CHEMOTHERAPY
Online ISSN : 1884-5894
Print ISSN : 0009-3165
ISSN-L : 0009-3165
Volume 34, Issue 8
Displaying 1-11 of 11 articles from this issue
  • HISASHI Aso, TAKUSABURO EBINA, NAKAO ISHIDA, FUJIO SUZUKI
    1986 Volume 34 Issue 8 Pages 665-671
    Published: August 25, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Ge-132 [Carboxyethylgermanium sesquioxide; O3 (GeCH2CH2COOH) 2], an organogermanium compound, has been shown to have antitumor activities in mice and rats, as revealed by inhibition of tumor growth in and prolongation of survival period of these animals. It has also been proved to have, in both human and mice, immunopotentiating activities, through both the induction of interferon-γ in serum and the augmentation of natural killer (NK) cell activity. On the basis of these observations, we study in this paper the effects of Ge-132 on influenza virus infection in mice. When DDI mice were infected with 10 LD50 of influenza A2 (H2N2) virus by inhalation, administration of 20mg/kg or 100mg/kg of Ge-132 for 6 consecutive days starting on the day of infection was found to have a significant protective effect. An increase in the survival fraction, a prolongation of the mean length of survival, an inhibition of the development of lung consolidation, and a decrease in virus titers in the lungs were found in treated groups as compared to control which was given PBS. NK activity in the spleens and lungs of the virus-infected mice was also significantly augmented by orally given Ge-132. In addition, NK cells whose activity was augmented by Ge-132 in vivo revealed a definite killing activity towards NK-insensitive Meth-A cells when the latter were sensitized with influenza virus in vitro. Nevertheless, no direct virocidal or virostatic activities of Ge-132 on the influenza virus were ever found in vitro.
    These results indicate that the protective effect of Ge-132 against influenza virus infection in mice seems to be explained by its IFN-γ inducing activity and in particular through its augmentation of NK cells.
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  • ANTIMICROBIAL SUSCEPTIBILITY TO NEW β-LACTAM ANTIBIOTICS AND PATHOGENICITY IN MICE
    MUNEO HIKIDA, SUSUMU MITSUHASHI, MATSUHISA INOUE, TAKASHI INAMATSU, KY ...
    1986 Volume 34 Issue 8 Pages 672-676
    Published: August 25, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Ninety-six Staphylococcus aureus strains were isolated from septicemic patients at the Tokyo Metropolitan Geriatric Hospital and their in vitro antimicrobial susceptibility to 9 β-lactam antibiotics was examined. Twenty-five% of the isolates were not inhibited by methicillin at a concentration of 6.25μg/ml. All of these methicillin-resistant strains possessed inducible penicillinase activity.
    Most drugs showed strong antibacterial activity against 96 S. aureus strains. Especially, imipenem was found to be most active and was followed by cephaloridine, SCH 34343, L-105, and HR 810, in that order.
    Pathogenicity of these strains toward mice was examined, indicating that there were no Smith-like strains possessing high pathogenic to mice among the isolates. Especially, it was found that the highly methicillin-resistant (≥200μg/ml) strains didn't show any pathogenicity toward mice, when infected with saline suspension (O.5 ml) of 108 cells/ml of these strains.
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  • YOSHIKI OBANA, HIDEO KITAGAWA, RURIKO NAKA, KAZUSHIGE TANAKA, TAKESHI ...
    1986 Volume 34 Issue 8 Pages 677-681
    Published: August 25, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    An experimental uterine infection model was prepared in mice using Escherichia coli strain 444.
    The uterine infection was distinctly caused by E. coli in five-week-old female mice untreated withprogesterone, The induction of uterine infection with this organism was possible by the inoculation of ca. 105 cells per mouse or more. This infection model continued for at least 7 days, but did notturn into sepsis.
    Against the uterine infection produced by E. coli, the corresponding therapeutic efficacy to the dose of ofloxacin and ciprofloxacin were observed.
    Thus, the preparation of uterine infection caused by E. coli was successful. It seemed that thismodel can utilize as one of the in-vivo evaluation model to antibiotics.
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  • COMPARATIVE ANALYTICAL STUDIES OF THERAPEUTIC EFFECTS OF ANTIBIOTICS ADMINISTERED IN MICE OF DIFFERENT STRAINS
    MASATOSHI OGAWA, KENJI KAWASAKI, SACHIKO GOTO
    1986 Volume 34 Issue 8 Pages 682-687
    Published: August 25, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Comparative studies were made on mice of ddN and ICR strains on the therapeutic effect of antibiotics administered.
    MLD of Escherichia coli C 11 inoculated intraperitoneally was smaller in ICR strains, representing higher susceptibility and the same results were observed in experimental infection with strains of Serratia marcescens and Pseudomonas aeruginosa.
    ED50 values of ampicillin, carbenicillin, sulbenicillin, cefazolin, gentamicin and dibekacin obtained in ICR strains were generally smaller than those in ddN strains against the same infectious dose of E. coli C11.
