[DIC: biochemical mechanism of hemostatic disorder].
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Biomedical subjects
Publications and source records attributed to K Deguchi.
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A 51-year-old women in menopause was admitted because of intermittent purpura. She was diagnosed as having cyclic thrombocytopenia. One platelet cycle lasted for about 22 days with platelet count fluctuating from 1.0 X 10(4)/microliters to 31.0 X 10(4)/microliters. The platelet-associated immunoglobulin was correlated with the platelet cycle. The rheumatic factor, antinuclear antibody, antimicrosome antibody, anti-thyroglobulin antibody and platelet binding immunoglobulin were all positive but did not fluctuate during the cycle. The platelet life-span was shortened. The mean platelet volume fluctuated during each cycle. The lipid emulsion test was prolonged. Symptoms of Sjögren syndrome and purpura appeared at the same time. It was strongly suggested that purpura was caused by cyclical destruction of platelets by reticuloendothelial system.
The hemostatic abnormality in 18 patients with adult T cell leukemia (ATL) was studied. Activated partial thromboplastin time (APTT) was slightly prolonged and prekallikrein activity was markedly low in these patients. The leukemic cell homogenate from these patients prolonged the recalcification time (RCT) of normal plasma; homogenates containing more than 3 x 10(3) cells/microliter prolonged it, although a lower cell concentration shortened it. The crude anticoagulant fraction from the gel filtration, with a molecular weight of about 34,000, prolonged RCT. The crude anticoagulant did not affect prothrombin time (PT), thrombin activity or activated X activity at any concentration, but prolonged the contact activation test, inhibited the activation of prekallikrein and prolonged RCT of Fletcher trait, Fitzgerald trait and F XII deficient plasma. These effects of ATL cell homogenate were stronger on platelet poor plasma than on platelet rich plasma. Although ATL cells had low procoagulant activity, increase of leukemic cells made anticoagulant activity predominant, might be the cause of hemostatic abnormality or amplify the bleeding tendency in patients with ATL.
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Dysfunction of vascular endothelial cells and accelerated calcification of the abdominal aorta were found in patients on maintenance hemodialysis. Indicators of vascular wall function, expressed as the amount of plasminogen activator and von Willebrand factor released during venous occlusion, suggested that the cubital venous wall in patients has normo- or hyper-responsiveness to occlusion. Calcification of the abdominal aorta on CT scan image was observed in most of patients including those of the ages of twenties years. The mean aortic calcification index (ACI), as an indicator of organic changes in vascular wall, was significantly higher in dialysis patients than in the nondialysis subjects. However, the mean values of indicators for vascular wall function decreased and ACI increased, as the period of treatment with hemodialysis became longer. A significant negative correlation was found between the mean ACI and most indicators of vascular wall function. The function of cubital vein was suggested to decrease in association with the progress in mural calcification of the abdominal aorta. We conclude that the alteration of the coagulation-fibrinolysis system induced by repeated hemodialysis may result from and continue to exacerbate endothelial damage, the consequence of which may be atherosclerosis.
Platelets were found to provide a surface for activation of plasminogen by the tissue-type plasminogen activator (t-PA) at an optimum concentration and to potentiate the generation of plasmin by the amidolytic method, fibrin lysis time and fibrin plate method. The effect of platelets on amidolytic activity on S-2251 was due to the potentiating effect of plasminogen activation by t-PA, because it was observed only in the presence of both plasminogen and t-PA. Plasmin generation was also evidenced in the SDS-PAGE profile of the supernatant from a mixture containing t-PA and plasminogen with platelets. These findings suggests that the potentiating activity of platelets on plasminogen activation by t-PA in circulation is one of the causes of fibrinogenolysis during fibrinolytic therapy with a high dose of t-PA. Platelets from patients with various diseases showed different potentiating activity on plasminogen activation by t-PA. The assay of this ability of platelets may be a new tool for evaluating their role in the blood fibrinolytic process.
