6-mercaptopurine and thioinosine were compared in the metabolism in L 1210 cells in order to investigate whether purine nucleoside was directly phosphorylated to purine nucleoside monophosphate. When homogenates from L 1210 cells were in cubated with [8-¹⁴C] inosine, the major radioactive product from inosine was hypoxanthine. Inhibition of. inosine phosphorylase of homogenates from L 1210 cells by 6-mercaptopurine and thioinosine was observed. When a cell-free extract of L 1210 cells was incubated with 18-¹⁴C inosine or [³H] thioinosine in an ATP regenerating system, the formation of inosinic acid or thioinosinic acid was observed. The reaction showed dependence upon an ATP regenerating system. The experiment in which [8-¹⁴C] 6-mercaptopurine and ribose-5-phosphate were added to the reaction mixture and no thioinosinic acid was found ruled out the conversion of thioinosine to thioinosinic acid via 6-mercaptopurine.
These results indicate that inosine kinase might exist in L 1210 cells, but on a level too low to be detected in the presence of ATP regenerating system. Purine nucleoside might be directly phosphorylated to its nucleoside monophoshpate in L 1210 cells.

View full abstract

Bacteriological and clinical studies of cefmetazole in the field of ophthalmology were performed and the results obtained were as follows.
1. Minimum growth inhibitory concentration of cefmetazole was 12.5μg/ml for KOCH-WEEKS bacillus, 0.39λg/ml for MORAX-AXENFELD diplobacillus, 0.78-1. 58μg/ml for Strept. pneumoniae, 1. 561, 41 ml for Cory. diphtheriae, 0.39μg/ml for N. gonorrhoeae, 0.39-0. 78λg/ml for Strept. hemolyticus, 50-100μg/ml for Strept. viridans, 0.78-1. 56μg/ml for Staph. aureus and>100μ;g/mi for Ps. aeruginosa.
2. The distribution of the sensitivity for 20 strains of Staph. aureus isolated from ocular infections was in the range of 0.78-3.13μg/ml and the peak of them was seen at 1. 56λg/ml in 10 strains (50%).
3. Ocular penetration was examined in the rabbit eye.
1) Intramuscular injection of 50 tng/kg: The aqueous humor level reached the peak value of 2. 6μg/ml after one hour, and the ratio of aqueous level to blood level was 9. 29%, The ocular tissue level at one hour was relatively high in both outer and inner parts of the eye.
2) Intravenous injection of 50 mg/kg: A peak aqueous level of 4.1μg/ml was obtained after 1/2 hour, and the ratio of aqueous level to blood level was 9. 53%. The ocular tissue level was high in both outer and inner parts of the eye.
4. Clinical results: The intramuscular injection of 0.5g once or twice daily, and 1.0g intravenously, 1.0 g or 2.0 g drip infusion once a day were performed.
Excellent or good efficacy was obtained in cases of external hordeolum, lid abscess, corneal ulcer and late infection.
5. Side effects: No allergic reactions were noticed and no abnormal findings in blood, hepatic and renal tests were observed.

View full abstract

Cefoperasone (CPZ) for parenteral use, a new cephalosporin with marked resistance to β-lactamase, was used in 34 patients hospitalized due to infection of abdominal organs: 22 with appendicitis, 6 with cholecystitis and cholangitis and 6 others.
CPZ in a dose of lg was given intravenously during the operation. Tissue specimens of different sites were taken from the removed organs. The materials of purulent ascites, A-bile and B-bile were subsequently taken at intervals. Determination of CPZ concentration was performed according to paper disk bioassay with Micrococcus luteus ATCC 9341 strain.
CPZ concentrations in the A-bile increased quickly soon after injection, and reached high level peak at 30 min to 1 hoyr, then they were very slow decline. CPZ was observed in the B-bile through the gall bladder wall, and reached high level concentration comparative quickly after intravenous injection. CPZ concentration in the gall bladder wall and appendix, was directly proportional to the degree of pathological changes of inflammation.
On the CPZ concentration in patients with peritonitis and cholecystitis, the concentration in purulent ascites or A-bile and B-bile or appendix and gall bladder wall were observed higher than the MIC of CPZ for Escherichia coli and Klebsiella pneumoniae bacilli.
CPZ therefore will be a useful drug when used for chemotherapy of abdominal infected diseases.

