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Three contact allergens; dinitrochlorobenzene (DNCB), nickel and formalin, were determined allergenicities. Contact allergies were induced in 24 dogs and 15 guinea pigs (used as a comparative animal species) by means of Draize test, Maximization test, Open Epicutaneous test and Buehler test, and evaluated by means of closed patch testing. Results showed that, in dogs, nickel produced allergic responses of the skin in the Open Epicutaneous test, but formalin did not produced it. In the Maximization test, however, both nickel and formalin failed to induce a contact allergy, although DNCB showed a high allergenicity. The appropriate concentration of test solutions for the closed patch test in dogs were 1.0% for DNCB, 0.1% for nickel and 1:10 dilution for formalin, respectively.

An anomalous negative temperature dependence of electrical resistivity has been observed in $({\mathrm{Fe}}_{1\ensuremath{-}x}{\mathrm{V}}_{x}{)}_{3}\mathrm{Al}$ alloys with V compositions up to $x\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}0.35$. In particular, the Heusler-type ${\mathrm{Fe}}_{2}\mathrm{VAl}$ compound is found to be on the verge of magnetic ordering and to exhibit a semiconductorlike behavior with the resistivity reaching $3000\ensuremath{\mu}\ensuremath{\Omega}\mathrm{cm}$ at 2 K, in spite of the possession of a clear Fermi cutoff as revealed in photoemission valence-band spectra. A substantial mass enhancement deduced from specific heat measurements suggests that ${\mathrm{Fe}}_{2}\mathrm{VAl}$ is a possible candidate for a $3d$ heavy-fermion system.

An anomalous negative temperature dependence of electrical resistivity has been observed in (Fe1-xVx)3Al alloys with V compositions up to x = 0.35. In particular, the Heusler-type Fe2VAl compound is found to be on the verge of magnetic ordering and to exhibit a semiconductorlike behavior with the resistivity reaching 3000 μΩ cm at 2 K, in spite of the possession of a clear Fermi cutoff as revealed in photoemission valence-band spectra. A substantial mass enhancement deduced from specific heat measurements suggests that Fe2VAl is a possible candidate for a 3d heavy-fermion system.

We investigated the influence of meteorological variability on the interannual variation of the springtime boundary layer ozone over Japan during 1981–2005 by multiyear simulations with the Models-3 Community Multiscale Air Quality (CMAQ) modeling system and the Regional Emission Inventory in Asia (REAS). CMAQ/REAS generally reproduced the observed interannual variability of springtime ozone over Japan, showing year-to-year variations larger than the annual rate of increase of the long-term trend. We then analyzed the influence of the interannual variation of meteorological fields in simulated results by using the fixed emissions for 2000 and meteorology data for each year. As a reference parameter, we calculated the area-weighted surface pressure anomaly over the Pacific Ocean east of Japan. When the anomaly has a large negative value, polluted air masses from continental Asia tend to be transported directly to Japan by westerly winds. In contrast, when the anomaly has a large positive value, the influences of the outflow from continental Asia tends to be small because the westerly components of wind fields around Japan are comparatively weak. Instead, southerly winds are relatively strong and transport clean air masses from the Pacific Ocean to Japan. Consequently, springtime ozone over Japan is higher (lower) than in ordinary years when the anomaly has a large negative (positive) value. In general, the interannual variation of springtime ozone over Japan is sensitive to the outflow from continental Asia. We also found some correlation between springtime ozone over Japan and the El Niño-Southern Oscillation, indicating that higher and lower springtime ozone over Japan are related to La Niña and El Niño, respectively. Differences in the meridional displacement and diversity of cyclone tracks near Japan between El Niño and La Niña years may be responsible for interannual variations in the springtime boundary layer ozone over Japan.