    Pharmacological examination revealed that, in contrast with normal mice, a higher serum level of antibiotic was attained in infected mice of ICR strain.
    The above results indicate that, in assessing the in vivo antibacterial effect accurately, pharmacological properties of antibiotics in infected mice should be investigated with the same strain as was used for efficacy tests.
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  • RELATION BETWEEN FIC INDEX AND CLINICAL EFFICACY
    RUEY-MEI CHEN, NORIO KIKUCHI, NORIKO MURAKI, KEIICHI NAGAO, TAKAYUKI K ...
    1986 Volume 34 Issue 8 Pages 688-704
    Published: August 25, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    Thirty-three cases (Group A: Acute exacerbation of chronic respiratory tract infection, 13 cases. Group B: Pneumonia, 19 cases. Group C: Other, 1 case) of respiratory tract infections caused by P. aeruginosa were administrated the combination of TOB+CFS+FOM which was in vitro synergistic (FIC index≤0.5) against the fresh isolated P. aeruginosa, and clinical efficacy of this combination was evaluated.
    1) The MICs 80 of TOB, CFS and FOM against 33 freshly isolated P. aeruginosa from the 33 cases were 4μg/ml, 32μg/ml and 128μg/ml, respectively. The ranges of FIC index of addition of FOM to TOB+CFS were 0.12-0.50.
    2) Bacteriologically, 24 and 9 out of 33 cases were eradicated and reduced, respectively. Twentyfour (72.7%) out of 33 cases were eliminated. Clinical efficacies resulted in 14 excellent and 19 good cases. Clinical efficacies of both excellent and good were observed in all 33 cases. Concerning side effects, no severe one was observed.
    3) After intravenous drip infusion of 1.0g or 2.0g CFS, 2.0g FOM for one hour and intramuscular administration of 60mg TOB, the serum concentration of each drug reached peak level at one hour in nine cases. The peak of serum concentration was 77.2±24.3 and 101.0±27.9±g/ml, respectively following 1.0g (3 cases) and 2.0g (6 cases) drip infusion of CFS. The peak of serum concentration was 130. 6± 44. 4μg/ml following 2.0g (9 cases) of FOM and 4.5±2.3μg/ml following 60mg (9 cases) of TOB. In Group A (4 cases) the peak of sputum concentrations of CFS, FOM and TOB were 3.4±2.4μg/ml, 7.3±4.0μg/ml and 0.9±0.2μg/ml, respectively, in Group B (3 cases) 3.8±3.5μg/ml, 10.6±7.3μg/ml and 1.5±0.9μg/ml, respectively.
    4) In vitro time-kill studies, antibiotic combination showed stronger bactericidal effects against the isolated strains of P. aeruginosa than single drug.
    We propose that measurements of MIC and FIC index may be a useful guide for treatment of respiratory tract infection caused by P. aeruginosa.
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  • KIKUO ONUMA, KOTARO OIZUMI, KIYOSHI KONNO
    1986 Volume 34 Issue 8 Pages 705-712
    Published: August 25, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    In a previous paper, we have reported the clinical features which were characteristic of drug fever induced by parenteral administration of β-lactam antibiotics and have pointed out that the drug fever was frequently associated with a transient elevation of the serum level of lactate dehydrogenase (LDH), In the present study, the sources from which the increased serum LDH was derived and the significance of LDH for the diagnosis of drug fever were investigated. In addition, the diagnostic value of immunological tests was estimated.
    It was found that, between drug fever episodes with elevated LDH level and those without it, there was no significant difference in the ratio of episodes with a transient elevation of the serum level of glutamic pyruvic transaminase (GPT) which is derived almost exclusively from liver cells.
    The drug fever episodes in the present study were classified into the following three groups, namely, episodes with both a transient and slight decrease of neutrophils and that of platelets (Group I), those with either of them (Group II) and those with neither of them (Group III). Of a total of 20 episodes of drug fever with elevated LDH level, 12 belonged to group I, four to group II and four to group III, respectively. Of a total of 21 episodes of drug fever without elevated LDH level, six belonged to group I, five to group II and ten to group III. Thus it was known that neutrophils and platelets decreased more frequently in drug fever episodes with elevated LDH level than in those without it (P<0.05).
    In ten episodes of drug fever with elevated LDH level, individual activities of five isozymes of LDH were determined twice, namely, when the clinical symptoms were manifest and LDH level was elevated and when patients were recovering from the episodes. Then the differences in the activities between the above two periods were calculated. As the result, a significant change in activity of LDH-3 was demonstrated in six patients and that of LDH-2 in three other patients, respectively.
    These data suggested that the elevated LDH level was caused by a release of LDH mainly from blood cells. Serum LDH level might be a comparatively sensitive indicator of the destruction of neutrophils and platelets, which was possibly caused by the same immune mechanism as that which was responsible for drug fever.
    When hypersensitivity to antibiotics was skin-tested in 15 patients with drug fever immediately before and one week after treatment, only one of them showed a weakly positive Arthus reaction after treatment. A circulating antibody which was specific to the administered β-lactam antibiotic was found, as shown by passive hemagglutination test, in only 5 of 15 patients with drug fever.
