ISSN:0040-3709    

DOI:10.1002/tera.1420460503

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

ISSN:0040-3709    

DOI:10.1002/tera.1420460504

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

ISSN:0040-3709    

DOI:10.1002/tera.1420460505

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThis paper introduces and discusses the use of standardized residuals as a technique for comparing the growth of normal and pathologic human fetuses. Anthropometric measures, radiographic measures, and organ weights were regressed on known gestational age of second‐ and third‐trimester fetuses. Standardized residuals were calculated for a group of potentially growth‐impaired fetuses. Use of residuals aids in identification of patterns of growth alteration in specific pathologies. Most important, studying the response of developing organ systems to a variety of insults may elucidate mechanisms of growth regulation in the fetus. We emphasize the special quality of the multivariate measures of the core sample of fetuses from the Akron Children's Hospital collection. © 1992 Wiley‐L

ISSN:0040-3709    

DOI:10.1002/tera.1420460506

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractNorfloxacin, an orally active fluoroquinolone antimicrobial, has been reported to be embryolethal but not teratogenic when administered to pregnant cynomolgus macaques prior to gestational day (GD) 36 at doses ≤200 mg/kg/day. Additional studies have been performed in an effort to examine the mechanism responsible for this effect, particularly regarding the role of progesterone (P). The first study (Study I) investigated the effect of norfloxacin administration during early pregnancy (200 mg/kg/day; daily GD 20–30) in the absence of a functional corpus luteum (CL). The CL was surgically removed from 16 gravid females on GD 19 in order to focus on placental‐derived P; ten were dosed with norfloxacin and six received vehicle only. Embryolethality was observed for 7/10 (70%) of the treated animals during GD 25–31 versus 0/6 (0%) for controls. A reduction in serum P was noted prior to embryonic loss, although no significant effects on chorionic gonadotropin (CG), 17β‐estradiol (E2), or P or E urinary metabolites were observed. A second study (Study II) was performed in order to evaluate the capacity of norfloxacin (200 mg/kg) to reduce CL‐derived P in both normally cycling and CG‐stimulated nonpregnant females (ten treated, ten controls; daily for 8 days). No effects on P production or on luteal phase or menstrual cycle lengths were observed. The third study (Study III) was designed to examine the effect of norfloxacin on the metabolism and excretion of P in nonpregnant females. Silastic P implants were placed subcutaneously in order to maintain constant P levels during a 10 day treatment regimen (200 mg/kg/day; ten controls, nine treated). Five of the controls and four of the norfloxacin‐treated females also received14C‐P intravenously within 1 hr of the last dose of norfloxacin in order to study excretory patterns. No significant differences between control and treated groups were observed. The results of these studies combined suggest that the developmental toxic effects observed in prior studies and Study I are specific to pregnancy and directly related to placental‐derived P production. ©

ISSN:0040-3709    

DOI:10.1002/tera.1420460507

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe embryotoxic effects of ethylene dibromide (EDB) bioactivation, mediated by purified rat liver glutathioneS‐transferases (GST), were investigated using rat embryos in culture. Significant EDB metabolism was observed with rat liver GST purified by affinity chromatography (specific activity of 188 ± 11.3 nmol/min/mg protein). The reaction was enzymatic in nature and the conjugation rate was proportional to the concentration of EDB (up to 0.75 mM) and the enzyme present in the reaction medium. EDB activation by 100 units (1 unit = 1 nmol of glutathione consumed per min) of purified rat liver GST caused a significant reduction in general development as measured by crown–rump length, yolk sac diameter, somite number, and the composite score for different morphological parameters (Brown and Fabro methodology). Structures most significantly affected were the central nervous and olfactory systems as well as the yolk sac circulation and allantois. The results of this study clearly indicate that under in vitro conditions, bioactivation of EDB by GST can lead to embryotoxicity. © 1992 Wiley‐Li

ISSN:0040-3709    

DOI:10.1002/tera.1420460508

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractTo test the effect of maternal habits and home exposures during early pregnancy on the occurrence of congenital heart disease in the offspring, 406 cases and 756 controls were studied. The cases included all cardiovascular malformations detected in Finland during 1982–1983, while the healthy controls were randomly selected from all babies born during the same period. Case and control mothers were interviewed after delivery using a structured and pre‐tested questionnaire.Maternal overall drug consumption during the first trimester was as prevalent among case mothers (13.3%) as controls (14.6%). Neither was the risk of congenital heart disease associated with maternal use of contraceptive pills, salicylates, diazepam, or sweetening agents separately. Maternal exposures to disinfectants, dyes, lacquers, paints, pesticides, or glues at home were equally prevalent in case and control groups.Several earlier miscarriages was a predictor of an infant born with congenital heart disease (OR = 2.7, CI95= 1.4–5.3). Maternal ultrasound examination was performed during the first 16 weeks of pregnancy more often among the case group (28.3%) than among the control group (22.0%). However, the association between ultrasound examination and the risk of congenital heart disease in the offspring was not statistically significant (OR = 1.2, 95% confidence interval 0.9–1.7) when adjusted for confounding factors such as the threat of miscarriage in logistic regression analysis.It is concluded that maternal ultrasound examination, intake of some common drugs, and exposure to a number of environmental factors at home during early pregnancy are probably not harmful for the developing fetal heart. © 1992 Wiley

