Efficacy and safety of labour induction in patients with a single previous caesarean section: a proposal for a clinical protocol.

PURPOSE: To evaluate the efficacy and safety of induction in women with a single prior Caesarean section. METHODS: This was a cohort study in which we included all singleton pregnancies in patients with a single prior Caesarean who delivered between 2007 and 2012. Methods of induction were ocytocic infusion plus amniotomy (if Bishop score ≥6) or insertion of a Foley catheter (Bishop <6). RESULTS: Of the 2,075 patients included, 806 (38.8 %) had an elective repeat Caesarean, 1,045 (50.4 %) went into spontaneous labour, 89 (4.3 %) were induced by artificial rupture of the membranes and infusion of ocytocics and 135 (6.5 %) were induced using a Foley catheter. Rates of vaginal delivery were 79.2, 79.8 and 43.7 %, respectively. Six cases of uterine rupture were reported in the group of patients who went into spontaneous labour. There was no difference between groups with regard to neonatal morbidity. On multivariate analysis, risk factors for Caesarean delivery were macrosomia (OR 2.04, 95 % CI 1.31-3.18) and induction by Foley catheter (OR 3.73, 95 % CI 2.47-5.62); protective factors were previous vaginal delivery (OR 0.41, 95 % CI 0.29-0.57) and cervical dilatation (OR 0.84, 95 % CI 0.78-0.91). CONCLUSIONS: Uterine induction after a single Caesarean section with ocytocic infusion and amniotomy where the cervix is favourable does not appear to entail any significant added risk in terms of maternal or foetal morbidity. Foley catheter induction is a reasonable option if the cervix is not ripe.

Intracellular localization of aflatoxin B1 in rat and human livers.

Hepatocytes of rats fed with a diet containing Aflatoxin B1 show a strong primary fluorescence both in cytoplasm and nucleus. This fluorescence does not exist in control animals fed either with nonfluorescent carcinogens or fluorescent molecules devoid of carcinogenicity. In this work, the primary fluorescence is likely to be due to the presence of aflatoxin B1 (and/or its fluorescent metabolites) in the liver. The same fluorescent microscopy technique was applied to human liver fragments originating from countries known for the high risk of primary liver cancer (Zaire, Uganda). A fluorescence similar to that observed in rat livers was demonstrated. This fluorescence may be due to the occurrence of aflatoxins in the liver.

Aflatoxin, viral hepatitis and primary liver cancer.

Thirty-eight cases of primary liver cancer (PLC) from the Department of Pathology, Charles University, Hradec Kralové were investigated. The viral hepatitis HBsAg antigen was found in the sera of 8 of the 38 patients. Radioimmunoassay demonstrated aflatoxin in 27 of 34 cases. Fluorescence microscopy revealed a fluorescence characteristic of aflatoxin and its fluorescent metabolites in the peritumoral tissue and the tumor for all of the cases studied. This study emphasizes the increasing incidence of PLC over the last 15 years. In addition, this type of cancer now appears to develop in a different manner: reduction in the number of cases with cirrhosis, progressive rise in the number of women affected, and occurrence of PLC in children and adolescents. These observations tend to indicate that aflatoxin might play a significant role in the genesis of PLC.

Ovarian function during aflatoxin B1-induced hepatocarcinogenesis in the rat.