    In contrast, migration of leukocytes was inhibited by an antibiotic which was related to drug fever in 9 of 11 patients examined (82%). The mean degree of migration inhibition was higher in patients with drug fever than in those who had received β-lactam antibiotics for more than two weeks without adverse reactions (P<0.05).
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  • JIRO YURA
    1986 Volume 34 Issue 8 Pages 713-738
    Published: August 25, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    A comparative study was performed by a well-controlled method to objectively evaluate: the efficacy safety and utility of imipenem/cilastatin sodium (IPM/CS) compared with ceftizoxime (CZX) in the treatment of purulent peritonitis. IPM/CS and CZX were administered by an intravenousidrip infusion in a daily dose of 1g/1g and 2g, respectively. The following results were obtained.
    1. Clinical efficacy rate was 77.8%(49/63) in IPM/CS group and 77.8%(49/63) in CZX group.
    2. Final overall clinical improvement rate was 93.7%(59/63) in IPM/CS group and 87.5%(56/64) in CZX group, with no statistically significant difference between the two groups.
    3. As for bacteriological effect, the eradication rate in evaluable patients was 87.5%(42/48) in IPM/CS group and 77.3%(34/44) in CZX group, with no statistically significant difference between the two groups. In bacteriological response, the eradication rate was 96.5%(109/113) in IPM/CS group and 95.4%(103/108) in CZX group, with also no statistically significant difference between the two groups.
    4. Side effects were observed in 1 of 72 patients (1.4%) in IPM/CS group and 2 of 71 patients (2.8%) in CZX group, whereas abnormal laboratory findings were observed in 12 of 70 patients (17.1%) in IPM/CS group and 10 of 71 patients (14.1%) in CZX group, respectively. In the incidences of adverse effects and abnormal laboratory findings, there was no statistically significant difference between the two groups.
    5. Overall clinical utility rate was 79.4%(50/63) in IPM/CS group and 76. 6%(49/64) in CZX group, with no statistically significant difference between the two groups.
    It will be considered that these results suggests IPM/CS is a useful drug in the treatment of purulent peritonitis as well as CZX.
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  • JIRO YURA
    1986 Volume 34 Issue 8 Pages 739-772
    Published: August 25, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
    To objectively evaluate the efficacy safety, and utility of L-105 for postoperative infections including postoperative wound infection, a well-controlled clinical study was conducted in comparison with cefotiam (CTM). Each drug was administered 2g daily by intravenous drip infusion. The results were as follows:
    1. Clinical efficacy rates were 81.3%(91/112) for L-105 group and 75.2%(82/109) for CTM group. When the groups were subdivided into wound infection and other infections, the efficacy rates were: in wound infection, 89.6%(60/67) for L-105 group and 89. 4%(59/66) for CTM group, while in other infections group the rates were 68.9%(31/45) for L-105 group and 53.5%(23/43) for CTM group. There were no statistically significant differences between the two groups.
    2. As antibacterial activity the bacterial eradications were examined and the rates were 63.2%(48/76) for L-105 group and 53. 4%(39/73) for CTM group. In wound infection, the rate for L-105 group was 67.3%(33/49) and for CTM group 61.7%(29/47), whereas in other infections, L-105 group showed 55.6%(15/27) and CTM group 38. 5%(10/26). No statistically significant differences were rioted between the two drug groups.
    3. In final overall improvement evaluation, the rate of moderate improvement and above grade was 80.4%(90/112) for L-105 group and 73. 4%(80/109) for CTM group. In wound infection, the rates were 89.6%(60/67) for L-105 group and 87.9%(58/66) for CTM group. In other infections, L-105 group showed 66. 7%(30/45) and CTM group 51. 2%(22/43). No significant defferences were ibserved in any comparison.
    4. Incidence rates of side effects and abnormal laboratory test values were 1.5%(2/130) and 12.3% 14/144), respectively in L-105 group, whereas in CTM group they were 2.3%(3/129) and 12.7% 15/118), respectively, showing no significant difference between the two groups. No serious side ffects or serious abnormal values were reported in either group.
    5. As for the clinical utility of drug evaluated by attending surgeon to his patient the useful rates rere 52.3%(58/113) for L-105 group and 45.5%(50/110) for CTM group. In wound infection, L-105 roup showed 56.1%(37/68), and CTM group 547%(36/67). In other infections, the rates were 6.7%(21/45) for L-105 and 32.6%(14/43) for CTM group. In any comparison no significant difference were shown between the two drug groups.
    From these results, L-105 was considered to be as useful a drug as CTM in the treatment of postoperative infections including postoperative wound infection.
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  • 1986 Volume 34 Issue 8 Pages 773-800
    Published: August 25, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
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  • 1986 Volume 34 Issue 8 Pages 801-817
    Published: August 25, 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
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  • 1986 Volume 34 Issue 8 Pages 822
    Published: 1986
    Released on J-STAGE: August 04, 2011
    JOURNAL FREE ACCESS
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