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A case of carcinoid syndrome is presented. Pulmonary adenosquamous carcinoma with hepatic metastasis was found in a 60-year-old Japanese male who was complaining of fever, cough and haemosputum. After the treatment with 5-fluorouracil (5-FU) over 2 years, he was diagnosed as carcinoid syndrome on the appearance of facial flushing, face edema and watery diarrhea accompanied by high levels of 5-hydroxyindole acetic acid (5-HIAA) in blood and urine. Prednisolone, which was initially effective, was replaced by SMS201-995 due to the considerable dose increase of the former because its effect became insufficient during the course of the treatment. Clinical symptoms were improved by SMS201-995 and blood 5-HIAA level decreased gradually but markedly. Thus better results were obtained by SMS201-995 compared with prednisolone. These results imply that SMS201-995 is appreciated as an effective drug for treatment of carcinoid syndrome.
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Flomoxef (FMOX) has a broad antibacterial spectrum against Gram-positive and Gram-negative bacteria; especially its potent antibacterial activity against Staphylococcus aureus is a significant advantage that may not be found with other cephem compounds. In our determination of its antibacterial potency against various clinical isolates obtained from clinical materials (amniotic fluid, intrauterine secretions, exudates of the pelvic dead space) of patients with various infections, we obtained results representing specific features of this drug. From the results, the drug may be expected to produce an excellent effect in the treatment of various infections. Our study on drug concentrations in body fluids and genital tissues demonstrated a good transfer of this drug into various tissues; in every tissue examined, the drug administered by the usual method in the usual dose yielded a concentration exceeding MIC for principal pathogens, thus promising a good clinical response. Indeed a high clinical efficacy rate of 90.1% (good to very good responses) was obtained in a clinical trial involving 222 cases. Administration of the drug in 2 g quantity daily produced a high response rate of 92.8%. It was especially noteworthy that a good response was obtained in 30 of 32 cases (93.8%) in which other cephem compounds had failed. In evaluation of the bacteriological effect, furthermore, the drug showed an excellent rate of bacterial elimination. In conclusion, this drug is expected to be greatly useful in the light of its good transfer into genital tissues and its strong antibacterial activities against Gram-positive cocci, Gram-negative bacteria and anaerobes as well as against multiple bacterial infections predominating among women with genital infections.
Antibacterial activities of monobactam antibiotics (carumonam (CRMN) and aztreonam (AZT] against Gram-negative bacilli isolated from inpatients in the latter half of 1987 were investigated using penicillin (PC: piperacillin (PIPC], cephems (CEPs: ceftazidime (CAZ), cefotaxime (CTX), latamoxef (LMOX), cefsulodin (CFS], carbapenem (imipenem (IPM] and pyridonecarboxylic acids (norfloxacin (NFLX) and ofloxacin (OFLX] as reference antibiotics. A total of 400 strains of 13 species, i.e. Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Citrobacter freundii, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Pseudomonas aeruginosa and Haemophilus influenzae, were used as test strains. 1. CRMN and AZT, both monobactam antibiotics, were roughly comparable in their activities and no resistant strain to these antibiotics were found among isolates of E. coli, Klebsiella spp., Proteus spp., M. morganii, P. rettgeri or H. influenzae and few resistant strains were observed among isolates of S. marcescens. On the other hand, isolates of C. freundii, Enterobacter spp. and P. aeruginosa included rather numerous strains resistant to the monobactam antibiotics. Among these cases, whereas R strains, i.e. resistant strains showing MICs greater than or equal to 50 micrograms/ml, accounted for a large proportion of strains resistant to PC and CEPs, I strains, i.e. intermediately resistant strains showing MICs between 12.5 and 25 micrograms/ml, accounted for a large proportion of strains resistant to the monobactam antibiotics. 2. Strains resistant to PIPC, a PC, were detected with high and more or less uniform frequencies over the entire spectrum of the isolates examined. 3. Antibacterial activities of CEPs varied against different bacterial species. While strains resistant to CTX, CAZ and LMOX were commonly detected with high frequencies among isolates of C. freundii, Enterobacter spp. and S. marcescens, large percentages of LMOX-resistant strains of C. freundii and Enterobacter spp. were of the I type. CTX-resistant strains were also found among isolates of P. vulgaris and M. morganii. Proportions of CEP-resistant strains of P. aeruginosa were 28% for CFS and 12% for CAZ. 4. No or few strains among the isolates of 13 species investigated were resistant to IPM, a carbapenem antibiotic, which showed the most stable antibacterial activity, but it was less active than monobactam antibiotics and CEPs against Klebsiella spp., P. mirabilis and H. influenzae.(ABSTRACT TRUNCATED AT 400 WORDS)
Antibacterial activity of gentamicin (GM), along with activities of other aminoglycosides and beta-lactams, was studied against clinical isolates collected from pediatric patients during a period of May 1986-April 1987. 1. GM-resistance was noted in 22% of Staphylococcus aureus, 6% of Proteus vulgaris, 8% of Morganella morganii, 40% of Providencia spp., 6% of Enterobacter spp., 14% of Serratia marcescens, and 14% of Pseudomonas aeruginosa isolates. No GM-resistance was observed with isolates of Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis. 2. The antibacterial activity of GM against clinical isolates from pediatric patients was found to be comparable to its activity against clinical isolates from adults studied at the same time. 3. The majority of GM-resistant strains of S. aureus were MCRSA, and the GM-resistant strains of S. marcescens and P. aeruginosa were found also to be resistant to multiple drugs. 4. GM-resistant strains were found at relatively high rates (14-22%) in S. aureus, S. marcescens and P. aeruginosa. These rates did not increase compared to the rates observed in the first half of the 1980's. 5. GM was considered to have poor antibacterial activity against genus Providencia. It is concluded from above results that GM still maintains effective antibacterial activity against many of causative organisms of infections in both adults and children.