Pharmacokinetic and clinical studies on flomoxef (FMOX) in the perinatal period were carried out. The results are summarized as follows. 1. The concentration of FMOX in umbilical cord serum was about 10 micrograms/ml in about 30 minutes after 1 g one shot intravenous injection. Amniotic fluid concentration was 7 micrograms/ml in 41 minutes after administration. By 1 hour intravenous drip infusion, FMOX concentration in umbilical cord serum was about 5 micrograms/ml in 2-3 hours after administration. Amniotic fluid concentration of about 20 micrograms/ml was found in 1 case. 2. FMOX 1-2 g x 2-3/day was given by intravenous drip infusion to 7 cases of perinatal infection for 4-26 days. Clinical efficacies were evaluated a good for all cases. Neither side effect nor abnormal laboratory test value was observed. Consequently, FMOX was considered to be highly effective and safe for its clinical use in perinatal period infections.

Filarial glomerulonephritis was studied using Dirofilaria immitis infected dogs. Of 34 infected dogs examined, 15 dogs (44.1%) had histopathological lesions in the kidney. These lesions included an increased number of mesangial cells and increased thickness of the matrix, the infiltration of the small round and plasma cells into the interstitium and thickening of the basement membrane. Deposits of IgG were demonstrated in the infected dogs, whereas C3 deposits were found in all dogs. Combined immunoglobulin and complement deposits were not always found in the dogs with histopathological lesions. The mean concentration (expressed as absorbance) of circulating immune complexes (CIC) was 0.675 +/- 0.517 in infected dogs, and 0.132 +/- 0.092 in uninfected dogs. Although there was significant difference in the level of CIC between infected and uninfected dogs (P less than 0.001), 11 dogs (32.4%) in infected group were negative. Otherwise, the CIC levels were correlated to the adult worm burden (r = 0.848; P less than 0.001) but not to the number of circulating microfilariae (mf) (r = 0.398; P less than 0.05). Transfer of mf to 7 naive dogs was performed to clarify the role of mf in the pathogenesis of filariasis. Antibodies to crude mf antigen became detectable two weeks after the transfer. Neither pathologic findings nor deposits of IgG and C3 in the kidney were found in dogs examined 20 days or 70 days after transfer. There was no evidence that histopathological lesions were induced by live mf, suggesting that adult worm burdens may be more closely related to filarial nephropathy.

Many cephalosporin antibiotics have recently been invented and attempts have been made to use them clinically. The choice of which of these drugs should be used has been difficult in gynecology. The efficacies of these drugs depend on their antibacterial spectra, potencies, and concentrations in tissues. This study was designed to investigate the pharmacokinetics of various cephem antibiotics in the exudate of the retroperitoneal space that is formed after radical hysterectomy and pelvic lymphadenectomy. These cephem antibiotics were cefoxitin, cefotiam, cefotetan, cefpiramide, cefminox, cefotaxime, ceftizoxime, cefoperazone, cefmenoxime, cefbuperazone, ceftazidime, cefpimizole, flomoxef, and cefuzonam. The maximum concentrations after administration of a 1-g dose in the exudate of the pelvic retroperitoneal space were 37.9 micrograms/ml with cefminox, 30.3 micrograms/ml with cefpimizole, 21.6 micrograms/ml with flomoxef, 21.5 micrograms/ml with ceftazidime, and 17.6 micrograms/ml with cefbuperazone, which were relatively high. When selecting antibiotics for prophylactic use against infections in the retroperitoneal space after radical hysterectomy and pelvic lymphadenectomy, on the basis of drug transfer, flomoxef, cefminox, cefbuperazone, ceftazidime, and cefpimizole were considered to be the drugs of first choice at a dose of 1 g.

