Cesarean section and primary pulmonary hypertension: the role of intravenous dexmedetomidine.

Primary pulmonary hypertension is a fatal disease that frequently becomes evident in pregnancy. The management of pregnant women with primary pulmonary hypertension poses a number of difficult problems, especially where regional anesthesia is considered to be contraindicated. A 30-year-old woman who developed primary pulmonary hypertension at 23 weeks of pregnancy was transferred to our hospital. Systolic pulmonary artery pressure and plasma brain natriuretic peptide levels were markedly elevated. Nitric oxide inhalation and prostacyclin prevented the progression of cardiac failure and reduced both plasma brain natriuretic peptide and pulmonary artery pressure. Cesarean section was performed at 32 weeks under general anesthesia. A combination of nitric oxide, prostacyclin, nitroglycerin, and dobutamine were administered during surgery. Intravenous dexmedetomidine was specifically used during emergence and recovery from anesthesia. This provided effective pain relief and hemodynamic stability. Throughout the clinical course, brain natriuretic peptide levels was monitored and used as an indicator of cardiac failure.

Comparison between tube compensation and pressure support ventilation techniques on respiratory mechanics.

In the intubated patient, the presence of an endotracheal tube increases the work of breathing during spontaneous breathing. The tube compensation technique was developed as a new ventilator mode that can compensate for that additional the work of breathing. We investigated the respiratory parameters during the pressure support ventilation 0, 5, 10 cmH2O and tube compensation 100% modes of the Puritan Bennett 840 ventilator in ten postoperative patients who had undergone radical surgery for oesophageal cancer. Measurements were performed just before extubation. The tidal volume, respiratory rate and other respiratory parameters were measured with a Ventrak respiratory monitor, and the duty ratio, mean inspiratory flow, and rapid shallow breathing index were calculated. In particular, we performed a comparison between pressure support ventilation 5 cmH2O and tube compensation 100%, because pressure support ventilation 5 cmH2O is the usual ventilating mode before the extubation in our intensive care unit. The tidal volume of pressure support ventilation 10 cmH2O was significantly larger and the respiratory rate was significantly lower than the other three modes. There was no significant difference in the minute volume, tidal volume, and respiratory rate between pressure support ventilation 5 cmH2O and tube compensation 100%. The duty ratio of pressure support ventilation 10 cmH2O was significantly smaller than the other three modes. There was no significant difference in the duty ratio and rapid shallow breathing index between pressure support ventilation 5 cmH2O and tube compensation 100%. It was concluded that the assist levels of pressure support ventilation 5 cmH2O and tube compensation 100% were almost equal for clinical purposes.

[Progress of contraceptive methods--OC and IUD].

In Japan, most couples use traditional methods, with about 80% relying on the condom and a further significant proportion on the rhythm method. In fact a combination of both methods is common among married couples. The oral contraceptives have the following advantages: Reversibility, simple and easy to use, coitally independent, no skill or knowledge required for its use, high acceptability, no pain or discomfort at use, self-administration, while they have the following disadvantages: Inadequate during lactation, sustained motivation in the female side required, clinical contraindication exists, possible side-effects such as nausea, vomiting, breast tenderness, weight gain, questionable possibility of serious side effects such as hypertension, thromboembolic diseases etc., medical supervision and follow up required, expensive cost. The use of the steroidal preparations for contraceptive purpose in Japan awaits official approval. Under present regulations, it is not illegal for the physicians to prescribe the pill, and currently six preparations are available and all contain 50 microgram of estrogen. The reduction in the estrogen and progestogen content of the pill did not appreciably compromise contraceptive potential while untoward effects were considerably lowered. The development and use of the new progestogen also contributed to minimize the possible side effects. Efforts are now being directed at a pill which minimizes metabolic change, decreases the incidence of breakthrough bleeding or spotting, without compromising efficacy. It is with these goals in mind that the multi-phasic pills have been developed in the belief that many of the undesirable side-effects can be circumvented while maintaining almost 100% conception control.(ABSTRACT TRUNCATED AT 250 WORDS)

Succinic acidemia: a new syndrome of organic acidemia associated with congenital lactic acidosis and decreased NADH-cytochrome c reductase activity.

Two siblings with succinic acidemia, a hitherto unreported organic acidemia, were investigated. Succinic acidemia, lactic acidosis and respiratory distress were observed in one of the siblings, who died 37 days after birth, and succinic acidemia was also detected in the next sibling at the fetal stage. NADH-cytochrome c reductase activity was significantly low in both cases and NADH-ferricyanide reductase activity was also low in the fetal case, suggesting a complex I deficiency of the electron transport system in the mitochondrial membrane.

