[Experimental and clinical studies of flomoxef in the field of obstetrics and gynecology. Representative Committee Members of the Research Team for Infections in the Field of Obstetrics and Gynecology].

Flomoxef (FMOX) has a broad antibacterial spectrum against Gram-positive and Gram-negative bacteria; especially its potent antibacterial activity against Staphylococcus aureus is a significant advantage that may not be found with other cephem compounds. In our determination of its antibacterial potency against various clinical isolates obtained from clinical materials (amniotic fluid, intrauterine secretions, exudates of the pelvic dead space) of patients with various infections, we obtained results representing specific features of this drug. From the results, the drug may be expected to produce an excellent effect in the treatment of various infections. Our study on drug concentrations in body fluids and genital tissues demonstrated a good transfer of this drug into various tissues; in every tissue examined, the drug administered by the usual method in the usual dose yielded a concentration exceeding MIC for principal pathogens, thus promising a good clinical response. Indeed a high clinical efficacy rate of 90.1% (good to very good responses) was obtained in a clinical trial involving 222 cases. Administration of the drug in 2 g quantity daily produced a high response rate of 92.8%. It was especially noteworthy that a good response was obtained in 30 of 32 cases (93.8%) in which other cephem compounds had failed. In evaluation of the bacteriological effect, furthermore, the drug showed an excellent rate of bacterial elimination. In conclusion, this drug is expected to be greatly useful in the light of its good transfer into genital tissues and its strong antibacterial activities against Gram-positive cocci, Gram-negative bacteria and anaerobes as well as against multiple bacterial infections predominating among women with genital infections.

Measurement of blood flow and oxygen consumption in the pelvic limb of fetal sheep.

In order to determine blood flow and oxygen consumption in the pelvic limb of fetal sheep, we applied the Fick principle of measurement of oxygen consumption in seven paired experiments in seven fetal sheep under normal conditions and after treatment with pancuronium bromide. Catheterization procedures, which minimized interference with the study limb circulation, avoided changes of catheter tip position during fetal movements,n and prevented collateral circulation to and from tissues not located in the pelvic limb, were utilized. Blood flow through the external iliac artery was measured by means of a transit time ultrasonic method. Six sample sets for oxygen content were drawn from the external iliac artery and vein during 45-min control period and repeated after neuromuscular blockade. Normal oxygen consumption under these experimental conditions was determined to be 20.7 +/- 1.9 (mean +/- SEM) mumole.min-1.100 g-1. Neuromuscular blockade caused oxygen consumption to decrease significantly (P less than 0.01) by 12% to 18.1 +/- 2.1 mumole.min-1.100 g-1 and decreased the average coefficient of variation from 15 to 8%. The data demonstrate that spontaneous skeletal muscle activity accounts for a significant amount of oxygen consumption, the level of which can vary widely over brief periods of time. These results suggest that such tissues with significant spontaneous changes in metabolic activity require repeated blood flow measurements with simultaneous determination of substrate arteriovenous differences to best describe metabolism under normal conditions.

[Fundamental and clinical studies on cefuzonam in the field of obstetrics and gynecology].

Fundamental and clinical studies on cefuzonam (CZON, L-105), a new cephem antibiotic, were carried out. The results obtained are summarized as follows: 1. Upon drip infusion of 1 g CZON, a good transfer of the drug into female genital organ was observed. The transfer of CZON into exudates of the pelvic dead space was also good. 2. Clinical efficacy of CZON was good in 1 case we tested. No side effect was observed.

The ontogeny of the mouse estrogen receptor: the pelvic region.

The appearance of estrogen receptors was examined during the course of fetal and neonatal development in the pelvic region of the mouse; 3H-diethylstilbestrol (DES) was administered via the maternal circulation to developing mice on days 4, 7, 10, 13, 14, 15, and 17 of gestation or to neonates on the day of birth. Localization of the ligand was monitored autoradiographically. The earliest appearance of estrogen receptors occurred in the mesenchyme around the genital ducts on day 13 of pregnancy. On subsequent days, estrogen-concentrating cells appeared in certain mammary-gland cells, connective-tissue strands, in perichondrium associated with specific developing bones, skin, interstitial tissue of the testis, in a sheath of cells surrounding the colon, and in the urethra. The significance of cells containing estrogen receptors in these locations is discussed in reference to a transplacental action of estrogens and the clinical ramifications of DES.

