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To investigate the self-priming effect of gonadotropin on the anterior pituitary glands, the response of serum gonadotropins to the "LH-RH two step test" (two step administration of 100 micrograms of synthetic LH-RH at a 60 minute interval) was studied in 20 women with normoestrogenic amenorrhea who were responsive to the progesterone test. The patients were divided into two groups according to the results of the clomiphene test. Blood samples were collected before LH-RH stimulation and 30, 60, 90, 120, 180 minutes after the first stimulation, respectively. The P1P2 ratio (2nd peak level/1st peak level) and delta 1 delta 2 ratio (delta 2/delta 1 = 2nd peak level-60 min. level/1st peak level-0 min. level) of LH and FSH in the clomiphene-positive group were significantly higher than those in the clomiphene-negative group. These ratios are regarded as the degree of the self-priming effect, and at least partially reflect the capacity for the synthesis of pituitary gonadotropins. The results demonstrate that the self-priming effect is more restored in the clomiphene-positive group than in the clomiphene-negative group, and the data also indicate that the analysis of the self-priming effect with the "LH-RH two step test" is useful in developing new diagnostic criteria on ovarian dysfunction.

A new operating hysteroscopic fiberscope consisting of soft and rigid parts (4.8mm outer diameter) was developed with the support of Fuji Photo Optical Company. The working part of the scope can be divided into three sections: A flexible soft front section, a rotary rigid middle section and a flexible self retained semirigid rear section. With these functional parts the intrauterine target can be approached directly to perform the following operations. 1. Directed intrauterine biopsy. Thirty-five patients diagnosed as having endometrial polyp (13), submucous myoma (8), endometrial hyperplasia (4), endocervical polyp (3), endometrial carcinoma (2) and others (5) underwent direct biopsy with hysteroscopic control. No cervical dilatation or anesthesia was necessary. 2. Transcervical recanalization. In six cases of proximal tubal occlusion, a ureteral catheter or a percutaneous coronary balloon angiocatheter was introduced into the tubal ostium of the obstructed side to resolve the occlusion successfully with concomitant laparoscopy. 3. Hysteroscopic chorionic villus sampling. Chorionic villus sampling was performed with a ureteral catheter under direct hysteroscopic control and ultrasound guidance in eighteen pregnant women at from seven to fourteen gestational weeks. In fifteen cases, the samplings were performed satisfactory. 4. Removal of a lost IUD. Three cases of lost IUD underwent hysteroscopic removal without difficulty. Our results have proved that this scope is a very useful tool for intrauterine operations.

To investigate the alteration of pituitary gonadotropin subunits in ovarian dysfunction by two step administration of LH-RH at 60 minutes interval, specific and sensitive radioimmunoassays of the subunits were utilized for this study. Blood samples were obtained from thirteen women of ovarian dysfunction and from fifteen normal women of subunits. The definition of delta 1 and delta 2 was as follows. delta 1(hormone release) = 30 (or 60) min value-0 min value. delta 2(hormone synthesis and release) = 90 (or 120, 180)-60 min value. delta 1 delta 2 ratio = delta 2/delta 1. Correlation was observed between the value of native gonadotropic hormones and the value of their subunits (LH-alpha and LH-beta) in normal women but no correlation was detected in delta 1 and delta 2 values in ovarian dysfunction. Thus LH-RH 2 step test suggest the possibility to differentiated pituitary function in both normal and abnormal subjects. The analysis of gonadotropin subunits was useful to develop new diagnostic criteria of ovarian dysfunction.

To clarify not only the releasing function but the self-priming effect of gonadotropins in the anterior pituitary gland, two step administration of 100 micro-grams of synthetic LH-RH at a 60 minute interval (LH-RH two step test) was investigated in 19 women with luteal insufficiency, 7 women in puerperium (3rd-10th postpartum) and 6 women immediately after first ovulation following spontaneous abortion (pregnancy 5-7 weeks). In the luteal phase, blood samples were drawn at 0', 30', 60', 90', 120' and 180' after first LH-RH stimulation for measurement of serum LH and FSH by radioimmunoassays. delta 1 standing for hormone release = 1st peak level -0' level. delta 2 standing for selriming effect = 2nd peak level -60' level. delta 1 delta 2 ratio = delta 2/delta 1. In the luteal insufficiency group, delta 1 was significantly higher and delta 1 delta 2 ratio was lower than those in the control group. In the puerperium group, delta 1 and delta 2 responses were not detected, suggesting marked depression of the pituitary function by pregnancy. In the aborted group delta 1 and delta 2 were similar to those in the control group, indicating rapid recovery of the pituitary function. This study demonstrated that the LH-RH two step test was useful in evaluating luteal function by measuring gonadotropins.

Pharmacokinetic and clinical studies on cefodizime (THR-221, CDZM) were carried out and the following results were obtained. Concentrations of CDZM in serum and uterine tissues were determined from 38 to 282 minutes after drip infusion of 1 g CDZM. CDZM reached peak level of 25.0 micrograms/g or higher in each tissue during a period of 38 to 83 minutes. Concentrations of CDZM in the dead space exudate after drip infusion of 2 g CDZM were also studied. At 240 minutes after injection, CDZM concentration in exudate reached a peak of 46.88 micrograms/ml. These levels far exceeded MICs of CDZM against major pathogens most often isolated in the field of obstetrics and gynecology. CDZM was administered to 7 patients with their diseases diagnosed as pelvic peritonitis (4 cases) or acute adnexitis (3 cases) at a dose of 2-4 g per day for 6-14. days. Clinical response was good in all cases. Transient elevation of liver function was noticed in 2 cases. No other adverse reactions were noted during the study.