[Future tasks related to contraception].

PIP: Japan's contribution to the research and development of contraceptives remains insignificantly small despite the fact that Dr. H. Nakajima was appointed general secretary of WHO in 1988. Unlike other industrialized nations Japanese couples still rely on such traditional methods of contraception as condoms (82.1% in 1986) and Ogino Method (11.3% in 1986). Relatively high tolerance of abortion among Japanese men and women, passive attitude toward sex and contraception among young Japanese women and ignorance of contraception among Japanese men all contribute to this peculiar pattern of birth control practice. IUD, which was introduced in 1930, was no legalized officially till 1974. Family planning movement legacy of post-WWII Japan, is conducted from the standpoint of maternal-child health, for the prevention of unwanted pregnancy and resulting abortion. WHO's Special Programme of Research, Development and Research Training in Human Reproduction which was started in 1972, is described in part. Task Force on Long-acting Systemic Agents for Fertility Regulation explores long-acting agents and alternative to oral contraceptives such as injections and cervical rings with progesterone. Task Force on Vaccine for Fertility Regulations explores vaccines which paramedical staff can readily give in developing nations where doctors are scares. Task Force of Post-ovulatory Methods studies effects of combined RU-486 and prostaglandins. Task Force on Plants for Fertility Regulation studies pharmacological effects of chemical substances extracted from plants in great apes. Task Force on Diagnosis and Treatment of Infertility gears toward United States, where birth rate and population increase are high but frequency of infertility is also high. Japanese participation in these task forces is yet to see.^ieng

[Bestrabacil: a possible target-oriented anticancer agent].

Bestrabucil, the benzoate of an estradiol-chlorambucil conjugate, was initially developed as a target-oriented anticancer agent for breast cancers with positive estrogen receptors, by conjugating a tumoricidal agent, chlorambucil, to a vehicle, estradiol. Further studies, however, revealed that regardless of the presence of estrogen receptors, bestrabucil selectively accumulates in malignant tumor cells. The unique feature of bestrabucil, selective affinity to tumor cells, was demonstrated in in vitro and in vivo studies. Significantly larger amounts of 3H-bestrabucil accumulated in malignant cells (3T3-SV40 transformed) than in normal cells (3T3). In vitro inhibition effects of bestrabucil on cell growth was observed only in malignant cells. Selective accumulation of bestrabucil in malignant tumor tissues was also demonstrated in in vivo experiments. After a single oral administration of 100 mg/kg of bestrabucil to female Wistar rats bearing Walker 256 carcinoma, bestrabucil accumulated significantly occurred in tumor tissues with little or no accumulation in normal tissues and blood. Anti-tumor effects and toxicities of bestrabucil and chlorambucil, were compared using Walker 256 carcinoma. Bestrabucil exerted its antitumor effects with little change in leucocyte counts in the peripheral blood, whereas chlorambucil showed significant side effects. Finally, selective accumulation of bestrabucil in malignant tumor tissues, was demonstrated clinically. Tumor specimens obtained during the operation of patients with various types of cancer, 24 hours after oral administration of 100 mg of bestrabucil, contained significantly larger amounts of bestrabucil compared with adjacent normal tissues. Clinical trials of bestrabucil are being carried out at present. Bestrabucil seems to be a promising target-oriented anticancer agent and deserves further investigation.

Antipyrine disposition in relation to lowered anticonvulsant plasma level during pregnancy.

The authors studied antipyrine disposition before and after delivery in 4 epileptic women whose anticonvulsant plasma level per dosage ratio was lowered during pregnancy, and compared the results to those found in nonpregnant women undergoing antiepileptic treatment (N = 6) and healthy women (N = 6). The antipyrine clearance at term (0.53 +/- 0.11 ml/min/kg, mean +/- SD) was lower than it was early during puerperium (0.70 +/- 0.14 ml/min/kg, P less than .05) and approximately 3 months after delivery (1.14 +/- 0.26 ml/min/kg, P less than .01). The antipyrine clearance in nonpregnant epileptics (1.17 +/- 0.44 ml/min/kg) was comparable to that found 3 months after delivery, whereas it was significantly (P less than .01) higher than that found in healthy women (0.47 +/- 0.02 ml/min/kg). These observations suggest that the fall during pregnancy of anticonvulsant plasma concentrations relative to dosage is not attributable to the enhanced oxidative process of hepatic drug metabolism.

Inhibition of leukocyte migration in agar by soluble extract from a human ovarian carcinoma cell line.