View full abstract

Susceptibilities to pipemidic acid of 229 strains of 24 bacterial species were determined by the 2-fold agar dilution method in parallel with the diameter of inhibition zones by the single-disc method.
The experiments demonstrated significant correlation between MIC by the dilution method and diameter of inhibition zone in each of conventional assay of the over-night (about 16 hours) incubation, delayed assay (about 24 hours incubation), and rapid assay (after 3-4 or 5-6 hours incubation), thus confirming applicability of the single-disc assay for pipemidic acid.
Analysis of the data obtained by using pipemidic acid disc containing 50 μg revealed the primary regression equation to be: D (diameter mm)=30.23-10.72log MIC (μg/ml) in conventional assay, p=38. 27-14. 73 log MIC (μg/ml) in delayed assay, D=17.04-4. 34 log MIC (μg/ml) in 3-4 hours rapid assay, and D=23.0-7. 28 log MIC (μg/ml) in 5-6 hours rapid assay, respectively.
The range of variations in MICs estimated from the diameter of inhibition zone by the disc test was then calculated in comparison with that in MIC determined by the two-fold agar dilution assays, as reference for the experimental errors which may be involved in the estimation of MIC of pipemidic acid by the single-disc assay.

View full abstract

A comparative clinical study of cefaclor with cephalexin was carried out by randomized double blind techniques in order to compare the clinical efficacy, side effects and usefulness in treatment of 239patients with acute and chronic bronchitis.
In the cephalexin group, cephalexin was orally administered four times a day at a daily dosage of 1, 000mg for 3 to 10 days. In the cefaclor group, cefaclor was orally administered three times a day at a daily dosage of 750mg for 3 to 10 days and one capsule of placebo was also given every evening in order to keep the blindness of the administration.
Statistical comparisons between the two drugs were made in 159 patients with acute bronchitis and 78 patients with chronic bronchitis. Two patients were excluded from the statistical evaluation due to deviations from the protocol.
In the case of acute bronchitis, characteristics of the population, sex and age, severity of infection and causative organisms before treatment were similar in each treatment group and no significantdifference could be found between the two groups, except for a higher tendency of complications with pulmonary tuberculosis and higher positive CRP in the cefaclor group.
No significant difference was seen in the clinical effectiveness obtained in acute bronchitis between the two drugs. Excellent and good clinical responses were obtained in 57 (74%) of 77 patients of the cefaclor group and in 64 (78%) of 82 patients of the cephalexin group. Regarding the degree of improvement of cough on the 7th day, the cephalexin group showed a superior tendency (p<0.10) to the cefaclor group. On the other hand, the cefaclor group showed a superior tendency (p<0.10) to the cephalexin group in degrees of improvement of rales on the 5th day and final day of administration.
In contrast, backgrounds of the population of chronic bronchitis were quite similar in each group and all items compared showed no significant difference between the two groups.
The clinical effectiveness in chronic bronchitis obtained with cefaclor showed superior tendency (p<0.10) to that with cephalexin. Excellent and good clinical responses were obtained in 28 (67%) of 42 patients of the cefaclor group and in 17 (47%) of 36 patients of the cephalexin group. Regarding the degree of improvement of sputum, treatment with cefaclor showed a superior tendency (p<0.10) to that with cephalexin on the 7th day. At the same time, the degrees of improvement of CRP and ESR treated with cefaclor were significantly superior (p<0.05) to those with cephalexin. In addition, on the final day of treatment, the degree of improvement of cough in the cefaclor group showed a superior tendency (p<0.10) to that in the cephalexin group.
No statistically significant difference could be found in the occurrence of side effects or abnormal clinical laboratory findings between the two groups.
According to the judgement by investigators in charge, no significant difference was seen in clinical usefulness in acute bronchitis between the two drugs.
In the patients with chronic bronchitis, the judgements of clinical usefulness in the cefaclor group was significantly superior (p<0.05) to that in the cephalexin group