[Studies on antimicrobial concentration of clindamycin phosphate in serum, pelvic dead space exudate, and pelvic organs/tissues].

In women undergoing radical and total abdominal hysterectomy, clindamycin phosphate (CLDM-P) in a dose of 1,200 mg was administered by intravenous drip infusion over 1 hour and the drug concentrations in serum and pelvic dead space exudate, as well as pelvic organs/tissues, were determined over time. The following results were obtained: The serum concentration of clindamycin (CLDM) after intravenous infusion showed the peak value of 24.54 +/- 7.02 micrograms/ml at the end of infusion and then gradually decreased to 3.87 +/- 0.70 micrograms/ml in 6 hours. Concentration in pelvic dead space exudate, which was 2.82 +/- 3.90 micrograms/ml at the end of intravenous infusion, gradually increased to the peak value of 13.49 +/- 6.62 micrograms/ml in 1 hour. Two hours after infusion, the level of 12.43 +/- 5.56 micrograms/ml outstripped serum concentration. Continuously in excess of serum concentration, the exudate concentration gradually decreased to 6.65 +/- 2.27 micrograms/ml at 6 hours after infusion. Cubital venous serum concentration (16.36 +/- 3.68 micrograms/ml) was almost equal to uterine arterial serum concentration (16.36 +/- 4.05 micrograms/ml) of CLDM at uterine removal. In the pelvic organ/tissue concentrations, 15.71 +/- 3.86 micrograms/g in endometrium was highest, followed by 15.19 +/- 3.80 micrograms/g in oviduct, 14.80 +/- 3.52 micrograms/g in myometrium, 14.74 +/- 4.02 micrograms/g in ovary, 14.09 +/- 2.90 micrograms/g in portio vaginalis. The concentration was lowest (11.49 +/- 1.44 micrograms/g) in cervix uteri. Clinically, combined treatment with CLDM-P and ceftizoxime was excellently effective for endometritis induced by P. asaccharolyticus.(ABSTRACT TRUNCATED AT 250 WORDS)

[Preclinical and clinical studies on aztreonam in obstetrics and gynecology].

Aztreonam (AZT), a new monobactam antibiotic, was studied in obstetrics and gynecology with the following results. The tissue concentration of AZT in the female genital organs was relatively high at the portio vaginalis and the cervix uteri followed by at the ovary and the myometrium, but the distribution to the endometrium and the oviduct was a little poor. The concentration of AZT in the pelvic dead space exudate was highest at 2 hours after intravenous injection whereas it was highest at 5 hours after intravenous drip infusion. However, there was no significant difference in the concentration between intravenous injection and intravenous drip infusion and the distribution to the pelvic dead space exudate was relatively good. AZT was clinically administered to pyometra (3 cases), puerperal endometritis (3), adnexitis and endometritis (3), pelvioperitonitis (1), Bartholin's abscess (4) and purulent vulvitis (1), a total of 15 cases with an overall effective rate of 93.3%. AZT was microbiologically effective for Gram-negative bacteria such as E. coli and K. pneumoniae, but also effective for anaerobes and some Gram-positive bacteria, etc., for which MIC of AZT is high. With regard to safety of AZT, neither side effects nor abnormal laboratory findings were reported.

[Basic and clinical studies of aztreonam in the field of obstetrics and gynecology].

Aztreonam (AZT), a new monobactam antibiotic, was basically and clinically applied to the field of obstetrics and gynecology, obtaining the following results. The pelvic dead space exudate level of AZT after 30 minutes-intravenous drip infusion of 1 g attained the peak of 22.66 micrograms/ml at 1 hour from initiation of infusion and thereafter declined gradually, contrasting the peak of 34.38 micrograms/ml of the cubital vein at 30 minutes. Total of 13 cases comprising 4 with intrauterine infection, 5 with adnexitis and 4 with pelveoperitonitis were intravenously treated with AZT at a dose of 1 g twice daily. The overall clinical results were excellent in 3 cases and good in 10 cases. No side effects were observed in any of the cases treated with AZT.

[Fundamental and clinical studies on aztreonam in the field of obstetrics and gynecology].

