[Oral administration of etoposide therapy in refractory malignant lymphoma and adult T cell lymphoma].
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Biomedical subjects
Publications and source records attributed to Y Imamura.
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Befunolol (BF) reductase with 3 alpha-hydroxysteroid dehydrogenase activity, which was purified from rabbit liver, catalyzed the oxidoreduction of prostaglandins, indicating that this enzyme has broad substrate specificities for endogenous substances. BF reductase was strongly inhibited by a variety of nonsteridal anti-inflammatory drugs and then a significant correlation was observed between the logarithms of IC50 (concentration required to produce 50% inhibition of BF reductase activity) values and the maximal daily human doses for nonsteroidal anti-inflammatory drugs. These results suggest that the pharmacological potency of nonsteroidal anti-inflammatory drugs may be predicted from the degree of inhibition of BF reductase by these drugs.
Highly methicillin-resistant Staphylococcus aureus (H-MRSA, MIC greater than 100 micrograms/ml) was prevalent from 1986 in our institution. The failure of povidone-iodine to reduce the prevalence of MRSA led us to choose chlorhexidine-ethanol solution as an antiseptic, and then the isolation frequency of H-MRSA decreased significantly in 1988. When H-MRSA began to increase again recently, we studied the resistance to antiseptics of MRSA in order to investigate the cause of this re-increase. Common antiseptics were tested against 45 strains of H-MRSA and 22 strains of methicillin sensitive S. aureus (MSSA, MIC less than 12.5 micrograms/ml). Dilute preparations (1:100) of povidone-iodine and chlorhexidine-ethanol solution were more effective on H-MRSA than the other antiseptics. Though there was no significant difference between H-MRSA and MSSA in their sensitivity to povidone-iodine, the killing of H-MRSA strains was more delayed than the killing of MSSA strains in chlorhexidine. Even after a 120-second exposure, 13.3% of H-MRSA strains were resistant to chlorhexidine (more than 1000 colonies were recovered). These highly chlorhexidine-resistant strains have been isolated since 1987 when we chose chlorhexidine-ethanol solution as the antiseptic in our institution. Therefore we suspect that the acquirement of resistance to antiseptics by H-MRSA caused the re-increase of this strain.
We evaluated 10 patients with verified brachial plexus injuries and root avulsion. In 100%, dermatomal somatosensory evoked potentials (DSSEPs) were abnormal. Compound muscle action potentials (CMAPs) by magnetic stimulation revealed 90% abnormal findings on the affected side, but also revealed abnormality in adjacent segments. Dissociation of CMAPs and DSSEPs revealed the apparent continuity of motor and sensory nerves. The use of both techniques for the examination of the function of proximal peripheral nerve revealed increased latencies over the motor and/or sensory pathways in all patients. The technique of non-invasive stimulation of the motor pathway therefore provides an additional tools to detect and quantify subclinical and clinically apparent lesions in patients with defined brachial plexus injuries and root avulsions.
We studied the endoscopic features in 6 cases of advanced gastric cancer responded to chemotherapy. Patient characteristics were as follows. [table; see text] Age 43-77 (mean 63 years old) Endoscopic type Mean duration of PR was 26.6 weeks. The process of the improvement of primary lesion as judged by endoscopic findings were as follows. Firstly getting flat of wall, secondly reduction in size of ulcer, and lastly changing into scar. Number of reported cases including our case No. 6 which are diagnosed as scar endoscopically after chemotherapy and are operated successfully has been increasing. Most of them showed scar macroscopically with wide and irregular surface. Especially our case No. 6 showed keloidal scar. In these cases, the histological improvement into grade 2-3 was observed in scared tissue. Sooner or later, such a process of endoscopic improvement was observed 4-8 weeks after initiation of chemotherapy. Unless the endoscopic improvement was observed 8 weeks after initiation, regimen of chemotherapy should be changed into others.
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We determined the activities of urea cycle enzymes in the liver of C3H-H-2 degree-jsv mice. The activities of all urea cycle enzymes decreased in the latter period of lactation. The activities of carbamylphosphate synthetase and ornithine transcarbamylase in some affected mice were undetectable. On the other hand, the activities of enzymes other than urea cycle enzymes were normal. We consider that the decrease in the urea cycle enzymes is caused by an abnormality in the mechanism of gene expression.