Over the past 35 yr, diethylcarbamazine (DEC) has been the most widely used agent for the treatment of filarial diseases, particularly in onchocerciasis. The microfilaricidal action of DEC has been recently shown to be mediated by blood platelets with the additional triggering of a filarial excretory Ag (FEA). This FEA could be detected by using mAb in the serum of infected patients. By using one mAb (IA2(23] directed against Onchocerca volvulus and recognizing circulating Ag (Ab1), we purified by affinity chromatography the target molecule of IA2(23) (an O. volvulus glycoprotein recognized by IA2(23) mAb). This compound had a dose-dependent effect on the cytotoxic action of DEC-treated platelets. We subsequently produced an anti-idiotype mAb to Ab1 (Ab2), and considered the possibility of replacing the O. volvulus glycoprotein recognized by IA2(23) mAb by Ab2. Ab2 was selected according to its ability to inhibit the binding of radioiodinated Ab1 to the filarial target Ag. It induced the production of anti-O. volvulus antibodies (Ab3) in rats. At a constant concentration of DEC platelets, the addition of increasing amounts of Ab2 led to a dose-dependent cytotoxic effect against parasite larvae. Experiments performed with Ab2 on detergent solubilized surface proteins of platelets identified four bands of Mr 18, 26, 43.5, and 100 kDa, supporting the idea of the presence of binding sites on the platelets for a FEA required for the microfilaricidal cytotoxicity of DEC-treated platelets.

Pharmacokinetics and clinical studies on the perinatal use of latamoxef (LMOX, Shiomarin), a new parenteral oxacephem antibiotic, were carried out and the results obtained were as follows: After LMOX was intravenously given to mother at a dose of 1 g, the umbilical cord serum concentration of LMOX reached to peak with 18.4 micrograms/ml in 1 hour 20 minutes and its concentration was higher than the maternal serum after 2 hours 25 minutes and decreased gradually (T 1/2 beta = 1.61 hours). The materno-fetal transfer of LMOX was 71.0%. LMOX showed the good transfer as well as other cephalosporins. After LMOX was intravenously administered to mother at a dose of 1 g, LMOX concentration in milk wasn't detectable up to 12 hours. LMOX was intravenously administered to 18 cases with premature rupture of membrane, at a daily dose of 2 g for 3--6 days. The prophylactic effects were observed in all cases, both mother and neonate. No adverse effects were observed in mother except for 1 case with low grade abnormality of S-GPT, transiently. We observed 3 neonates with jaundice (total bilirubin greater than or equal to 17.0 mg/dl) probably not related to LMOX. It is concluded that LMOX is less toxic, safe and clinically useful antibiotic for the treatment of perinatal infections.

Concentrations of ceftazidime ( CAZ ) were examined in the pelvic dead space exudate in 6 patients who received radical hysterectomy due to uterocervical cancer. Data analysis was performed by the simulation curves prepared from pharmacokinetics parameters using the three-compartment model. Following 1-hour intravenous drip infusion of 1 g of CAZ , the mean drug concentration in venous blood was 75.54 micrograms/ml at 1 hour after start of the infusion. The mean CAZ level in the pelvic dead space exudate was as high as 23.87 micrograms/ml at 2.09 hours after start of the infusion, and the AUC was 149.11 micrograms . hr/ml. The above results suggest that CAZ is a useful drug clinically with good penetration into the pelvic dead space.

This paper, is concerned with fundamental and clinical studies of ceftizoxime, a newly developed cephalosporin derivative, in the field of obstetrics and gynecology. 1. Concentrations of ceftizoxime after administration 1 g of ceftizoxime by 1 hour drip infusion were determined in genital organs in 17 patients and the exudate of pelvic dead space in 6 patients. Simulated maximal concentrations with the ratios to the simulated peak serum levels were as follows: 27.9 micrograms/g for fundal myometrium with the ratio of 48%, 36.0 micrograms/g for portio vaginalis with 62%, 17.1 micrograms/g for ovary with 29%, 15.0 micrograms/g for oviduct with 26% and 16.2 micrograms/ml for the exudate of pelvic dead space with 30%. 2. Minimal inhibitory concentrations of ceftizoxime were determined against clinically isolated organisms from female genital infectious diseases. Ceftizoxime was found to have a potent in vitro activity against Gram negative bacilli; for example, 0.1 microgram/mg or low against E. coli and K. pneumoniae. Against P. aeruginosa, P. cepacia and b. fragilis, ceftizoxime had an activity which expected to be effective in the clinical use. 3. We gave ceftizoxime to 6 patients comprising 4 patients with puerperal fever, 1 with septic abortion and 1 with tubo-ovarian abscess in daily doses of 2 to 3 g by b.i.d or t.i.d intravenous drip infusion for 4--12 days. The results of the treatment were 'excellent' in 3 patients, 'good' in 2, and 'unevaluatable' in 1. 4. Adverse reactions occurred in 2 patients who showed eruption during the medication with ceftizoxime. These patients had allergic histories due to penicillin derivatives. From the above results it is concluded that ceftizoxime is a useful drug for infections in obstetrical and gynecological field.