The following results were obtained through the fundamental and clinical studies of aztreonam (AZT), a new monobactam antibiotic, in obstetrics and gynecology. Satisfactory tissue penetration was not recognized in 3-5 hours after intravenous injection of 1 g. However, the concentration was more than MIC for the majority of aerobic Gram-negative bacteria in intravenous drip infusion of AZT 1 g and in intravenous injection and intravenous drip infusion of 2 g. There was no difference of serum concentration of AZT between uterine arterial blood and cubital venous blood. AZT was administered by intravenous drip infusion to 2 cases of puerperal endometritis, 2 cases (the same patient) of vaginal wall abscess, 1 case of postoperative lymphocele infection and 1 case of infected ovarian cyst suspected, and it was effective for all of them. Neither subjective/objective side effects nor abnormal laboratory findings were noted in any case.

[Fundamental and clinical studies on aztreonam in the gynecological field].

Aztreonam (AZT), a new monocyclic beta-lactam antibiotic was studied on clinical efficacy for infectious disease in gynecological field. At about 80 minutes following intravenous injection of 1 g dose of AZT, it penetrated well into internal genital organs at therapeutic levels. Moreover it transferred very fast and enough into intrapelvic dead space exudate, and its level was kept still as high at 12 hours after administration. AZT was given to 20 women affected with gynecological infectious disease. The outcome of AZT therapy was as follows: effective in 5 out of 6 patients (83.3%) administered intravenously and in all of 14 patients (100%) received intramuscularly. Notable adverse effects or abnormal laboratory findings were not observed except 1 case of diarrhea and 2 cases of transient and slight elevation of serum CPK and transaminases. Based on these results, we may conclude that AZT is a highly effective and a very safe antibiotic for the treatment of infectious disease in gynecological field.

[Fundamental and clinical studies on aztreonam in the field of obstetrics and gynecology].

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%.

[In vitro activity and clinical evaluation of aztreonam in the field of obstetrics and gynecology].

Antimicrobial activity of aztreonam (AZT) against 231 clinical isolates in the field of obstetrics and gynecology was determined by agar-plates dilution method. Almost of all strains of E. coli (108 strains) tested were susceptible to the concentration of 0.20 micrograms/ml of AZT. Anaerobic bacteria, however, were less susceptible to this antibiotic than to cefazolin. The concentrations of AZT were determined in serum and pelvic tissue samples obtained at various intervals after 1 hour intravenous drip infusion with 1 g. The concentrations of AZT in pelvic tissues were maximal 9.3 micrograms/g at 57 minutes but less than 0.6 micrograms/g at 3 hours or more after injection. Clinical efficacy of AZT was evaluated in 6 cases consisted of two each with Bartholin's abscess and intrauterine infection and one each with post partum endometritis and acute adnexitis. Clinical efficacies were seen in 5 cases.

[Fundamental and clinical studies on aztreonam in the field of obstetrics and gynecology].

Fundamental and clinical studies on aztreonam (AZT), a new synthetic monobactam antibiotic, were performed and following results were obtained. Concentration of AZT was examined in serum, internal genital tissues and retroperitoneal fluid after a single intravenous administration of 1 g dose. The venous serum level of AZT was 114.0 micrograms/ml at 10 minutes after the administration, then decreased to 7.0 micrograms/ml at 3 hours. Since concentration of AZT in examined tissues showed wide variation, it was irrelevant to calculate transfer ratio. Concentration in retroperitoneal fluid made the peak of 40.0 +/- 22.6 micrograms/ml at 1 hour after the administration, then slowly decreased to 13.4 +/- 3.2 micrograms/ml at 6 hours. Judging from above data, the transfer of AZT to retroperitoneal fluid was favorable. In clinical trial, AZT was given to 17 cases with obstetrical and gynecological infections such as endometritis, uterine adnexitis, pelvic peritonitis, parametritis and lymphocystitis. The efficacy was evaluated as excellent in 2 cases, good in 12 and poor in 3, and efficacy rate was 82.4%. No side effects were observed in any of the cases. In laboratory findings, transient elevation of liver function in 2 cases and eosinophilia in 1 case were noticed.

[Fundamental and clinical studies on aztreonam in the field of obstetrics and gynecology].