In precancerous states or early cancer, the serum levels of tumor markers are almost not detectable. Therefore, the tissue contents of CEA and CA19-9 were measured in 48 colonic polyps, 8 colorectal cancers and 5 normal colonic mucosa. These tissue specimens were obtained by endoscopic polypectomy, surgery or autopsy, and homogenated in normal saline (10 ml/wet g of tissue). After centrifugation, the supernatant was assayed by enzyme or radioimmunoassay. There was no correlation between serum levels and tissue contents of CEA or CA19-9 in colonic adenomas and colorectal cancers. The mean contents of tissue CEA and CA19-9 in colonic polyp and colorectal cancer were significantly higher than normal colonic mucosa, and the highest contents of CEA and CA19-9 were found in colorectal cancer. The contents of tissue CEA and CA19-9 in cancerous regions were markedly increased as compared with noncancerous regions. In adenomas, there was a relationship between the degree of histological dysplasia and the tissue content of CEA. Relationships were also found between macroscopic findings and tissue tumor markers in adenomas. These results suggest the possibility that the measurement of tissue tumor markers may be useful for borderline colonic lesions.
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The interaction of acetohexamide (AH) with phenylbutazone (PBZ) was investigated in rabbits. Orally administered PBZ caused a potentiation of hypoglycaemic action after oral administration of AH. This can be explained by the fact that the co-administration of PBZ significantly increased both the serum concentrations of AH and its pharmacologically active metabolite. (-)-hydroxyhexamide [(-)-HH], after AH administration. The co-administration of PBZ decreased the renal clearance (Clr) and non-renal clearance (Clnr) of AH. PBZ inhibited the in vitro reduction of AH to (-)-HH and decreased the accumulation of (-)-HH by the kidney cortical slices. These results indicate that the mechanism of in vivo interaction of AH with PBZ is complicated.
Intravenously co-administered ketoprofen decreased the plasma concentration of sulpha-dimethoxine (SDM) after intravenous bolus administration to fast acetylator rabbits, and significantly increased the total body clearance (CLtot) and steady-state volume of distribution (Vdss) of SDM. On the other hand, ketoprofen had little effect on the plasma concentration of SDM in slow acetylator rabbits. When SDM was intravenously administered in combination with ketoprofen, an increase in the plasma concentration of N4-acetylsulphadimethoxine, a major metabolite of SDM that strongly displaces SDM from its binding sites, was observed in all rabbits, but the increase was much larger in fast acetylators. We conclude that the acetylation capacity for SDM is a factor determining the pharmacokinetic interaction between SDM and ketoprofen in rabbits.
The kinetic mechanism for the reduction of befunolol catalyzed by befunolol reductase from rabbit liver was investigated. From the initial velocity analysis, product inhibition and coenzyme binding studies, the reduction of befunolol was found to proceed through an ordered Bi Bi mechanism, in which beta-nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) binds to the enzyme firstly and NADP+ leaves lastly. NADPH bound to the free enzyme at a molar ratio of 1:1. Furthermore, the result of dead-end inhibition by Cibacron blue F3GA, a nucleotide analogue which binds to many enzymes, was consistent with the ordered Bi Bi mechanism for the enzyme.
Concomitant with the extensive use of antibiotics, the number of multiple antibiotic-resistant strains has been increasing. Since resistance is mainly mediated by R plasmids, we undertook to investigate the characteristics of R plasmid-determined beta-lactamase in 6 Gram-negative rods. The beta-lactamase produced by each organism was classified by its substrate: type P which attacks penicillins, type C which attacks cephalosporins, and type C/P which attacks both penicillins and cephalosporins. Though the chromosomally mediated beta-lactamase of almost all Gram-negative rods is classified as type C, R plasmid-mediated beta-lactamase is almost equally active against both penicillins and cephalosporins. Therefore, we suggest that type C/P beta-lactamase was mediated by R plasmids in Gram-negative rods which already produced chromosomally mediated type C beta-lactamase. The strains which produced type C/P beta-lactamase tended to be more resistant to antibiotics than the other beta-lactamase producing strains. Among type C/P strains, the sensitivity to cephalosporins varied with the bacterial species, whereas all these strains were highly resistant to penicillins. Even for piperacillin, which is stable to cephalosporinase, the MIC at which the cumulative percentage of strains inhibited was 50% (MIC50) was over 50 micrograms/ml in all strains tested.
