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OBJECTIVE: To determine if use of ecstacy during pregnancy has any harmful effects on pregnancy and the (unborn) child. DESIGN: Prospective, descriptive. METHODS: After the Teratology Information Service of the National Institute of Public Health and the Environment. Bilthoven, the Netherlands, was approached by a physician or midwife for information, the pregnancies that involved the use of ecstacy were followed by a follow-up questionnaire one month after the estimated date of birth. RESULTS: A total of 49 pregnancies were followed. For 43 women, exposed early in pregnancy, data on course of pregnancy and health of baby are known. There were 3 elective terminations of pregnancy and 2 spontaneous abortions. There were 40 live-born babies (including one set of triplets); one of them had a congenital cardiac malformation. Beside ecstacy the mothers frequently also used other substances potentially harmful to pregnancy and child. The pregnancies were often unplanned; previous pregnancies had frequently been terminated. CONCLUSION: The sample size was too small to draw conclusions. As yet spontaneous abortions and congenital malformations did not appear to occur more frequently in pregnancies with use of ecstacy. The lifestyle of the ecstacy users seemed to be potentially harmful for pregnancy and child.

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In the few past years the Netherlands Centre for Monitoring of Adverse Reactions to Drugs and the Teratology Information Service of the National Institute of Public Health and Environmental Protection received several reports of neurological symptoms in neonates, which were the result of maternal treatment with psychotropic drugs during late pregnancy. The results are summarised in this article. The neonatal symptoms (withdrawal symptoms, 'floppy infant syndrome' and extrapyramidal syndrome) are described together with the psychotropic drugs which may cause them.

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After an intramuscular injection of nalbuphine during parturition a foetal bradycardia of 30-40 beats/minute developed, which normalised after an intravenous maternal injection of naloxone. Because the cardiotocography did not show variability after the event, a caesarean section was performed. Six months later the child still had a severe neurological disorder which was attributed to intrauterine asphyxia. Several authors published reports in which no relevant clinical problems were described after nalbuphine given during labour. Recently, however, four children have been described with bradycardia and respiratory depression after maternal intravenous and/or intramuscular injection of nalbuphine. Apparently, the use of nalbuphine during labour can cause foetal bradycardia, both after intravenous and after intramuscular administration. Great reserve is advised regarding use of nalbuphine for this indication. The antidote naloxone should be within reach.

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The post-implantation rat embryo culture technique is employed to study embryotoxic effects of xenobiotic compounds in the absence of the maternal compartment. For compounds biotransformed in vivo the embryo culture technique must be adapted in order to mimick the in vivo effects. In the present study the possibility of co-culturing metabolically active maternal hepatocytes suspended in the standard culture system with rat serum as a medium was investigated. Cyclophosphamide (CP) was used as a model compound as it needs bioactivation to display embryotoxicity. Morphologic and histologic effects were studied. Neither hepatocytes nor CP alone affected embryo development, whereas in the presence of hepatocytes embryotoxicity was observed at 30 micrograms/ml CP. Embryotoxicity was decreased in the additional presence of metyrapone, a monoxygenase inhibitor. Hepatocyte suspensions prepared via slicing or perfusion of livers were equally effective. In conclusion, co-culture of embryos and suspended hepatocytes can be performed under optimal conditions for embryo development and in the presence of biotransforming activity.

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When rat embryos are grown in culture, the morphological scoring system of Brown & Fabro (Teratology 1981, 24, 65-78) is usually employed at the end of culture to assess normal development and the effects of drugs and other chemicals. The morphological scoring system has proved very satisfactory, but its criteria only involves the external appearance of the embryo. It seems desirable to study also the internal anatomy of the embryo by histological methods. Thus, the object of this study was to gain data on the morphology of the main organ systems, with special attention given to the cardiovascular system during the developmental period most often employed in teratogenicity and embryotoxicity studies (day 9-10; 18-22-somites stage). The microscopic findings in this study agreed well with the morphological scoring system, with only one exception; whereas only two branchial arches were visible externally at the 18-22-somites stage, microscopy revealed that the third arch was also present.

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The histological methods used in checking the administration of oestrogens to fattening calves, introduced in the Netherlands in 1967, are discussed. Because of the increased use of combined treatment with oestrogens and androgens (both synthetic and natural), the suitability of the above histological techniques has become doubtful. Moreover, exogenous natural steroid hormones were not found to constitute any hazard to public health and could be safely used in husbandry. If administration of such anabolics is permitted the reasons for histological examination would cease to exist.

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This study is concerned with the histopathological changes and tumors and their incidences in the Wistar SPF Tox rat. Also included are data on survival, growth and haematology. The animals were untreated and were investigated for 30 months. The data are compared with those from two Wistar substocks, which had been used in the same laboratory: the Wistar CPB and the Wistar Conv. The results are summarized in tables and figures and are compared with data from the literature. A survey of studies dealing with spontaneous lesions and tumors in rats is given. A wide variety of tumor types and a relatively high tumor incidence were found in the Wistar SPF Tox rats. Since most of the tumors were found after 24 months, this high incidence was correlated with the life expectancy.

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The carcinogenicity of maleic hydrazide is discussed by several national and international organizations because of contradictory results of a number of carcinogenicity studies carried out in the past. Because maleic hydrazide is used in agriculture on edible crops, an oral carcinogenicity study with rats was carried out for 28 months at dietary levels of 0, 1.0 and 2.0% maleic hydrazide which contained less than 1.5 mg hydrazine/kg product as impurity. In this study as well as in an experiment with mice carried out with the same batch of maleic hydrazide at the International Agency for Research on Cancer (IARC) in Lyon, France, treatment did not affect tumor incidence and it was concluded that maleic hydrazide itself is not a carcinogen. Most likely the presence of relatively high levels of hydrazine as an impurity was responsible for the contradictory results in studies as reported previously. Furthermore the results of this study showed that 1.0 and 2.0% maleic hydrazide in the diet caused proteinuria and increased protein/creatinine ratio's in the urine in both sexes without detectable histopathological changes in kidney or urinary tract. From this study, based on the effects of kidney function the "no-toxic" effect level is considered to be lower than 1.0% maleic hydrazide in the diet of rats.

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