Aztreonam (SQ 26,776, AZT), a new monobactam antibiotic, was fundamentally and clinically studied with the following results. Uterine and adnexal concentrations of AZT after intravenous injection of 1 g were highest 3 hours after administration in the ranges of between 18.6-23.4 micrograms/g 16.5-28.2 micrograms/g, respectively, and and rapidly decreased thereafter. Penetration of AZT into the pelvic dead space exudate was quickly recognized after intravenous injection of 1 g and its concentration 30 minutes after administration was 14.08 +/- 7.08 micrograms/ml and highest (22.35 +/- 5.85 micrograms/ml) 2 hours after administration. It gradually decreased to 8.50 +/- 2.07 micrograms/ml 6 hours after administration. Clinical effect was studied by administering 1-3 g of AZT twice a day for 3-16 days by intravenous drip infusion for 18 patients with various infections in the field of obstetrics and gynecology. Efficacy of AZT for 9 genital infection cases were excellent for 4 cases, good for 4 cases and poor for 1 case, with an overall efficacy rate of 88.9%. For 2 UTI cases, it was excellent for one case and good for the other, and for 4 pelvioperitonitis cases, excellent for 3 cases and good for 1 case. For 2 inflammation cases of the pelvic dead space, efficacy of AZT was excellent for both of them. With regard to side effect, there was only one rash case experienced. It was considered from the above results that AZT is sufficiently useful for the infections in the field of obstetrics and gynecology and also useful for various gynecologic surgery cases.

[Fundamental and clinical studies on aztreonam in the field of obstetrics and gynecology].

Fundamental and clinical studies were performed on aztreonam (AZT), a new antibiotic with single beta-lactam ring, with the following results. Following intravenous drip infusion of 1 g, transfer of AZT to the internal genital organs was found to be good. Transfer of AZT to exudate of pelvic dead space was also good. AZT was given to 6 cases, who had gynecological or obstetrical infectious disease. AZT was effective in the 5 cases out of 6, although it showed high MIC against bacteria isolated from the effective cases. The above results demonstrated that AZT was a safe and effective drug.

[Fundamental and clinical studies on aztreonam].

Aztreonam (AZT), a new monocyclic beta-lactam antibiotic, was studied on the transfer into intrapelvic tissues and on the clinical efficacy in the treatment of 19 cases of obstetrical and gynecological infections. The AZT levels were examined in the pelvic dead space exudate in 6 patients who received radical hysterectomy due to uterocervical cancer. The simulation curves for AZT were well performed after the decision of the pharmacokinetic parameters using the two-compartment model. Following 1-hour intravenous drip infusion of 1 g of AZT, the peak concentration of AZT in cubital venous blood was estimated 73.3 micrograms/ml at the end of infusion. The peak concentration of AZT in the pelvic dead exudate was estimated 18.6 micrograms/ml at 2.31 hours after infusion. Following intravenous 1-hour drip infusion of 1 g, the transferred level of AZT into uterine tissues was maintained at the effective concentration which means the excess level of the MIC against clinical isolates often observed in the field of obstetrics and gynecology. AZT was administered 2-4 g/day in 2 times a day by intravenous drip infusion for 60-90 minutes. The subjects were 19 patients with the following infections; pyometra (1), puerperal intrauterine infection (4), postoperative parametritis (4), pelvioperitonitis (2), purulent lymphocyst (1), acute salpingoophoritis (1), vaginal stump abscess (1), Douglas abscess (2), pelvioperitonitis + pyosalpinx (2), vulval abscess (1). Clinical efficacy was; excellent in 2 cases, good in 11 cases and poor in 6 cases. No notable side effect or abnormal laboratory finding was noted.

[Pharmacokinetics of aztreonam in peripheral venous serum, uterine arterial serum and intrapelvic female organs].

The concentrations of aztreonam (SQ 26,776, AZT, Squibb) in peripheral venous serum, uterine arterial serum and intrapelvic female organs were determined by bioassay, using the cylinder-plate diffusion method, in 27 women with simple total hysterectomy. With an intravenous injection of AZT 1 g, the maximum levels of peripheral venous serum and uterine arterial serum were 76.39 micrograms/ml and 76.38 micrograms/ml, respectively. Also, the biological half-life (T1/2) was 1.56 hours in peripheral venous serum and 1.54 hours in uterine arterial serum. The concentration in uterine arterial serum was more than 1.8 micrograms/ml at 8 hours after injection and maintained at a high level than the minimal inhibitory concentration necessary for most Gram-negative bacteria for at least 8 hours. The concentrations of AZT in female genital organs were kept higher than the minimal inhibitory concentration against E. coli at 4 hours after injection, and the ratios of the concentrations in uterine tube and endometrium to that in peripheral venous serum were 0.40 +/- 0.18 and 0.30 +/- 0.20, respectively. Since AZT is characterized by more potent antibacterial activity against Gram-negative bacteria and the minimal side effects, intravenous administration of AZT at 1 g or 2 g per day may be an adequate dose for infections of the female urogenital tract.