The concentration of cefoxitin (CFX, Merxin) in dead space exudate was studied in 14 patients following total extirpation of diffuse uterine cervical cancer. A two-compartment model was used for the analysis. The results obtained were as follows: Calculated maximum concentrations of CFX in the pelvic dead space exudate were 26.55 micrograms/ml at 2.11 hours, 31.07 micrograms/mg at 2.01 hours and 51.51 micrograms/ml at 2.10 hours after 1 hour intravenous drip infusions of CFX 2, 3 and 4 g, respectively. These concentrations were higher than the MIC80 of 12.5 micrograms/ml against E. coli and B. fragilis and were maintained for a sufficient period of time. Based on the results of this study, CFX is considered to be an important and valuable drug in the field of obstetrics and gynecology.

Following an intravenous injection of ceftazidime (CAZ) 1 g, the ratio of transfer of the drug into a fetus was 59.9%, and umbilical serum concentrations of the drug reached the peak of 18.2 micrograms/ml at 1.5 hours, and were slightly higher than maternal serum concentrations at 2.93 hours and after, with half-life of 1.37 hours, the same as in maternal serum. Following an intravenous injection of CAZ 1 g, concentrations of CAZ in mother's milk at 2 hours after injection were 1.16 micrograms/ml on the 4th day of the treatment of CAZ, and 0.86 micrograms/ml on the 7th day. The CAZ was administered to cases of premature rupture of membrane. The prophylactic efficacy against puerperal infections in mothers was 92%, and that against fetal infections in neonates was 96.7%. The CAZ was also administered after cesarean section, and the prophylactic efficacy against postoperative infections was 93.3%. Neither subjective/objective adverse effects nor abnormal laboratory findings for which CAZ was suspected were observed in any mothers or neonates. From the above results demonstrating satisfactory maternal transfer into fetuses and the high degree of safety in fetuses and neonates, as well as its high antibacterial activity, CAZ is considered to be a useful drug for the treatment of perinatal infections.

T-1982 (cefbuperazone) concentrations in antecubital venous blood and pelvic dead space exudate were examined in 4 patients who had received radical hysterectomy due to uterocervical cancer. Data analysis for the transfer of T-1982 into pelvic dead space exudate was performed with the stimulation curves prepared from pharmacokinetic parameters by the three-compartment model. When T-1982 was given at a dose of 1 g, the peak level in the venous blood was 83.7 micrograms/ml at 1 hour after the start of administration. With regards to T-1982 concentration in pelvic dead space exudate, the peak level of 19.3 micrograms/ml was observed at 2.24 hours after the start of administration and relatively high concentration of about 6.1 micrograms/ml was observed even at 8 hours after the start of administration. From the above results, it is concluded that T-1982 is a useful drug for the treatment of infections in the field of obstetrics and gynecology.

To evaluate the efficacy of imipenem/cilastatin sodium (IPM/CS) in the field of obstetrics and gynecology, fundamental (measurement of IPM/CS concentrations in mothers' milk) and clinical studies were performed. Concentrations of IPM/CS in mothers' milk were measured every 1 hour up to 6 hours after a 30-minute drip infusion of 500 mg/500 mg of IPM/CS. IPM/CS was distributed similarly to other cephalosporins. In the clinical study, a 500 mg/500 mg dose of IPM/CS was administered to 5 patients with puerperal intrauterine infections and to 3 patients with urinary tract infections by a 30-minute drip infusion b.i.d. or t.i.d. Good responses were observed in all 8 patients, though the infections were mild or moderate. From these results, IPM/CS appeared to be a useful drug for the treatment of perinatal infections.

