Severe Asherman's syndrome complicated with placenta increta conceived by intracytoplasmic sperm injection following hysteroscopic surgery.

Although severe Asherman's syndrome is a disease that may cause infertility, pregnancy and childbirth are possible by performing hysteroscopic surgery. However, the obstetrical outcome is not always satisfactory. We report a case where severe Asherman's syndrome occurred following a cesarean section. Hysteroscopic surgery was performed due to secondary infertility, and pregnancy was achieved through a subsequent intracytoplasmic sperm injection. At 23 weeks of gestation, the patient was hospitalized due to the threat of premature labor, and a cesarean section was performed at 29 weeks of gestation after pregnancy-induced hypertension occurred. It was determined to be abnormal adherent placentation such as placenta increta through intraoperative findings, and a cesarean hysterectomy was performed. The pathological diagnosis of the uterus was placenta increta. Due to the risk of complications from placenta increta in pregnancies following hysteroscopic surgery in patients with severe Asherman's syndrome, it is important to realize the high risk involved in such cases during the pregnancy course, and careful perinatal management should be required.

Mineralocorticoid receptor blocker eplerenone improves endothelial function and inhibits Rho-associated kinase activity in patients with hypertension.

Hypertension is associated with endothelial dysfunction and activated Rho-associated kinases (ROCKs). The purpose of this study was to evaluate the effects of the selective mineralocorticoid receptor blocker, eplerenone, on endothelial function and ROCK activity in patients with hypertension. The study was carried out over 48 weeks in 60 untreated patients with hypertension who were randomly assigned to eplerenone, nifedipine, and losartan groups. We evaluated the effects of each treatment on flow-mediated vasodilation (FMD) and ROCK activity in peripheral leukocytes. Eplerenone increased FMD and decreased leukocyte ROCK activity. Nifedipine decreased ROCK activity but did not alter FMD. Losartan increased FMD but did not alter ROCK activity. Hypotensive effects were similar in the three groups, as was nitroglycerin-induced vasodilation during the follow-up period. There were no significant differences between the groups with respect to other parameters. The study results show that eplerenone improves endothelial function and inhibits ROCK activity in patients with essential hypertension.

[Clinical evaluation of 2-mg granisetron tablet for nausea and vomiting induced by anticancer drugs including cisplatin].

The antiemetic effects on nausea and vomiting induced by anticancer drugs and safety of a 2-mg granisetron tablet were studied in cancer patients, particularly in the field of gynecology, who had been treated with anticancer drugs including cisplatin (CDDP) at 50 mg/m2 or more. The 1-mg granisetron tablet is already commercially available and used widely in clinical practice by oral administration of two tablets per dosage. In this investigation, the clinical efficacy, safety and usefulness of a 2-mg tablet, which can be taken more easily, were studied. The 2-mg granisetron tablet was judged to be "remarkably effective" or "effective" for nausea and vomiting in 22 (66.7%) of 33 patients. For safety, neither adverse experiences nor abnormal laboratory values were judged to be of clinical significance. The 2-mg granisetron tablet was considered "extremely useful" or "useful" in 22 (66.7%) of 33 patients. The above results confirmed the excellent antiemetic effect on nausea and vomiting induced by anticancer drugs including CDDP and the high degree of safety of a 2-mg granisetron tablet.

[Clinical evaluation of granisetron injection against nausea and vomiting induced by anticancer drugs including cisplatin].

The antiemetic effect and safety of granisetron injection on nausea and vomiting induced by anticancer drugs were studied in the patients treated with anticancer drugs including 50 mg/m2 or more of cisplatin (CDDP). Granisetron is already on the market, and drip infusion of granisetron at 40 micrograms/kg has been used widely in clinical practice. In this clinical investigation, a simpler administration method of its slow (30 to 60 seconds) intravenous injection at 40 micrograms/kg just before CDDP administration was used. The clinical efficacy, safety and usefulness against nausea and vomiting were investigated in 22 patients, and the study medication was assessed as "remarkably effective" or "effective" in 16 patients (72.7%). Neither adverse experience nor abnormal laboratory test value was reported. In the usefulness rating, the study medication was assessed as "extremely useful" or "useful" in 16 out of 22 patients (72.7%). The above results have shown that the slow intravenous injection of granisetron has an excellent antiemetic effect on nausea and vomiting induced by anticancer drugs including CDDP and a high degree of safety.