Study of the endocrine status, which is often disturbed during hepatocarcinogenesis, is particularly valuable because gonadal function and hormone production regulate hepatic metabolism of the carcinogen. Sex steroids can even promote carcinogenesis. After aflatoxin B1 induction of liver carcinogenesis in adult female Sprague Dawley rats, livers were examined by histology, fluorescence microscopy of the carcinogen and its metabolites, and alphafetoprotein (AFP) assays. Ovarian activity was assessed, and both progesterone and estradiol levels were determined. Administration of a diet containing 10.32% total protein plus 2 ppm aflatoxin B1 was observed to prevent development of liver tumors during the 300 day study period. This finding is especially interesting for the study of populations suffering from malnutrition and exposed to dietary carcinogens. Under study conditions, aflatoxin B1 did not cause elevation of AFP levels, as occurs with other hepatotoxic substances. This absence of a rise in AFP despite liver alterations explains the surprising lack of ovarian modifications. In other experiments, AFP has been shown to cause genital function blockade which leads to reduced levels of hormonal promoters, for example during N2 fluorenylacetamide carcinogenesis. The endocrine reaction implicated in the development of tumors during carcinogenesis thus appears closely related to the nature of the carcinogen, AFP production, and the composition of the diet.

Effects of alphafetoprotein on isolated mouse oocytes.

The supposition of an effect of alphafetoprotein (AFP) on female germinal cells is put forward. The spontaneous in vitro maturation of adult mouse oocytes is significantly inhibited when mouse AFP replaces albumin in culture medium. Furthermore, the very unusual degenerative appearance of the cells subjected to AFP seems to indicate that this meiotic inhibition is linked to a premature degeneration of the oocytes rather than to a blockage of the cells at an earlier stage of maturation. Accordingly AFP, perhaps through its ligands, may play a role in reducing the number of gonocytes during fetal and immediate post-natal life rather than in stopping oocyte meiosis at the diplotene stage.

Alphafetoprotein and atretic follicles in the ovary of the pregnant rat.

Previous experiments have been conducted concerning the role of alphafetoprotein in genital system blockade in several cases: during adult rat N2-fluorenylacetamide hepatocarcinogenesis, after alphafetoprotein injections into normal adult female rats, during fetal life, and during postnatal and prepuberal development. In these conditions, alphafetoprotein is present at high plasma levels, and the normal cyclic ovarian function is stopped or nonexistent. The degenerating oocytes observed in the ovaries are often AFP-positive by histo-immunolocalization. Pregnancy corresponds to a physiological state in which alphafetoprotein levels are high while the gonadal activity is not characterized by ovulatory cycles. In order to assess our hypothesis, alpha-fetoprotein was studied in the ovary of pregnant rats from day 18 to 21 of gestation by an immunofluorescent technique, and alpha-fetoprotein was assayed in plasma samples. The results of this work show that, during pregnancy, follicular maturation is blocked at the antral stage, and the follicles contain degenerating oocytes that are AFP-positive in immunofluorescence. In conclusion, we suggest that the alpha-fetoprotein produced by the fetal liver and the yolk sac is disseminated in the amniotic fluid and passes through the placenta, and then reaches the ovarian follicles and the oocytes. The possible role of alphafetoprotein in follicular atresia is discussed.

[Effect of alpha-fetoprotein on isolated mouse oocytes]. / Effet de l'alpha-faetoprotéine sur les ovocytes de souris isolés.

Data are presented which indicate a possible action of alpha-fetoprotein (AFP) on female germinal cells. The in vitro maturation of mature mice oocytes was significantly inhibited when mouse AFP replaced albumin in the culture medium. In addition, the degenerative aspect of oocytes cultured with AFP seemed to indicate that this meïotic inhibition was caused by a premature degeneration of oocytes rather than by a blockage at a specific stage of maturation. Thus AFP, perhaps through its ligands, may play a role in the reduction of germinal cells during fetal and immediate post-natal life rather than in the arrest of meïosis at the diplotene stage.

[Alpha-fetoprotein and blockade of the sexual cycle]. / Alpha-foetoprotéine et blocage du cycle génital.

During chemical hepatocarcinogenesis by N-2 fluorenylacetamide in adult female Rats, vaginal cycle alterations were observed after 30 days of carcinogenic diet, and a blocking at the metestrus stage appeared from the 70th day. This may be explained by the very low serum progesterone level prevailing after the 50th day. An important drop in ovary weight was also noticed; together with the blocking of follicular maturation and ovulation leading to a marked follicular atresia. Simultaneously, alpha-fetoprotein (AFP) seems to interact in the lowering of progesterone level, and AFP was found ten times higher in the serum of treated animals than in controls. AFP was localized in degenerative oocyte cytoplasm by immunofluorescence in the treated animals, but not in the controls. In conclusion, a blocking role of AFP on genital cycles and a relationship between AFP and follicular atresia are suggested.