Eighteen patients with progressive/locally recurrent cancer of the stomach were given therapy with MMC, ADM, CDDP, Etoposide (VP-16), and 5'DFUR (MAC-VD therapy). Drugs were administered intravenously with MMC 10 mg/m2, ADM 20 mg/m2, and CDDP 50 mg/m2 on day 1; orally with etoposide 100 mg/day for five consecutive days from day 3; and orally with 5'DFUR 600 mg/day for three weeks from day 3 followed by discontinuation for one subsequent week. This drug regimen was one course of the treatment and repeated as far as possible. There were 16 evaluable cases; the sex distribution was ten males and six females. Patients ranged in age from 43 to 78 years. P.S. 1 was two cases; 2 ten cases; and 3 four cases. The overall response rate, CR + PR, was 1 + 7/16 (50%), while this rate for primary disease was 2 + 5/16 (43.8%). Of the two CR cases, one primary lesion became operable and CR was demonstrated histologically. The overall response rates, CR + PR, for metastatic lesions were 1 + 3/9 (44.4%) for the liver; 0 + 1/4 (25.0%) for the abdominal lymph nodes; 0 + 1/2 (50.0%) for the superficial lymph nodes; 0 + 1/2 (50.0%) for the bones; and 0 + 1/1 (100%) for the lung. The median duration of the response was 3.7 months (range between 1.5 and 8.2+) and the median duration of survival 5.1+ months (range between 2.2+ and 13.3+). At the same time, the hematological side effects of both leukocytopenia and hypohemoglobinemia were seen in 43.8% of the cases. Non-hematological side effects included alopecia in 18.8% and nausea/vomiting in 12.5%. There was no case of discontinuation due to side effects. It was concluded that the therapy with MMC, ADM, CDDP, etoposide and 5'DFUR (MAC-VD therapy) proved to be a very promising drug regimen in the treatment of stomach cancer with high rates of response and is expected to be a step forward in the establishment of interdisciplinary treatment.
Twenty-five patients with advanced gastric cancer were treated with a combination chemotherapy. The levels of serum CEA, CA 19-9, TPA and CA 125 were measured before and during chemotherapy (4 and 8 weeks). One complete and 10 partial responses were obtained, and the response rate was 44%. Pretreatment positive rates of these four tumor markers were all more than 60%, and the positive rate of combination assay was 96%. The mean percent changes of these four tumor markers were similar and correlated well with the response to chemotherapy. There was a significant correlation between tumor reduction and decrease of serum CEA in the responders with measurable lesions. These results suggest that the measurement of changes of serum tumor markers may be useful for monitoring the response to chemotherapy in patients with gastric cancer. It also may be useful to determine early the effectiveness of the treatment.
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A 15-year-old man with food-dependent exercise-induced anaphylaxis is reported. The patient had begun to run 4 hours after he had lunch on fried shrimps. When running about 2000 m, he suffered from general cutaneous erythema with itching, urticaria, angioedema of face and dyspnea. He had experienced the similar episodes associated with postprandial exercise before. Skin test and IgE-RAST were positive for shrimp. Exercise challenge test after having 20 g boiled shrimp was conducted, and the elevation of plasma histamine level was recognised. 25 cases with food-dependent exercised-induced anaphylaxis have reported in Japan. 13 of 25 cases were related with wheat, and 10 cases were related with shrimp. 14 of 25 cases had experienced the similar episodes. Exercise as part of planned health program has virtually mushroom world-wide. Therefore, the fact that anaphylaxis can be a complication of such exercise must be recognised if appropriate prevention and treatment are to be administered.
A 22-year-old female was admitted to our hospital because of general fatigue. The lymph nodes, liver and spleen were not palpable. She was without cutaneous lesions. Haematological examinations revealed leukocytes 3,200/microliters with 44% blasts of myelomonocytic origin, and platelets 15,000/microliters. Bone marrow smears were hypercellular marrow with 51% blasts of myelomonocytic origin and focal involvement of mast cells. Serum histamine and vitamin B12 level was high. Mast cells were round with rounded or segmented nuclei. The nucleoli were inconspicuous and the cytoplasm contained a number of metachromatic granules. Cytochemically, mast cells stained positive for alpha-naphthol-AS.D-chloroacetate esterase and acid phosphatase, and negative for peroxidase, Sudan black B and alpha-naphthyl butylate esterase. In toluidine blue staining, mast cells had stained similarly with pH values from 2.5 to 6.5. She was diagnosed as acute myelomonocytic leukemia with benign mastocytosis, and treated with BH.AC-DNP. A complete remission was obtained, but mast cells in the marrow did not decrease. Relationship between leukemia and mastocytosis was not known, but it was suggested that mast cells responded to the proliferation of the leukemic cells.