[Clinical results of UFT against ovarian carcinoma].

We carried out a phase II study on single oral administration of UFT in 17 patients with ovarian carcinoma. Two PR cases were observed out of 13 evaluable cases for a response rate was 15.4%. Side-effects, appearing in 10 of the cases (58.8%) were mainly anorexia (17.6%), stomatitis (17.8%), nausea/vomiting (11.8%), leukopenia (11.8%) and thrombocytopenia (11.8%), but they were not serious. UFT proved useful in the treatment of patients with ovarian carcinoma.

Biological-clinical significance of selective loss of HLA-class-I allelic product expression in squamous-cell carcinoma of the uterine cervix.

To determine possible correlations between the selective loss of HLA-class-I allelic forms on neoplastic cells and their biological-clinical characteristics, 89 squamous-cell carcinomas of the uterine cervix were evaluated immunohistochemically using monomorphic and polymorphic antibodies against HLA-A, -B, and -C molecules and analyzed clinico-pathologically. Four of the carcinomas exhibited a lack of detectable class-I heavy-chain expression associated with beta 2-microglobulin. In 19 of 42 HLA-A2-positive patients, tumor cells revealed loss of the HLA-A2 allelic product. Loss of HLA-B7 and/or 40 (B7/40) allelic product(s) on tumor cells was observed in 12 of 25 HLA-B7/40-positive cases. These alterations did not correlate with patient age, clinical stage (FIGO) of the disease, histological sub-type (WHO) or depth of cervical invasion. However, a statistically significant correlation was observed between lymph-node metastases and selective loss of HLA-B7/40 allelic product(s), but not with HLA-A2 allelic product on cancer cells of the primary lesion. Our results indicate that selective loss of certain HLA-class-I alleles on neoplastic cells can influence the nodal metastatic potential and suggest that these 2 class-I molecules may have different immune functions as restriction elements in T-cell-mediated cytotoxicity.

[Immunohistochemical study on the MHC class I antigen expression on squamous cell carcinoma of the uterine cervix].

Immunohistological analysis was performed to detect MHC Class I antigen expression on uterine cervical squamous cell carcinomas of 23 patients using a monoclonal antibody (W6/32) to recognize a monomorphic determinant of HLA-ABC and an antibody (MA2.2) to react only with cells typed as HLA-A2. The results were as follows. 1. In 2 of 23 cases examined, cancer cells lacked reactivity with W6/32, although normal epithelial cells and connective stromal cells surrounding cancer nests were clearly positive for the antibody in all cases. 2. Of the remaining 21 cases, fourteen cases were judged to be HLA-A2 positive, based on the obvious staining of the stromal cells with MA2.2. Of these 14 only 5 carcinomas were positive for HLA-A2, and the cancer cells in the other 9 cases failed to bind MA2.2. These data suggest that in most clinically diagnosed patients, cancer cells do not have their own MHC Class I products on their cell surfaces phenotypically, and this unique property may be related to the biological characteristic that permits cancer cells to survive and proliferate unrestrictedly in vivo, mainly escaping from the immune-surveillance system under cytotoxic T lymphocytes (CTLs), which need to recognize not only cancer-specific (associated) antigen(s) but also the self-MHC Class I products to kill the cancer cells efficiently.

Is immunotherapy for habitual aborters an immunologically hazardous procedure for infants?

Physical development and tests of immunologic function are reported from the first year of life for 13 infants born to mothers who were habitual aborters and who had undergone subcutaneous vaccination with their husband's lymphocytes. The mean weight of the infants at birth was 2,975 +/- 540 g, including one infant who was small for dates. Physical development parameters for the first year were all within normal range. Immunologic studies were performed at ages 0, 1, 3, 6, 9, and 12 months. The studies included the following: (1) serum levels of immunoglobulins and complement components; (2) the number of peripheral blood lymphocytes (PBL) and their subpopulations; and (3) proliferative responses by PBL against unrelated lymphocytes and some mitogens (pokeweed, phytohemagglutinin, and concanavalin A). All were normal when compared with studies of infants of nonimmunized mothers. These observations suggested that subcutaneous vaccination of women with their husband's lymphocytes did not result in any adverse effects on their infants' physical or immunologic development.