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Sultamicillin (SBTPC) is a mutual prodrug in which ampicillin (ABPC) and a potent beta-lactamase inhibitor sulbactam (SBT) are ester-bound in an equimolar ratio. SBTPC is hydrolyzed during absorption after oral administration to provide ABPC and SBT for systemic circulation. In the present study, the antimicrobial activities of SBTPC against 50 isolates each of 6 species (Staphylococcus aureus, Klebsiella pneumoniae subsp. pneumoniae, Branhamella catarrhalis, Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus pyogenes) of bacteria freshly obtained from upper respiratory tract infections were examined in relation to their bacterial beta-lactamase producing abilities. beta-Lactamase producing strains were identified using the acidometry disc method with benzylpenicillin (PCG) of cefazolin (CEZ) as a substrate, and their frequencies of appearance were calculated as follows: S. aureus 86%; K. pneumoniae subsp. pneumoniae 100%; B. catarrhalis 68%; H. influenzae 24%. Fourteen per cent of S. aureus strains examined were beta-lactamase positive using both PCG and CEZ acidometry discs. SBTPC, however, demonstrated excellent antimicrobial activities even against these beta-lactamase producing strains. Good activities were observed especially against those bacterial strains producing penicillinase (PCase). Average MIC80 values of SBTPC were 3.13 micrograms/ml for S. aureus and K. pneumoniae subsp. pneumoniae, 0.39 micrograms/ml for B. catarrhalis and H. influenzae, 0.05 micrograms/ml for S. pneumoniae and 0.025 micrograms/ml for S. pyogenes. As SBTPC was shown to possess excellent antimicrobial activities against PCase producing strains, the enhancement in activities of SBTPC compared to ABPC alone can be attributed to the inhibition of beta-lactamase by SBT which, as noted above, is a component of SBTPC in an equimolar ratio to ABPC.
In an attempt to examine the effect of sulbactam (SBT) on beta-lactamase activity, three hundred clinical isolates from the infected upper respiratory tract were tested for MICs and disk sensitivities of ampicillin (ABPC) and sultamicillin (SBTPC). beta-lactamase production was tested using the acidometry disk method (beta-Check, Taito Pfizer Co.). For strains such as Klebsiella spp. which form mucoid type colonies, we used the SS culture medium which, by reducing the influence of huge amounts of capsular material, allows a better reaction to the acidometry disk. Penicillinase, produced by Branhamella catarrhalis, Haemophilus influenzae, Neisseria spp., etc. was detected clearly by direct application of portions of colonies onto acidometry disks. For cephalosporinase, however, a direct application of such fractions resulted in weak reactions. We, therefore, used fractions which had undergone the enzyme induction, and obtained better reactions. Sensitivities of tested bacteria to ABPC and SBTPC were inversely related to MIC values. beta-Lactamase-producing strains showed weaker sensitivity to ABPC than non-producing strains. To SBTPC, however, beta-lactamase-producing strains and non-producing strains showed very similar sensitivity. We thus confirmed that the inhibitory action of SBT to beta-lactamase can well be demonstrated using the disk sensitivity method.