Excretion of ceftriaxone (Ro 13-9904, CTRX) into female genital organs was studied by determining its concentration in the dead space exudate of the patients who received radical hysterectomy due to uterocervical cancer. Data analysis was performed by the three-compartment model. The serum peak level of CTRX in the cubital vein was 177.74 micrograms/ml 1 hour after the initiation of intravenous drip infusion for 1 hour with 1 g. The concentration of CTRX in the exudate of pelvic dead space reached a peak of 62.75 micrograms/ml 4.61 hours after the start of administration and still showed a very high level of 25 micrograms/ml at 24 hours. The AUC of the excretion into the exudate of pelvic dead space was 1,432.43 micrograms X hr/ml. These results indicate that CTRX is a clinically useful drug, being excreted into the exudate of pelvic dead space favorably.

The study group was organized to evaluate the usefulness of cefmenoxime (CMX) injection, a new synthetic cephalosporin, for the treatment of infections in the field of obstetrics and gynecology. Fundamental and clinical studies were made by the society and the following results were obtained. 1. The peak distribution of CMX's MIC for E. coli, Klebsiella sp., Enterobacter sp., Bacteroides sp. and Peptococcus sp. isolated from obstetrical and gynecological infections with relatively high frequencies area 0.1, less than or equal to 0.05, 0.2, 3.13, 1.56 micrograms/ml, respectively, with an inoculation of 10(6) cells/ml. 2. When 1 g of CMX is administered by intravenous drip infusion for 1 hour, the maximum concentrations in various tissues of female genital organs were as follows: 14.2 and 13.2 micrograms/g in ovary and oviduct, respectively, at 1.20 hours after the start of administration, and 16.9 and 26.3 micrograms/g in corpus uteri and cervix uteri, respectively, after 1 hour. As for the transfer to the exudate in the pelvic dead cavity, the peak concentration was 15.6 micrograms/ml after 2.13 hours. 3. In the clinical studies, CMX was given to 258 cases with female genital organ infections and others. As for the clinical effects, with exclusion of 3 cases in which other antibiotics are concomitantly used, responses were excellent in 76 cases, good in 162 cases and poor in 17 cases, among 255 cases in total. The efficacy rate was 93.3%. The efficacy rates by diseases were 97.1% (68/70) for intrauterine infections, 88.8% (79/89) for intrapelvic infections, 98.4% (62/63) for adnexitis, and 100% (23/23) for infections of external genital organs. As for the clinical effects on causative bacteria, the efficacy rates were 100% (19/19) for single infections due to Gram-positive bacteria, 94.8% (55/58) for single infections due to Gram-negative bacteria, and 88.2% (15/17) for single infections due to anaerobic bacteria. And its efficacy rates were 89.6% (69/77) for mixed infection cases. Side effects were observed in 2 cases (0.8%); 1 case with eruption, and 1 case with diarrhea and vomiting. As for abnormal laboratory findings, lower white blood cell count was observed in 2 cases and elevation of the values regarding hepatic functions in 9 cases. All cases were returned to the normal after the completion of the administration. Cefmenoxime showed a satisfactory clinical efficacy and a potent bacteriological effect in treatment of the infections in the field of obstetrics and gynecology, and it has been concluded that cefmenoxime will be useful addition to the antibiotics for the therapy of these infections.

Ten cases of gynecological infection were treated successfully by a new cephalosporin derivative, cefotaxime (HR 756, CTX), which proved excellent in 4 cases and good in 6 cases. No adverse reaction was found to be induced by administration of this drug. Post-administration results were all normal for both renal and hepatic function tests. It is extremely difficult to accurately assess bacteriological efficacy of a drug in treatment of female genital infections. Nevertheless, we determined its MICs for a few number of strains we could isolate from clinical cases. Its MIC against 4 strains of B. fragilis inoculated at 10(8) cells/ml was 25 approximately 50 mcg/ml and was 1.56 approximately 3.13 mcg/ml at 10(6) cells/ml inoculation. Its MIC against 2 strains of Ps. cepacia was 12.5 mcg/ml at 10(8) cells/ml inoculation and 6.25 mcg/ml at 10(6) cells/ml inoculation. These MICs suggest that this drug is a very promising antimicrobial agent for treatment of gynecological infections, as been already indicated by clinical results of this drug.