Fundamental and clinical studies on imipenem/cilastatin sodium (MK-0787/MK-0791) were carried out and the following results were obtained. Concentrations of MK-0787 in plasma and uterine tissues were determined at 30 minutes to 390 minutes after the completion of an intravenous drip infusion of 500 mg/500 mg of MK-0787/MK-0791 sodium. Levels of MK-0787 in oviduct, ovary, endometrium, myometrium, uterine cervix and portio vaginalis were 5.1, 5.3, 4.2, 6.6, 5.2 micrograms/g and 6.0 micrograms/g, respectively, at 30 minutes after the completion of the infusion. These levels far exceeded the MICs of MK-0787 against major pathogens (Gram-negative rods and anaerobic bacilli) most often isolated in the field of obstetrics and gynecology. MK-0787/MK-0791 was administered by intravenous drip infusion to 11 patients, including 4 with pelvic peritonitis, 4 with adnexitis and one each with peritonitis, tubo-ovarian abscess, and endometritis, at a dose of 1 g/1 g-1.5 g/1.5 g per day for a period of 4 to 9 days. Clinical response was excellent in 2 and good in 9. No adverse reactions or abnormal laboratory findings were observed in any of the patients.

Hysteroscopy is a diagnostic method for intrauterine lesion. Most kinds of hysteroscope are rigid in type. Cervical dilatation and insertion of the trocar are necessary for hysteroscopy. These procedures can be very painful to the patient. Also subsequent blood clotting and injury to the endometrium may interfere with the diagnosis. With the help of Fuji Photo Optical Company, a new flexible hysterofiberscope (3.7 mm in diameter) was developed. The scope is divided into three portions; a front flexible part, a rigid middle part and a soft rear part. Cervical dilatation and anesthesia were not required even in a primiparous woman. The operator can observe the cervical canal, the uterine cavity and the tubal ostium very easily in a comfortable position. From Nov. 85 to Sep. 86 we carried out hysteroscopy in 411 patients with this new scope. The fluid medium which we used was a solution of 10% dextrose in water. The indications for hysteroscopy were abnormal uterine bleeding (187 cases), uterine myoma (80 cases), sterility (52 cases), post-transcervical surgery (22 cases) and others (70 cases). No complications were encountered during or after the procedure. The results were satisfactory. This new flexible hysterofiberscope has been proved an efficient tool for intrauterine diagnosis.

The pituitary gonadotropin response of synthesis and release to two step stimulation by 100 micrograms of LH-RH at 60 minutes interval was studied by radioimmunoassay of LH and FSH in normal menstrual cycling and menopause women and adult males. The blood samples were collected before LH-RH stimulation and 30, 60, 90, 120 minute after the first stimulation, respectively. The value of delta 1 was defined as either higher value at 30 or 60 minute minus the value at 0 minute. The value of delta 2 was defined as either higher value at 90, 120, or 180 minute minus the value of 60 minute. delta 1 Was explained as the release of pituitary gonadotropin and delta 2 standed for the release and synthesis of pituitary gonadotropin. delta 1 delta 2 Ratio was expressed as delta 2/delta 1 100%. If delta 2 was higher than delta 1, subsequently the value of delta 1 delta 2 ratio was larger than 100. When delta 1 was more than delta 2, then the value of delta 1 delta 2 ratio was smaller than 100. In normal menstrual women delta 1 of LH were as Preovulatory phase greater than Follicular phase greater than or equal to Luteal phase, delta 2 were as Preovulatory phase greater than Luteal phase greater than Follicular phase. The value of both delta 1 and delta 2 of FSH were Preovulatory phase greater than Follicular phase greater than Luteal phase. The delta 1 of serum LH of menopause women and adult males were higher whereas delta 2 of both serum LH and FSH of adult males were extremely low in value. delta 1 And delta 2 of serum FSH in menopause women showed higher values than those of others. delta 1 delta 2 Ratio of LH and FSH of both follicular phase and luteal phase were more than 100, indicating dominant pattern of synthesis of gonadotropin. The delta 1 delta 2 ratio of LH at preovulatory phase and of both LH and FSH in menopause women and adult males were smaller than 100, suggesting dominant pattern of release of pituitary gonadotropin. These dates suggest that our LH-RH two step test was more useful to clarify anterior pituitary function in terms of both synthesis and release of gonadotropin.

To clarify both the releasing function and the self-priming effect of LH-RH on gonadotropins of the anterior pituitary gland, two step administration of 100 micrograms of synthetic LH-RH at a 60 minutes interval (two step LH-RH test) was carried out in 29 women with luteal insufficiency, 10 women in luteal phase just after spontaneous abortion, 12 women in puerperium and 24 women with normal menstrual cycles. Native LH, FSH and their subunits were measured by radioimmunoassay and serum progesterone (P), estradiol (E2) and prolactin (PRL) were also measured before administration of LH-RH. By defining hormone release (1st peak level-0' level) as delta 1, self-priming effect (2nd peak level-60' level) as delta 2 and delta 2/delta 1 as delta 1 delta 2 ratio, in the luteal insufficiency group, especially in the cases with lower of serum P and E2, delta 1 was significantly higher and the delta 1 delta 2 ratio was lower than those in the control group. In the abortion group, delta 1 and delta 2 were similar to those in the control group, indicating rapid recovery of the anterior pituitary function. In the puerperium group (approximately 1 month after delivery), delta 1 was higher and the delta 1 delta 2 ratio was lower than those in the control group. This suggests that the puerperium is more or less similar to the period of luteal insufficiency. The results also indicate that the two step LH-RH test can be one of the useful methods for the study of luteal insufficiency in terms of the pituitary gonadotropin synthesis and release.