The antimetastatic cffccts of organic silicone compounds have been examined in mice bearing Lewis lung carcinoma (3 LL). Of the evaluated derivatives, SDK 110 (2-Trimethylsilylpropylthiopropylamine) administered orally on days 1 to l0, extremely and significantly inhibited lymphatic and pulmonary spontaneous metastases in mice hearing 3 LL. At low doses that do not influence the growth of the primary tumor implant, SIK 110 inhibited spontaneous lymph node and lung metastases. The treatment was most effective when SDK 110 was administered orally consecutively on days 1 to 7 and day 10, or once on day 0 after tumor implantation. Also, SDK 110 markedly inhibited artificial lung metastases in mice by i. v. inoculation of tumor cells. Even when SDK 110 was administered prior to tumor inoculation, a considerable decrease in the number of lung metastatic foci was recognized. These observations are compatible with the hypothesis that the antimetastatic effect of SDK-110 is due to its influence on an important factor of the tumor cells or the host in a metatastatic cascade preventing the release of 3 LL cells from the primary tumor into the circulation, and hence their arrest and extravasation into secondary sites.

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We investigated in vitro and in vivo synergistic effects of ceftizoxime and gentamicin on their bactericidal activity and postantibiotic effect (PAE) against Serratia marcescen, and obtained the following results:
1 The in vitro postantibiotic effect of ceftizoxime was more prolonged when given in combination with gentamicin than when given alone.
2. The in vivo postantibiotic effect of ceftizoxime was more prolonged in a systemic and a calf infection when the drug was given in combination with gentamicin than when given alone.
3. The bactericidal activity of ceftizoxime was more marked and the postantibiotic effect was more prolonged in an in vitro kinetic model simulating human plasma levels when given in combination with gentamicin than when given alone.

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In an attempt to develop a transdermal therapeutic system for Zidovudine, percutaneous absorption of the drug was examined in rats and human skin.
The ability of several penetration enhancers to increase transdermal delivery of Zidovudine was evaluated in excised rat skin. Azone (1-dodecylazacycloheptan-2 one) showed a significant enhancing effect at a concentration of 3% in water. The enhancing effect was increased in the presence of N-methyl-2-pyrrolidone (MP); Zidovudine solution (5mg/ml) containing 3% Azone and 20% MP showed 492-fold enhanced permeation compared to application of Zidovudine alone.
A Zidovudine solution containing Azone (3%) and MP (20%) was applied on rat abdominal skin, and the plasma concentration was measured. Zidovudine was detected in plasma at 4 h after the application, and a constant plasma concentration (2-3 μM) was maintained for 6 h.
The permeation of Zidovudine was also examined in human skin. A gel formulation containing Azone and MP showed a considerable permeation rate of Zidovudine. Our results suggest that transdermal application of Zidovudine can be useful in obtaining an effective plasma concentration (1 μM) and maintaining it for a long time.

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Histopathologically, inflammation of the lungs in 60-week-old mice with respiratory tract infection induced by exposure to Klebsiella pneumoniae by aerosol was more severe than that in 4-week-old mice. We studied the therapeutic effect of antibiotics in the aged mice with respiratory tract infection. ED₅₀ values of ceftizoxime and cefoperazone were 0.32 and 1.41mg/kg in 4-week-old mice with K. pneumoniae infection. In 60-week-old mice, ED₅₀ values were 8.98 mg/kg for ceftizoxime and 57.5mg/kg for cefoperazone, and the efficacy decreased 27- and 40-fold. The difficulty in treating aged mice suggests that the host defense against respiratory tract infection was degraded by a decline in the function of phagocyte cells and in the concomitant bactericidal activity of antibiotics with the phagocyte cells.
On the other hand, the additive and synergistic effects were obtained by the combination of ceftizoxime with gentamicin and of ceftizoxime with an immunopotentiator, FK 565, and these effects were due to enhancement of the bactericidal activity against K. pneumoniae or restoration of host defense factors.

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We studied the role of immediate and delayed type hypersensitivity (DTH) in beta lactam-induced hypersensitivity by performing a leucocyte migration inhibition test (LMIT), which proves the development of DTH, and by measuring serum antibodies by enzyme linked immunosorbent assay (ELISA).
1. An LMIT was performed in 89 patients with suspected beta lactam antibiotic allergy 50 with drug rash, 29 with drug fever, 24 with hepatopathy, 12 with eosinophilia and 2 with anaphylaxis, some patients having two or more concomitant symptoms). The LMIT was positive at a high rate of 74 %(66 cases).
2. In contrast, ELISA was positive in only 8%(7 cases), with IgG in 2 and IgM in 5 cases.
3. The LMIT results showed high correlation for the 35 drugs tested, except for latamoxef, which was positive in only one of four cases. In contrast, the ELISA was positive at a high rate for ceftizoxime (3/5 cases) and cephalexin (2/4 cases).
4. The LMIT was positive in 56-100 % in patients with symptoms other than urticaria, while ELISA was positive in only 0-20 % of the symptoms.
5. The seven patients who showed a positive response in the ELISA were also positive in the LMIT, suggesting that cellular and humoral immunity play a role in some patients with beta-lactam antibiotic allergy.

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Thirty patients undergoing transurethral prostatectomy administered 400 mg of cefixime on the morning of surgery and 200 mg twice a day from the next morning. Twenty-five patients without pre-operative UTI developed neither fever nor UTI postoperatively. Four of the five patients with pre-operative UTI became sterile and none needed additional intravenous antibiotics.

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We studied 5 clinical cases, incluiding 3 infants with sepsis duc to mycetes with respect to antibiotics used prior to the onset of the disease, background factors and clinical course We also discuss the early diagnosis, treatment and prevention of mycosis. Two of three infants were minimal premature infants weighing 1, 500g or less at birth, and all three cases had received intratracheal intubation. Some broad spectrum antibiotics had been administered in all the cases and an indwelling catheter (e. g. umbilical or intravenous) was used in 4 of the 5 cases. Our results agreed with previous reports on the background factors of this disease. As to the pathogenic mechanism of mycosis, it is thought that, due to the changes in bacterial flora during administration of antibiotics, mycetes proliferate in the intestinal canal, eventually leading to the development of mycosis. Consequently, mycetes tend to be found earlier in fecal than in urine and blood cultures. Hence the fecal culture is useful in the early diagnosis of mycosis. Furthermore, as a method of preventing mycosis due to a change in intestinal flora, it is neccesary to select antibiotics with the least influence on this flora.
Miconazole (MCZ), a new anti-mycotic agent which is an imidazole derivative, was used in 4 of 5 cases, all of which responded well whithout adverse reactions. Especially the fact that MCZ was effective in premature infants suffering from side effects due to combination therapy with amphotericin B and 5-fluorocytosine suggests that MCZ is a safe and useful drug in pediatrics.

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Epidemiological studies have revealed that the isolation frequency of methicillin-resistant Staphylococcus aureus (MRSA) strains has increased from year to year and is much higher in in-patients than in out-patients. Drug resistance in recent isolates of MRSA strains has increased toward various drugs, i.e., cephems, penams, aminoglycosides, new quinolones, etc. Similarly, the levels of resistance in recent MRSA isolates are increasing from year to year. It was found that glycopeptide (vancomycin and teicoplanin) and rifampicin are still effective against MRSA.
The posibility of nosocomial infection with MRSA, isolation of MRSA from patients, treatment of MRSA patients and prevention of the spread of MRSA strains in hospital are described.

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