In order to determine transference of cefminox (CMNX, MT-141) into the female genital organ tissues, the drug concentration in the pelvic dead space exudate was measured in cases undergone radical hysterectomy due to uterocervical cancer. For analysis of data the three-compartment model was used. When CMNX was given at a dose of 1 g as an intravenous drip infusion taking 1 hour, the serum concentration of the cubital vein reached its peak of 89.53 microgram/ml at 1 hour after start of administration. In the pelvic dead space exudate the peak concentration of 39.84 microgram/ml was reached at 2.55 hours after administration and a concentration higher than 7 micrograms/ml was still detected even at 12 hours. The area under the curve (AUC) for CMNX concentration in the pelvic dead space exudate was 295.63 microgram X hr/ml. These results suggest that CMNX achieves high concentration in the pelvic dead space exudate and that it is an antibiotic with clinical utility. CMNX was used in the treatment of 6 cases of obstetrical and gynecological infections. The clinical results were excellent in 1 case, good in 2 cases and poor in 2 cases. In the remaining 1 case the results was unknown.

A new semisynthetic penicillin aspoxicillin (ASPC, TA-058) has been evaluated in regard to distribution into the genital organs and the dead space fluid and also in regard to antibiotic activity against various strains clinically isolated in the field of gynecology. The pharmacokinetic studies were made by using two-compartment model on the data of concentration in ovary, oviduct, endometrium, myometrium, cervix uteri and portio vaginalis of the genital organs and in dead space fluid. The following results were obtained. After one shot intravenous administration of 2.0 g ASPC, no marked difference was observed in concentration pattern between peripheral vein and uterine artery. Half-lives were 1.8 hours and 3.5 hours, respectively. The concentrations in various tissues of genital organs reached to the maximum at 36.2-73.6 micrograms/g during 0.07-0.44 hour with half-life varied from 0.53 to 1.3 hours. Area under the curves (AUC) of various tissues were reached to 30-65% of that uterine artery. After 2.0 g administration of ASPC drip intravenously (d.i.v.; for 30 or 60 minutes), there are no remarkable difference on simulation curve of concentration between peripheral vein and uterine artery. The peak level of various tissues attained to 22.5-40.3 micrograms/g during 0.53-0.56 hours and AUC of their concentration achieved about 20-40% of that of uterine artery after intravenous drip infusion for 30 minutes. After intravenous drip infusion for 60 minutes, tissue level reached to the maximum during 1.01-1.82 hours with half-life of 0.65-1.4 hours and AUC of tissue concentration achieved about 20-57% of that of uterine artery. The concentration of the drug in dead space fluid was reached to the maximum at 3.1 hours after the administration and its half-life was 5.3 hours. The in vitro activities of ASPC against clinical isolates were examined. The values of MIC70 and MIC80 were ranged 0.35-5.1 micrograms/ml against S. aureus, S. epidermidis, E. faecalis and P. mirabilis, respectively. Against E. coli, the value of MIC70 was attained 2.9 micrograms/ml, however, the value of MIC80 was more than 100 micrograms/ml due to the two-peaked activity of this drug against the bacteria. AUC and duration time of various tissue concentration were scrutinized regarding to the value of MIC80 of ASPC against S. aureus, S. epidermidis, E. faecalis and P. mirabilis.(ABSTRACT TRUNCATED AT 400 WORDS)