A soluble membrane extract was prepared by a hypotonic extraction method from a cultured cell line, CKS, derived from serous cystadenocarcinoma of the ovary. The leukocyte migration inhibition assay in agar was used to determine the cell-mediated immune response with this extract in patients with ovarian carcinoma in comparison with patients with other benign or malignant tumors and normal healthy subjects. With 100 micrograms protein/ml of the extract, leukocytes from 15/25 patients with ovarian carcinoma showed positive response, whereas 5/30 patients with benign tumors, 2/23 patients with non-ovarian carcinomas, and 0/13 normal healthy controls did so. These findings suggested that the soluble membrane extract from the CKS cells specifically inhibited migration of leukocytes from patients with ovarian carcinoma. There was a tendency that the stage III or IV patients responded to the extract more frequently than the stage I patients irrespective of histological type of ovarian carcinoma. The migration inhibition assay with a basic encephalitogenic protein (100 micrograms protein/ml) from bovine brain was performed simultaneously with the ovarian cancer extract. One of 20 patients with ovarian carcinoma, 1/29 patients with benign tumors, 1/22 patients with non-ovarian carcinomas, and 0/13 normal healthy controls responded positively. Therefore, cross-reactivity between the basic protein and tumor-associated antigens could not be demonstrated in the present study.

[Experimental and clinical studies of cefmenoxime in the field of obstetrics and gynecology].

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.

Placental transfer of anticonvulsants (phenobarbital, phenytoin, valproic acid) and the elimination from neonates.

In six full-term newborn infants born to epileptic mothers, the cord-to-maternal concentration ratios of anticonvulsants and the plasma disappearance of the drugs transferred across the placenta were studied. The respective mean +/- SEM values for the ratio of the cord-to-maternal blood concentration were: 0.95 +/- 0.05 (n = 5) for phenobarbital (PB), 0.97 +/- 0.04 (n = 3) for phenytoin (PHT), and 1.71 +/- 0.23 (n = 4) for valproic acid (VPA). The disappearance from the plasma of neonates showed a discernible two-component (initially slow and then fast) curve for all cases with PB, for one with PHT, and for two with VPA. Half-lives calculated from the terminal elimination phase were: 74.0 +/- 8.8 hours for PB (n = 5) and 26.8 +/- 4.8 hours (n = 4) for VPA. The half-life value of PB observed in this study was found to be shorter than that observed postnatally in the previous reports, while that of VPA was two to three times as long as that reported from children or adults, but shorter than that from a neonate in the literature.

Interruption of pregnancy with vaginal suppositories containing 16,16-dimethyl-trans-delta 2-prostaglandin E1 methyl ester.

A new synthesized Prostaglandin E1 analogue, 16,16-dimethyl-trans-delta 2-Prostaglandin E1 methyl ester, has been shown to be effective in termination of 1st and second trimester pregnancy following vaginal administration. Suppositories, each containing 1 mg Prostaglandin E1 derivative, were administered five times to each of fifty pregnant women of five to twenty gestational weeks at three-hourly intervals. The procedure was clinically effective in 86% of the patients resulting in 56% complete and 30% incomplete abortions. The cervix of all patients was dilated up to 7 mm in diameter at the second insertion of the suppository. Vaginal bleeding and lower abdominal pain not requiring sedation were observed in all patients. Diarrhea (42%), vomiting (6%), and fever (4%) were the most common side effects. The Karyopyknotic Index of the vaginal smear increased significantly (p less than 0.01) twelve hours after the initial insertion. The superficial cells of the cervix gradually degenerated during the termination procedure.

PIP: 16,16-dimethyl-trans-delta2-prostaglandin El methyl ester, a newly synthesized prostaglandin E1 analogue (PGE), was evaluated to determine the clinical and cytological characteristics and efficacy of vaginally administered PGE for termination of 1st and 2nd trimester pregnancies. 50 16-45 year-old, 5-20 week pregnant, women were studied. Suppositories, each containing 1 mg of PGE derivative, were administered 5 times to each woman at 3-hour intervals. The procedure was clinically effective in 86% of the patients, resulting in 56% complete and 30% incomplete abortions. Cervix of all patients was dilated up to 7 mm in diameter at the 2nd insertion. Vaginal bleeding and lower abdominal pain, not requiring sedation, were observed in all patients. Vaginal smear karyopyknotic index increased significantly (P .01) 12 hours after the initial insertion. Superficial cells of the cervix gradually degenerated during the termination procedure. No significant difference in cervical dilatation was observed between parous and nonparous study participants.