thrombocytosis was observed in 5 out of 6 patients with essential thrombocythemia and myelofibrosis. An antileukemia effect was noted in 1 of 5 with chronic myelogenous leukemia. Major side effects were gastrointestinal toxicities and myelosuppression. In spite of the disadvantages, such as unpredictable absorption and a lower response rate to acute leukemia compared with its parent compound, this antileukemia Ara-C analogue that is administrable PO will be useful in the treatment of MDSs and MPDs, which do not necessarily require admission to hospital, and in the treatment of acute leukemia of the aged, a condition for which intensive chemotherapy is not appropriate.
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A 59-year-old male was admitted to our hospital with complaints of general fatigue, abdominal distension and edema in the legs in February, 1985. Laboratory findings were as follows: GOT 152 IU/l, GPT 129 IU/l, LDH 555 IU/l, ALP 1147 IU/l, gamma-GTP 413 IU/l, T.-Bil 2.1 mg/dl and AFP 422.6 ng/ml. Multiple SOLs were recognized in both lobes of the liver by abdominal CT scan and echography. Interferon-gamma (gamma-IFN: KW-2202; Kyowa Hakko Co.) therapy was started in March from an initial dose of 1 X 10(6) units and was increased up to 4 X 10(6) units, 2 X 10(6) units being administered as a maintenance therapy for 12 weeks. The tumors became remarkably smaller in size, AFP was decreased to 38.8 ng/ml, and PR was obtained. The only side effect was temporary fever. The patient was subsequently followed without gamma-IFN at an outpatient clinic for about 100 days, but finally died due to rupture of esophageal varices and hepatic failure.
Infected patients with hematological disorders were treated with the combination of cefmenoxime (CMX) and cefsulodin (CFS). This therapy was done on 74 patients, of whom 38 (51%) had acute myelocytic leukemia, 14 (19%) malignant lymphoma, 7 (9%) acute lymphocytic leukemia, 5 aplastic anemia, 4 adult T cell leukemia, 4 chronic myelocytic leukemia, 1 multiple myeloma and 1 histiocytic medullary reticulosis. Complicated infections included 5 cases of septicemia, 41 cases of suspected septicemia, 19 cases of respiratory tract infection, 2 with anal abscess, 1 with urinary tract infection and others. The obtained results were as follows: Clinical effectiveness of the combination therapy was excellent in 17 cases (23.0%), good in 24 (32.4%) and poor in 33 (44.6%). Total clinical efficacy rate was 55.4%. Clinical efficacy rate was 40% against septicemias, 51.2% against suspected septicemias and 57.9% against respiratory tract infections. Causative pathogens were isolated in only 21 cases (28.4%): Gram-positive bacteria in 9 cases, Gram-negative bacteria in 11 and fungus in 1. About half of the Gram-negative bacteria belonged to Pseudomonas sp. The efficacy rate of this combination therapy against Gram-negative bacterial infections was 72.7% but the rate against Gram-positive bacterial infections were only 33.3%. Only in 1 case, this combination therapy was discontinued because of drug eruption. Abnormal laboratory findings were observed in 5 cases: Elevation of BUN in 3, GOT and GPT in 1 and prolongation of activated partial thromboplastin time in 1. In conclusion, this combination therapy of CMX and CFS is useful and safe against infections complicated by hematological disorders.
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Sixty-three infectious episodes in 61 patients with hematological disorders were treated with cefminox (CMNX, MT-141), a new antibiotics in the cephamycin group. CMNX was given by 1 hour infusion every 8 to 12 hours in a dose of 4 to approximately 6 g per day for 3 to 12 days, not being combined with other antibiotics. CMNX was effective in 45% of total cases. In 24 cases, the number of granulocytes at the start of CMNX were less than 500/mm3, and 11 cases (46%) of them responded to CMNX. Thus, CMNX was found effective in severe infections in patients with hematological disorders. No serious side effects attributable to CMNX were noted.
The patient was a 50-year-old man. Chest X-ray films showed a tumor shadow near the heart, which was diagnosed as carcinoma of the left lung. The patient's heart suddenly and unexpectedly stopped and he consequently died when his body was set in the right lateral position for operation on the left pulmonary tumor. A tumor measuring 6 X 3 X 3 cm was found in the region from the right ventricle to the pulmonary artery at autopsy. It was postulated that the tumor might have obstructed the pulmonary artery when the position of the patient's body was changed for surgery. A metastatic nodule was found in the left lung. The tumor was a rhabdomyosarcoma, the pleomorphic type.
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Ceftizoxime (CZX) was given by intravenous injection in daily doses of 2-8 g to 103 patients with severe infections complicating hematopoietic disorders. The clinical effect was evaluated in 95 of the 103 patients. The causative organisms were identified in 22 patients but were unknown in the remaining 73. Infected sites were the respiratory tract, urinary tract, soft tissue, and blood. The overall effectiveness rate (inclusive of marked and moderate) was 61.1% (58/95). The effectiveness rate was 63.6% (14/22) in patients in whom the causative organisms were identified and 60.3% (44/73) in patients in whom the causative organisms could not be identified and 60.0% (18/30) in 30 patients with less than 100 neutrophils per mm3 before treatment. No side effects were noted except drug fever in 1 patient. Abnormal hepatic function was seen in 6 patients but was not attributed to the drug in any case. The results indicate that CZX is a safe and useful antibiotic for the treatment of severe infectious complications in hematopoietic disorders.
The esophagus was totally excised for histopathological examination in 276 autopsy cases and 66 surgical cases (total, 342 cases). Leiomyoma of the esophagus was observed in 27 of the 342 cases. The tumors were present in 22 of the 225 male cases and in 5 of the 117 female cases. There were 38 leiomyomas among the 27 cases. Most of the leiomyomas originated in the inner circular muscle. None of the tumors was more than 7 mm. in length. Twenty-five of the 38 leiomyomas were located in the esophagogastric junction zone. Thus, subserial histological examination revealed leiomyomas at a higher frequency than that in previous reports.