Patients, who had undergone cesarean sections, and those who had experienced premature rupture of membranes, received cefotiam (CTM) and the clinical efficacy and the safety for mothers and fetuses were investigated. At the same time, pharmacokinetic analysis was done to study the maternal fetal transfer. Following results were observed. In cases of premature rupture of membranes, the maternal-fetal transfer ratio after intravenous administrations of CTM was 50.3% at a dosage of 1 g. Maternal and fetal serum concentrations of CTM were maintained higher levels than the MIC80 (0.78 micrograms/ml) against major pathogens excluding anaerobic of gynecologic-obstetric infections and were maintained up to 5.87 hours and 6.15 hours in mothers and fetuses, respectively. The CTM was administered once every 12 hours at a dosage of 1 g to 38 cases up to the 3rd or 4th day of puerperium after the rupture of membranes. Also, the CTM was administered up to times of delivery to another 20 cases, in one of which the fetus developed pneumonia. The maternal-fetal prophylactic effect was recognized in 98.3% (57/58) of cases. Forty-three cesarean section cases received CTM at a dosage level of 1 g by one-hour intravenous drip infusion in the following manner: after surgery to the 4th day, twice a day; from the 5th to the 7th day, once a day. Postoperative prophylactic effect against infection was achieved in all the cases. In 1 case, a slight transient elevation in the maternal GOT was observed. Neonatal jaundice with total bilirubin levels higher than 15.0 mg/dl was observed in 19 neonates (32.8%) in the group in which premature rupture of the membranes had occurred. However, the cause/effect relationship between CTM and the total bilirubin levels is unclear. The maternal-fetal transition of CTM was excellent, and the safety toward the fetus and neonate was high. When an antimicrobial activity and pharmacokinetics are considered, CTM will be a useful drug in the treatment of perinatal infections.

In patients undergoing radical hysterectomy for cervical cancer, suprapubic bladder drainage by INGRAM's trocar catheter, which was removed when the postvoiding residual urine was under 30 ml, was attempted to reduce urinary tract infection. The incidence of urinary tract infection was 63.6% during 4 weeks after radical hysterectomy. Most appeared on the 7-14 th postoperative days. In the 6 months after radical hysterectomy, the incidence of significant bacteriuria in the suprapubic group was 9.4% compared to 21.1% in the urethral catheterized group. The difference between the two groups is significant. In view of these results the following is suggested: 1) The antibacterial mechanisms of both the urethra and urinary bladder are greatly weakened immediately following radical surgery for cervical cancer due to organic changes occurring as a result of the surgery. Urethrovesical reflux can regurgitate bacteria from the urethra into the bladder and cause infection despite the absence of urethral catheterization. 2) Indwelling and frequent urethral catheterization for residual urine may cause a chronic urethritis which may prove to be the greatest factor predisposing to urinary tract infection following radical surgery for cervical cancer.

To study the transfer of cefuzonam (CZON, L-105) into female genital organs, concentrations of the compound in pelvic dead space exudate were measured in cases of radical hysterectomy due to cervical cancer and analyzed by the two-compartment model. When CZON 1 g was drip-infused intravenously, the concentration in the cubital vein blood was 46.95 micrograms/ml at 1 hour after the start of infusion. Concentrations in the pelvic dead space exudate reached the peak of 11.29 micrograms/ml at 2.44 hours after the start, were higher than 4 micrograms/ml after 8 hours and were higher than 1.7 micrograms/ml after 12 hours. The area under the concentration-time curve in the pelvic dead space exudate was 77.85 micrograms X hr/ml. From these results CZON was considered to be effective when administered at 1 g against infections of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, and haemophilus influenzae, but increased dose levels seemed necessary against infections of Staphylococcus epidermidis and Bacteroides fragilis. In 3 cases of obstetric and gynecological infections the efficacy of CZON was good in 2 cases and unknown in the other case.

Concentrations of sulbactam/cefoperazone (SBT/CPZ) in the pelvic dead space exudate were examined in 5 patients who received radical hysterectomy due to uterocervical cancer. Data analysis was performed by the simulation curves prepared from pharmacokinetics parameters using a three-compartment model. Following 1 hour intravenous drip infusion of 2 g of SBT/CPZ, the mean drug concentration in venous blood was 50.62 micrograms/ml for SBT and 120.16 micrograms/ml for CPZ at 1 hour after start of the infusion. The peak SBT level in the pelvic dead space exudate was 21.24 micrograms/ml at 1.58 hours after start of the infusion. The peak CPZ level was 19.13 micrograms/ml at 3.46 hours after start of the infusion. In the treatment of 4 cases with gynecological infections, the clinical efficacy of SBT/CPZ was assessed as effective in 3 cases and poor in 1 case.