[Fundamental and clinical studies on aztreonam in obstetrics and gynecology].

Fundamental and clinical studies on gynecological use of aztreonam (AZT), a new monobactam, were performed with following results. Following the intravenous administration of 1 g dose of AZT, the transfer of AZT to pelvic dead space exudate was good, in which the concentration of that was 14.9 micrograms/ml (2 hours), 15.3 micrograms/ml (3 hours) after injection. The transfer of AZT to serum of umbilical cord and amniotic fluid was excellent. In a clinical trial, AZT was given to 5 patients with obstetric and gynecological infections. The clinical efficacy was evaluated as excellent in 1 case and good in the other 4 cases. No adverse effects were observed in any of the patients treated with AZT.

[Fundamental and clinical studies on cefpiramide in the field of obstetrics and gynecology].

Transfer of cefpiramide (SM-1652, CPM) to female genital organs was studied. CPM concentration was determined in the uterine artery, portio vaginalis, myometrium, ovary and oviduct of patients undergoing hysterectomy, and in the pelvic dead space exudate of patients undergoing radical hysterectomy due to uterocervical cancer. Data obtained were analyzed by three-compartment model. The maximum concentration at 1 hour after intravenous drip infusion of CPM in a dose of 1 g were 244.31 micrograms/ml in both the uterine arterial serum and uterine venous serum, 31.41 micrograms/g in the portio vaginalis, 32.99 micrograms/g in the myometrium, 31.67 micrograms/g in the ovary and 31.99 micrograms/g in the oviduct. The concentration in the pelvic dead space exudate reached to the maximum level of 5.32 micrograms/ml at 5.84 hours and thereafter decreased slowly. The clinical effect of CPM was examined in 6 patients with various female genital infections and found to be effective in all cases. Side effects and abnormal laboratory finding values were not observed at all.

[Fundamental and clinical study on cefminox in the obstetrical and gynecological field].

UNLABELLED: In order to assess clinical utility of cefminox (CMNX, MT-141), its transference into internal genital organ tissues and pelvic dead space was determined. In addition, transference of CMNX from maternal blood into fetal umbilical cord blood as well as into amniotic fluid was evaluated. In the clinical study, CMNX was administered in 4 cases. The following results were obtained. Transference into internal genital organ tissues; The concentration ratio of each tissue against serum concentration ranged from 25.3 to 42.7%, showing favourable transference as compared to other cephems. Transference into pelvic dead space; At 6 hours after intravenous injection of 1 g CMNX, its concentration in the pelvic dead space reached its peak of 38.8 micrograms/ml of the serum concentration, followed by gradual decrease. Transference into umbilical cord blood and amniotic fluid; Following intravenous injection of 1 g CMNX, its concentration in umbilical cord blood became almost similar to that of maternal blood at about 3 hours later, being 20 micrograms/ml. After that, it tended to decrease in accordance with the concentration in maternal blood. It appears that the drug persists for a more prolonged period in amniotic fluid. CLINICAL RESULTS: Clinically, CMNX was used in the treatment of 4 cases including 2 cases of lymphocystitis, 1 case of intrapelvic cellulitis and 1 case of postoperative wound abscess, and the results obtained were rated as excellent in 1 case, good in 2 cases and poor in 1 case with an efficacy rate of 75%. None of the cases treated experienced adverse reactions nor any laboratory abnormalities were observed.

[Pharmacokinetics and clinical studies on cefminox in the field of obstetrics and gynecology].

Cefminox (CMNX, MT-141), a new cephamycin antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained. The absorption and the penetration of CMNX into pelvic dead space exudate were good. The mean peak serum level after single intravenous injection was 190.8 micrograms/ml. The level in pelvic dead space exudate reached a peak of 36.6 micrograms/ml 4 hours after an intravenous injection of 1 g and 6.5 micrograms/ml after 12 hours, thus the level over MIC against main pathogenic organisms was maintained for a long time. CMNX was administered against gyneco-obstetrical infections such as intrauterine, intrapelvic, adnexal infections and postoperative wound infections with daily dose of 2 g and was effective in 11 cases out of 12 cases (91.7%), and 81.8% of bacteriological effect was obtained. No side effect was observed. From the above results the usefulness of CMNX in the field of obstetrics and gynecology was suggested.