Aflatoxin and Reye's syndrome.

This study indicates the association of a mycotoxin (aflatoxin B1) with Reye's syndrome. The presence of aflatoxin B1 in livers from 4 girls and 1 boy aged from 3 to 11 months was detected using two different techniques: a) direct chemical titration of aflatoxin B1 in liver extracts; and b) fluorescence microscopy of unstained liver sections. Our results suggest the existence of acute intoxication by aflatoxin in these children.

Immunolocalization of alpha-fetoprotein in the ovary and hypophysis of immature female rats.

Alpha-fetoprotein (AFP), an oestrogen-binding protein, has been localized in the ovary and hypophysis of prepuberal rats. In the ovary, AFP was localized in secondary follicles, its distribution being limited to the liquor folliculi and the zona pellucida. In the hypophysis, AFP was only found in blood vessels. The intra-ovarian localization of the protein is consistent with our previous hypothesis that AFP might act as a regulator of ovarian activity by decreasing the local free oestradiol level.

Sex steroid hormones levels and testicular activity during hepatocarcinogenesis by N-2-fluorenylacetamide.

During hepatocarcinogenesis by N-2-fluorenylacetamide, the hormonal status of male Sprague-Dawley rats is modified. The testes present a reduced activity which is evidenced by a decreased spermatogenetic activity accompanied by a drastic decrease of the plasma testosterone level. In contrast, plasma progesterone and estradiol-17 beta levels were not modified despite the 80 fold augmentation of alpha-fetoprotein, an estrogen binding protein synthesized during liver carcinogenesis.

Thyroid activity during hepatocarcinogenesis by N-2-fluorenylacetamide in the male rat.

During chemical hepatocarcinogenesis by N-2-fluorenylacetamide, the hormonal status of male Sprague Dawley rats is modified. The histological study of the thyroid gland demonstrates a decreased activity evidenced by an augmentation of the follicle size and a reduced size of follicular epithelium. The level of T3 and T4 reflects in part this decreased activity. Comparison with female rats treated in the same conditions shows an opposite effect of N-2-fluorenylacetamide. Indeed in the female, the thyroid gland presented an hyperactive state accompanied by a drastic decrease of serum T3 and T4. This difference in thyroid activity might take an important part in the mechanism responsible for the sex difference in liver cancer induction by N-2-fluorenylacetamide.

Role of alpha-fetoprotein (AFP) in the regulation of ovarian activity during hepatocarcinogenesis and post-natal development.

N-fluorenylacetamide produces an augmentation of serum AFP which is accompanied by a drastic decrease of ovarian activity. A passive augmentation of the AFP level of adult rats, produced by injection of this protein provokes the same phenomenon: i.e. a decrease of follicular maturation, a decrease number of corpora lutea and finally a drop in the plasma progesterone level. The study of ovarian post-natal development shows that ovarian maturity occurs on the 35th day of life when AFP level reaches its adult serum concentration. These facts support the hypothesis that AFP plays a role in the regulation of ovaries during the sexual maturation of the female rat.

In vivo regulation of ovarian activity by alpha-fetoprotein.

Adult female rats, each injected with 760 microgram alpha-fetoprotein (AFP) weekly, presented after the third week a decrease of ovarian activity evidenced by a decreased number of maturing follicles, corpora lutea, and a drop in ovarian weight. The level of progesterone was low and agreed with the decreased number of corpora lutea. Conversely, total and free estradiol-17 beta levels remained normal despite the known ability of AFP to bind estrogenic hormones. A regulatory role of AFP during the postnatal stage of sexual maturation is proposed.

