Cytological effects of 5-Fluorouracil and Mitomycin C on EHRLICH ascites tumor were observed to discuss the method of employment of the drugs. The frequency, of cell divisions and chromosome aberrations were calculated to quantitatively determine the degree of growth inhibition of tumor cells. Cytological characteristics of untreated tumor cells were as follows;
In the peritoneal cavity of each mouse, 7×10⁶tumor cells were inoculated. The body weight increased by days and it was 1.35 g on average on the 4 th day. Mitosis rate was 6. 65% at the top frequency and the mitotic phases were frequent in prophase, telophase, metaphase and anaphase in order from high to low. Average life time of untreated mice bearing tumors was 17. 8 days. The distribution of the chromosome number of the tumors was varied in the range from 42 to 153, and characterized by hypertriploidy 66, 69 and 71 in each sampling, which were stem cell lines. The idiogram analysis indicated that the stem cell contained 1 marker chromosome with secondary constriction and that the remaining chromosomes were acrocentric in shape. Chromosome aberrations such as chromatid gap and breaks were counted about 10% on the 11 th and 23 rd day after inoculation.
On the 4th day after inoculation of the tumor cells 5FU or MMC was injected intraperitoneally at a dose of 25mg/kg or 2mg/kg. In the same way cytological changes were investigated at the time from 30 minutes to 8 days after injection. The experiments were divided into following 4 groups :
5FU-MMC; 2mg/kg of MMC were added 48 hours after injection of 25mg/kg 5FU.
MMC-5 FU; 25mg/kg of 5 FU were added 48 hours after injection of 2mg/kg MMC.
MMC-MMC; 2mg/kg of MMC were added 48 hours after injection of 2mg/kg MMC.
5FU-5 FU; 25mg/kg of 5 FU were added 48 hours after injection of 25mg/kg 5FU.
The cytological effects and prolongations of tne life time were particularly evident in the groups MMC-5FU and 5FU-MMC, excepting in a mouse of MMC-MMC group. However, some of the tumor cells remained unaffected. Almost of these resistant cells were cells of stem cell lines.
The results might indicate that successive combination chemotherapy, in which for instance a large dose of MMC was used intermittently and a continuous small dose of 5 FU followed it, was the most effective application.

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The metabolism of clindamycin, a new lincomycin derivative, was investigated and the following results were obtained.
1) A part of clindamycin is changed into N-demethyl-clindamycin in rats and dogs.
2) One hour blood level of rats with 80 mg/kg phenobarbital pretreatment is higher than those without treatment, andin vitroinactivation study showed the activity in the liver of rat treated as above is less decreased than those non-treated. These studies seem to indicate that a part of clindamycin is metabolized rapidly to the more active N-demethyl-clindamycin in rats pretreated with phenobarbital.
3) N-Demethyl-clindamycin was not found in dog plasma at five hours after 100 mg/kg intravenous administration. Biliary and urinary excretion studies showed as follows : biliary excretion, 1.4-4.4 mcg/ml. urinary recovery, O. 035% of administrated clindamycin.
4) The antibacterial activity of N-demethyl-clindamycin is about two times active than that of clindamycinin vitro. In comparison with clindamycin there is no difference in antibacterial spectrum.
5) It seems that N-demethyl-clindamycin is not directly responsible for the slight histological degeneration, which was found in rat liver after large dose clindamycin administration.

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Thiamphenicol was given orally in a dose of 1.5g daily for 7-14days to 16 patients of chronic obstructive pulmonary diseases aggravated by infection. These patients were subjected to the tests. for pulmonary function, erythrosedimentation rate, expectoration etc. before and after the treatment with thiamphenicol.
Either increase of 30% or more in the spirogram per sencond or normalization in the erythrosedimentation rate were regarded as an improvement of diseases. Seven cases out of them were im proved in both finding, 3 cases were improved in either of the findings.
The results of the sensitivity test of the pathogenic bacteria in sputum revealed that 4 cases were very sensitive (+++), 4 case sensitive (++), 4 case slightly sensitive (+) while the rest 6 cases were resistant. The above results did not quite coincide with the clinical results.
There were two cases who developed such side effects as slight gastro-intestinal disturbance, diarrhea and appetite depression but such side effects desappeared after discontinuation of the therapy with thiamphenicol.
Thiamphenicol was founded to be effective for the treatment of infectious obstructive pulmonary diseases with slight side effects.

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1) The drug sensitivity test for the isolated strains from the samples of the patients was conducted by the disk diffusion method, using 3 kinds of concentration in each disk. As the result of the test, CEX was superior to CER, CET and AB-PC as far as gram negative bacilli are concerned.
2) The concentration of CEX in the organs of rats after the administration was high in the kidney and the liver, moderate in the blood, and low in the lungs.
3) In human beings, the maximum concentration in the blood was 20 mcg/ml in 1 hour after 500 mg of CEX administration, the effective concentration in the blood may be retained for 4 hours. This concentration was 5 times higher than that of AB-PC. The recovery rate of CEX in the urine was 88% within 4 hours after administration. It can be said that the absorption and excretion of CEX are smooth.
4) The application of CEX to the infectious disease of the respiratory organs is considered to be effective as long as the pathogess are gram positive cocci (Pneumococcus, Staphylococcus aureus, etc.). However, it is not so effective for chronic bronchitis, bronchopneumonia, bronchiectasis of which “Hemophilus infiuenzae” takes a part.
5) Any ill effects such as rash, allergic reaction, damage to the liver or the kidney, gastrointestinal distress could not be observed at all.

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It was found that erythromycin is an active inducer for macrolide (Mac) resistance in inducibleresistant strains of S. aureus, but not spiramycin (SP). In this respect, SP is found to be useful in chemotherapy for Mac inducible-resistant strains.
The synergistic action of SP and CP (chloramphenicol) was demonstrated in vitro test for Staphylococcal strains.
Induction for Mac resistance did not take place when CP was added to the induction mixture. Addition of CP also lowered the mutation rate to Mac high resistance in Mac inducible-resistant strains.

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Eighty-six cases of urological infection were treated with rifampicin, including 9 cases of urogenital tuberculosis and satisfactory results were obtained. In 77 common infections 61 were effective (79.4%).
Occasionally there was only a temporary effect. In one case ofStaphylococcus epidermidis-infection and in four cases ofE. coli-infection, rapid appearance of highly resistant strains was observed.
In gonococcal infection daily single oral intake of 900mg of rifampicin was found to be more effective than 600-1, 200mg of rifampicin in four divided doses daily.
In cases of urogenital tuberculosis the results were excellent in three, good in one, somewhat beneficial in one, temporally effective in one, poor in two cases. In one case the result was obscure.
Side effects were rarely encountered. In three cases the drug was not tolerated because of severe nausea and vomiting. Further cases of heavy sensation in the breast, fullness of the stomach and urticaria all over the body were observed.

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