Aztreonam (AZT) was studied for the transfer into the pelvic dead space exudate in 5 patients who received radical hysterectomy due to uterocervical cancer, and for the clinical efficacy in the treatment of 5 cases of obstetrical and gynecological infections. Transfer into the pelvic dead space exudate Data analysis was performed by the simulation curves prepared from pharmacokinetic parameters using the two-compartment model. On examination, the serum concentration of cubital venous serum was found to be 53.20 micrograms/ml at 1 hour after the start of 1-hour intravenous drip infusion of 1 g of AZT. Also, the shifting concentration of the pelvic dead space exudate was found to have reached its peak value of 12.79 micrograms/ml at 3.22 hours after the start of the infusion, and still showed the value of more than 7 micrograms/ml even at 8 hours after the start of the infusion. The AUC was 112.81 micrograms X hr/ml. Clinical evaluation AZT was administered at a daily dose of 2-4 g in 2 divided doses by intravenous injection and intravenous drip infusion for 60 minutes. Clinical efficacy of the 5 patients with acute and moderate degree obstetrical and gynecological infections was; excellent in 1 case, good in 3 cases and poor in 1 case, with the overall efficacy rate of 80.0%.

A clinical trial with a special emphasis on anaerobic infections was designed for evaluation of the efficacy, safety, and patient tolerance of cefoxitin. Of the 35 patients who clinically evaluated, 19 had intrareproductive organ infections, 8 had extrareproductive organ infections and 8 had urinary tract infections. Twenty-nine out of the 35 (82.9%) responded satisfactorily to therapy with cefoxitin. The daily dose of cefoxitin for the 35 adult patients (ages ranged from 17 to 62 years) were 1--6 g. There were no adverse systemic reactions, nor was any renal or hematologic toxicity noted. Antibacterial activity tests demonstrated that cefoxitin was active against anaerobic bacteria, especially Bacteroides fragilis. Cefoxitin is thought to be the drug of choice in the treatment of obstetric and gynecologic infections.

To evaluate the penetration of imipenem/cilastatin sodium (MK-0787/MK-0791) into the female genital organ, concentrations of MK-0787/MK-0791 in antecubital vein blood, portio vaginalis, myometrium, endometrium, ovary and oviduct of patients who underwent simple hysterectomy and in the pelvic dead space exudate of patients who underwent radical operations for cancer of the uterine cervix were determined and analyzed using a two-compartment model. Concentrations at the end of a 30 minutes drip infusion of 500 mg/500 mg of MK-0787/MK-0791 were 48.38/52.69 micrograms/ml in plasma from the antecubital vein, 9.46/14.92 micrograms/g in the portio vaginalis, 14.10/9.79 micrograms/g in the myometrium, 6.47/11.42 micrograms/g in the endometrium, 14.72/13.30 micrograms/g in the ovary and 10.59/13.62 micrograms/g in the oviduct. Maximum concentrations of MK-0787 and MK-0791 in the pelvic dead space exudated were 10.66 micrograms/ml at 1.33 hours and 12.74 micrograms/ml at 1.15 hours after the start of the drip infusion, respectively. The concentration in plasma from the antecubital vein after an infusion of 1,000 mg/1,000 mg of MK-0787/MK-0791 reached 68.37/61.57 micrograms/ml at the end of a 60 minutes drip infusion, and the maximum concentration of MK-0787 in the pelvic dead space exudate was 20.02 micrograms/ml at 1.50 hours after the start of the drip infusion and that of MK-0791 was 14.90 micrograms/ml at 2.01 hours after the start of the drip infusion. MK-0787/MK-0791 was administered to 9 patients with obstetric and gynecological infections, and clinical efficacies were found to be excellent in 1, good in 6, and poor in 2 patients.