[Effect of oncofetal antigen-I (OFA-I) on lymphocyte response in pregnant women].

OFA-I, a membrane antigen on human malignant melanoma cells, was reported to be also found on a fetal brain tissue and to have a highly immunogenic effect on a pregnant woman. The aim in this study is to analyse an immunologic activity of OFA-I on in vitro response of lymphocytes from pregnant women. OFA-I was prepared from M-14 cells which are an in vitro cell line originating in a human malignant melanoma and purified by affinity column chromatography using the antibodies which were prepared from ascites of an embryonal carcinoma patient and exhibited anti-OFA-I activity in immune adherence test. The results obtained were as follows: No significant effect of OFA-I was found on PHA-induced lymphocyte response. A suppressive effect of OFA-I was observed on an unidirectional mixed lymphocyte culture (MLC) between a wife and husband when OFA-I was added at a concentration of more than 0.1 micrograms/ml. It was also suggested that the effect was attributable to inhibition in an initial phase of MLC. A suppressive effect of OFA-I was observed on Ig production of PWM-stimulated lymphocytes at a final concentration of more than 0.25 micrograms/ml. There was no significantly difference between the effect in pregnant and non-pregnant women. Furthermore, the effect was demonstrated to be mediated with macrophages in the culture system. From these findings, it was implied that OFA-I might play an important role in maternal immune recognition in the feto-placental unit.

[Clinical studies on the effect of imipenem/cilastatin sodium on infections in obstetrics and gynecology. Tissue concentrations and clinical effects].

Tissue transfer and clinical effects of imipenem/cilastatin sodium (MK-0787/MK-0791), a new carbapenem antibiotic, were studied and the following results were obtained. Penetrations of MK-0787 into uterine arterial blood and into pelvic dead space exudate were good. When MK-0787/MK-0791 was administered at a dose of 500 mg/500 mg by a 30-minute intravenous drip infusion, the peak level of MK-0787 in uterine arterial blood was 22.2 micrograms/ml, 30 minutes after the completion of the drip infusion. The peak level of MK-0787 in pelvic dead space exudate was 12.9 micrograms/ml at 2 hours and it dropped to 2.6 micrograms/ml at 6 hours. MK-0791 levels were similar to those of MK-0787. Penetrations of MK-0787 into tissues were also good. When MK-0787/MK-0791 was administered at a dose of 500 mg/500 mg by a 30-minute intravenous drip infusion, the level of MK-0787 was 2.2 +/- 1.1 micrograms/g in the oviduct, 2.7 +/- 2.1 micrograms/g in the ovary, 2.5 +/- 1.2 micrograms/g in the endometrium, 3.0 +/- 1.6 micrograms/g in the myometrium, 3.1 +/- 1.9 micrograms/g in the cervix uteri and 3.8 +/- 2.0 micrograms/g in the portio vaginalis at 1 hour after administration. These levels were reduced to halves, respectively, in approximately 2 hours. Four patients with intrauterine infections and 2 with vaginal stump infections were treated with MK-0787/MK-0791 at a daily dose of 1 g/1 g (500 mg/500 mg X 2). Good clinical and bacteriological responses were observed in 5 patients and causative organisms were eradicated in 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Studies of anti-lymphocyte antibodies, with special reference to anti-B cell antibodies in choriocarcinoma].

For the purpose of elucidation of the immunologic properties of anti-lymphocyte antibodies which appeared in sera of choriocarcinoma patients, HLA typing of lymphocytes, complement-dependent lymphocytotoxicity test (CT) and mixed lymphocyte reaction (MLR)-blocking assay with patients' sera were performed in 7 couples with the disease. The results obtained were as follows: HLA distribution characteristic of patients and their husbands was not observed. In 3 of 7 patients, their sera exhibited positive CT to their husband's lymphocyte. In MLR-blocking assay, a significant blocking effects (BE) with sera were detected in all patients. The serum BE tended to be sustained for 4 to 8 months even after the decline of serum beta-hCG into the negative range. It was also observed that a case in whom the BE was positive for a longer period of time in a state of remission eventually underwent recurrence. It was demonstrated that the BE and MLR was induced by serum IgG antibodies closely associated with surface antigens of the husband's B-lymphocyte. Consequently, it was strongly suggested that serum anti-lymphocyte antibodies immunologically reflect the tumour burden in choriocarcinoma patients.