The first abortion - and the last? A study of the personality factors underlying repeated failure of contraception.

The causes leading to a second abortion were outlined in a psychological study comparing 30 women expecting a second abortion with 29 women who had successfully prevented conception after a first abortion. It was found that both groups improved their contraceptive practices after the first abortion. However, while the latter group continued with their improved practices, the former group went back to the earlier inefficient or non-existent contraceptive behavior. The inability to improve contraception in the long run was not related to differences in educational level or knowledge about contraceptive techniques but to the developmental level of personality structures. The women expecting their second abortion rated lower in control of impulsivity, emotional balance, realism, self-esteem and stability of life as well as capacity for more integrated personal relationships. The differences in personality development and consequently in the capacity for long-term contraception were found to be due to growth conditions in childhood.

[Physiological role of alpha-fetoprotein. Effect of the injection of purified AFP on the ovarian activity of the adult female rat]. / Rôle physiologique de l'alpha-faetoprotéine (AFP). Effet d'injection d'AFP purifiée sur l'activité ovarienne du Rat femelle adulte.

Alpha-fetoprotein injected in normal adult female Rats produced a decrease in ovarian activity. The histological study of the ovaries showed that the number of maturing follicles as well as the number of corpora lutea were lowered in AFP-treated Rats, but not in albumin-treated control animals. The serum level of progesterone was also largely decreased by AFP injections. A possible role of AFP in the regulation of the ovarian activity during pregnancy and post natal sexual development is proposed.

Intrahepatic polyamine levels during rat liver carcinogenesis induced by N-2-fluorenylacetamide.

During a period of 200 days, the chronological changes of polyamine levels (putrescine, spermidine and spermine) were observed in the liver of adult female Sprague Dawley rats submitted to hepatocarcinogenesis by N-2-fluorenylacetamide (FAA). Three groups of 70 rats each were used: (1) Control 1: normal diet; (2) Control 2: low protein and low riboflavin diet; and (3) EXPERIMENTAL: 0.06% FAA added to the diet. No significant differences were noted for tissue levels of the three polyamines when the two control groups were compared. In contrast, considerable variations of these molecules were observed as a function of time in the FAA treated group: (a) an early and constant rise was seen in putrescine, with 3 maxima at days 10, 60 and 150. This last peak was the highest: 25 +/- 6 nmol/g (8 times the value for the controls at this time), and coincided with the appearance of cancerous lesions. (b) While spermidine levels varied during the experiment, no significant differences were noted in comparison with the control groups. Mean levels (nmol/g) were: 535 +/- 108 Control 1; 552 +/- 95 Control 2; 633 +/- 160 FAA-treated group. (c) Spermine levels were significantly lowered, with 3 minima corresponding to the putrescine maxima. The lowest minima was observed on day 60: 114 +/- 67 nmol/g, i.e., 4 times lower than the controls. This work shows that polyamine metabolism is profoundly modified during chemical carcinogenesis, but the possible effect of polyamines on tumorigenesis itself cannot be assessed at this point since modifications of polyamine levels are probably also associated with phenomena of liver necrosis and compensatory tissue proliferation observed during the experiment.

Characterization of aflatoxin BI (AFB) in human liver cancer.

The occurrence of aflatoxin BI in human liver cancers was evidenced by thin layer chromatography followed by spectrophotometry of the chloroformic extract of tissue samples. Microscopic slides obtained from the same samples were also examined by direct fluorescence microscopy. In five cases, the chemical identification of aflatoxin BI was associated with the demonstration of a strong blue fluorescence of the tumor cells. In seven other samples, a slight blue fluorescence similar to that of AFB was observed, but the toxin was not detected by the chemical assay. In two cases, negative results were registered by both methods. The occurrence of AFB-macromolecules complexes not extractible by organic solvents and differences in the sensitivities of the two methods may explain the observed discrepancies.