[Pharmacokinetic and clinical studies of cefodizime in the field of obstetrics and gynecology].

Cefodizime (THR-221, CDZM), a new antibiotic, was studied pharmacokinetically and clinically. The results obtained are summarized as follows: 1. Concentrations of CDZM in internal genital tissues were quite high after an intravenous infusion. 2. Clinical effects of the therapy with CDZM using intravenous infusion twice daily were evaluated in 1 patient with endometritis, 2 patients with pyometra, 1 patient with extragenital abscess and 1 patient with BARTHOLIN'S gland abscess. Clinical responses were good in all 5 patients. No side effects nor abnormal laboratory test values due to the drug were noted.

[Placental specific findings in twin pregnancies with hydramnion].

Eleven of 157 twin pregnancies were complicated with polyhydramnios. Chorionicity, vascular anastomosis and insertion of the umbilical cord were analyzed with relation to polyhydramnios. 1. Polyhydramnios was found commonly in monochorionic placentation. 2. Vascular anastomosis was found in 40% of monochorionic polyhydramnotic placentas, which was lower than the anastomosis of monochorionic non-polyhydramniotic placentas. 3. The placentas with hydramnios had a higher incidence of abnormal umbilical insertion (marginal or velamentous insertion). These data indicate that incompetent vascular connections between the two fetoplacental circulations may be the pathogenesis of polyhydramnios.

The mechanism of human placental urea transport: a study using placental brush border (microvillous) membrane vesicles.

To elucidate the mechanism of placental amino acid transport, the transport of amino acids into brush border membrane vesicles was investigated using brush border membrane vesicles (BBMV) separated from the human full-term placenta. 1. The transport of l-alanine and l-glutamine into the brush border membrane vesicles prepared from either early gestational placenta or full-termed placenta disclosed a typical overshooting phenomenon in the presence of H+ concentration gradient (extravesicular pH greater than intravesicular pH). 2. The H(+)-dependent overshooting transport of urea into the brush border membrane vesicles disappeared in the presence of H+ ionophore. 3. The initial velocity of H+ concentration gradient dependent uptake of urea into the brush border membrane vesicles was regulated by the saturation kinetics determined by the concentration of urea. The values of Km and Vmax, calculated as the kinetic parameters of urea transport by reciprocal plotting of the initial velocity of uptake and the concentration of urea, were 10.8 mM and 410 mumol/mg protein/10 sec, respectively. The above results indicate that a transport system which transports urea in exchange for H+ exists in human full-term placental microvillous membrane.

[The study on the human placental L-lactate transport mechanism (using placental microvillous membrane vesicles)].

To elucidate the human placental L-lactate transport mechanism, we investigated L-lactate uptake by microvillous membrane vesicles (MMV) prepared from full termed human placenta using the rapid filtration technique. 1. The transport of L-lactate into the MMV was not dependent on the Na+ electrochemical gradient (extravesicular greater than intravesicular). 2. The transport of L-lactate into the MMV was dependent on the H+ gradient (extravesicular greater than intravesicular) and this H+ dependent L-lactate uptake showed a tendency to overshoot. This overshoot disappeared with the addition of H+ ionophore (FCCP). 3. The initial rate of this H+ dependent L-lactate transport into the MMV exhibited saturation kinetics with respect to the L-lactate concentration: An apparent Km of 4.35mM and Vmax of 2.78n mol/mg protein/20sec were calculated. These results indicated that there existed a H+ and L-lactate transport system in human placental MMV.

The problem of hemoglobin switching in premature infants and IUGR infants.

Understanding the hemoglobin switching regulation mechanism in extremely premature infants is particularly important for understanding the extrauterine adaptation of the infants. In this study, we sought to identify factors influencing oxygen affinity in fetal blood and neonatal blood and obtained these results. (1) Aging is required for hemoglobin switching. (2) Switching in premature infants (27 to 32 weeks) is delayed at least 3 weeks in comparison with full-term infants. (3) A delay in the switching of fetal hemoglobin to adult hemoglobin was confirmed in IUGR (intrauterine growth retardation) infants. However, there is a compensatory increase in 2, 3-DPG for adaptation after birth. (4) A delay in 2, 3-DPG increase was observed in RDS (respiratory distress syndrome) infants, and oxygen affinity remained high.

An ovarian tumor of probable Wolffian origin with hormonal function.

In 1973, the histopathologic features of nine neoplasms with a distinctive appearance were reported under the term "female adnexal tumor of probable Wolffian origin." Although to date more than 40 cases of this disease have been reported in the literature, there have been only a few reports that the tumors might be endocrinologically active. We report on a hormonally active tumor of this type.

[The study on the platelet aggregation inhibition activity of placental brush border (the mechanism of platelet aggregation inhibition)].

To clarify the role of placental brush border in the regulation of placental microcirculation, we investigated the platelet aggregation inhibition activity of placental brush border membrane vesicles (BBMV) and obtained the following results. 1. There was very strong platelet aggregation inhibiting activity in placental BBMV. In the 20-40 micrograms/ml protein concentration, the BBMV almost completely inhibited the platelet aggregation induced by ADP, arachidonic acid and collagen, and in the 100-150 micrograms/ml protein concentration, the BBMV almost completely inhibited the platelet aggregation induced by ristocetin. 2. There existed a very strong ADP degrading activity (ADPase activity) in the placental BBMV. The platelet aggregation activity of ADP was completely lost when ADP was preincubated with the placental BBMV. 3. The placental BBMV inhibited platelet malondialdehyde (MDA) production. With the 20 micrograms/ml and 100 micrograms/ml protein concentrations of placental BBMV, 22% and 65% of platelet MDA production was inhibited respectively.

[A case report of an advanced ovarian cancer (stage T4) treated with a total amount of 1815 mg of CDDP].

A case is reported of a 34-year-old female who complained of an adult head-sized tumor in the pelvis and was treated with a high dose of CDDP. On the first look operation, it was found impossible to perform reduction surgery because of severe adhesion and peritonitis carcinomatosa. To introduce a high concentration of an anti-cancer agent into the tumor tissue, we administered CDDP intravenously, intraperitoneally and intra-arterially to the total amount of 1815 mg. After this high dose combination chemotherapy, a second look operation was performed and the tumor was seen to be reduced. The patient is now in remission and is being followed up as an out-patient. The clinical course of this case had decided for us which route would be the most effective and would have the least side effect, also, how much of a dosage can be administered as a maximum adoptive dose of an anti-cancer agent, and what kind of a second-line chemotherapy is effective against resistant cancer cells.