View full abstract

In our double-blind study, the clinical utility of ceftizoxime was compared with that of cefazolin in 100 randomly selected patients with acute purulent peritonitis (47 patients in the ceftizoxime groups and 53 in the cefazolin group): 55 patients with perforated appendix, 14 with perforated small or large intestine, 24 with perforated stomach or duodenum, and 7 with other perforated organs. Patients were given by iv drip infusion 1 g of ceftizoxime or 2 g of cefazolin twice a day for 7 days. The results were as follows:
1. There were no significant differences between the two groups in age, sex, body weight, type and severity of diseases, symptoms before treatment and surgical managements.
2. The effectiveness rate evaluated by each surgeon was 80.4% in the ceftizoxime group and 75.5% in the cefazolin group. The effectiveness rate evaluated by the committee was 80. 9% in the ceftizoxime group and 77.4% in the cefazolin group. There was no significant difference between the two groups.
3. Complication of wound infection was observed in 10. 6% of the ceftizoxime group and in 17.0% of the cefazolin group. The usefulness rate was 76. 6% in the ceftizoxime group and 60.4% in the cefazolin group. The usefulness rate was lower than the general effectiveness rate because of the complication of wound infections.
4. The effectiveness rate was 80. 0% in patients with perforated stomach or duodenum of the ceftizoxime group and 64. 3% of the cefazolin group. The marked effectiveness rate in patients with diffuse peritonitis (19.4%) was lower than that in patients with localized peritonitis (35. 5%) of the cefazolin group. However, the marked effectiveness rate in diffuse peritonitis (26.5%) was almost the same as that in localised peritonitis (30. 8%) of the ceftizoxime group.
5. The effectiveness rate in severe cases was 84. 0% in the ceftizoxime group and 63. 3% in the cefazolin group (P<0.1).
6. In the bacteriological effect, gram-positive cocci were eradicated in 89. 5% of the ceftizoxime group and in 92.3% of the cefazolin group. Gram-negative baccilli were eradicated in 92.3% of the ceftizoxime group and in 80.4% of the cefazolin group. There were no statistically significant differences between the two groups. Of the organisms isolated after the treatmet, P. aeruginosa appeared most frequently.
7. Rash was noted in 2 patients of the ceftizoxime group; and phlebalgia in 1 and diarrhea in 1 of the cefazolin group. Eosinophilia, and increased GOT and GPT were observed in each 1 patient of the ceftizoxime group; and increased GPT in 1 and Al-p in 1 of the cefazolin group.

View full abstract

The purpose of this report is to present (1) the sensitivity of minocycline, gentamicin, miloxacin and pipemidic acid to Serratia marcescens isolated from patients with urinary tract infection, and (2) data on 27 patients with serratia urinary tract infection received minocycline.
When inoculum used was 10⁸cfu/ml, peak of minimal inhibitory concentrations (MICs) of minocycline against 26 strains of serratia was 12.5 mcg/ml, gentamicin 6.25-12.5 mcg/ml, miloxacin and pipemidic acid above 100 mcg/ml.
While inoculm used was 10⁶cfu/ml, that of minocycline was 12. 5 mcg/ml, gentamicin 3.13 mcg/ml, miloxacin 25 mcg/ml and pipemidic acid above 100 mcg/ml.
27 patients with Serratia urinary tract infection were given minocycline orally or intravenous drip infusion for 5-14 days, at a daily dose of from 60 mg to 200 mg. In 16 of 27 patients Serratia were eradicated.
Disappearance rate of Serratia in the case with MICs below 6.25 mcg/ml was 84%, and that in the case with MICs 12.5 mcg/ml was 66%. While, it was 0% in the case with MICs above 25 mcg/ml.
In the case with MICs below 12.5 mcg/ml, disappearance rate was 85% when with catheter in the urinary tract, while, it was 40% when without catheter. In the case with MICs above 25 mcg/ml, disappearance rate was 0% regardless of catheter in the urinary tract.
In the case with MICs below 12, 5 mcg/ml, disappearance rate was 36% when received monocycline for 5-9 days, while it was 90% when received minocycline for 10-14 days. But, in the case with MICs above 25 mcg/ml, disappearance rate was 0% regardless of duration of chemotherapy.
4 patients with Serratia urinary tract infection, in those gentamicin was not effective, were given minocycline, and outcome was good in all of them.

View full abstract