ISSN:0040-3709    

DOI:10.1002/tera.1420460509

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe study is based on almost 10 million births and reports on 215 infants with two unusual malformations: amelia and gross body wall defect. Amelia without body wall defect was present in 116 cases, 67 had body wall defects without amelia, and 32 had both. The total rate was 2.2 per 100,000 births. The infants were divided into five mutually exclusive groups. There were 40 infants (0.4 per 100,000) with agenesis of the body stalk, 18 with amelia and other types of gross body wall defects (0.2 per 100,000), 56 with amelia and malformations other than gross body wall defects (0.6 per 100,000), 41 with amelia (with or without other limb reduction defects) but no nonlimb malformations (0.4 per 100,000), and 60 infants with gross body wall defects of a type other than agenesis of body stalk and without amelia (0.6 per 100,000). A weak trend of decreasing prevalence of these malformations was found during the observation period. Infants with agenesis of the body stalk and infants with amelia combined with other types of gross body wall defects occurred at an increased rate in infants of young women. This maternal age effect is also found with gastroschisis, but not with omphalocele, and may indicate etiological or pathogenetic similarities between gastroschisis and the two former groups of defect. In infants with amelia, additional limb reduction defects could be of any type: transverse, longitudinal, or intercalary. Therefore, amelia may be the end result of different types of disturbances of limb morphogenesis. There was an increased rate of twinning. The relationship with amniotic band syndrome is discussed. © 1992 Wiley‐Liss, I

ISSN:0040-3709    

DOI:10.1002/tera.1420460510

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractPaternal alcohol use has been associated with a number of adverse reproductive outcomes in laboratory animals and there is one epidemiologic report of a detrimental effect on infant birth weight. To expand the epidemiologic evidence, data from the Child Health and Development Studies were analyzed. Data collected from the onset of prenatal care in 10,232 women enrolled in the Kaiser Foundation Health Plan and residing in the San Francisco East Bay area between June 1959 and September 1966 were available, including information on the mother's report of paternal alcohol consumption and a number of potential confounders. Pregnancy outcomes included preterm delivery (<37 weeks completed gestation), moderately low birth weight (1,501–2,500 g), very low birth weight (≤1,500 g), small‐for‐gestational‐age (<10th percentile of weight for gestational age), and mean birth weight. Paternal alcohol use, analyzed in intervals from 0 to 2.0 or more drinks per day, showed no association with any of the outcomes of interest. Adjusted prevalence odds ratios ranged from 0.7 to 1.5, with no indication of a monotonic dose‐response gradient. Mean birth weight was also virtually unrelated to paternal alcohol use. Compared with the earlier report, this population had a very modest level of alcohol consumption. Nonetheless, within the range that was studied there appears to be no association between paternal alcohol use and birth outcome. © 1992 Wil

ISSN:0040-3709    

DOI:10.1002/tera.1420460511

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractIn vitro culture of rodent embryos has been extensively used in the search for teratologic agents, with possible relevance to diabetic pregnancy. However, the high concentrations of rat serum added to the culture medium (∼75%) have raised concern that the teratogenic effects of some compounds may be attenuated or masked in this culture system and thereby forced the addition of pharmacological concentrations of the compounds (e.g.,D‐glucose and β‐hydroxybutyrate) to the medium. This issue has been examined in the present study where the effects of different concentrations of rat serum on growth and differentiation of rat embryos were recorded in cultures supplemented with increased concentrations ofD‐glucose and β‐hydroxybutyrate. The embryonic development was also evaluated after culture in medium supplied with serum from diabetic rats. Compared with normal rat serum, the diabetic serum had an elevated glucose concentration as well as markedly increased levels of triglycerides and branched amino acids, indicating a potentially rich supply of major nutrients for the cultured embryos.Lowering the serum concentration in the culture medium from 80% to 50% yielded progressively retarded embryonic growth but no increased rate of other morphological malformations. At 40% serum concentration, however, there was a sharp rise in the incidence of somatic malformations, in addition to the prevailing growth retardation. When the embryonic growth and development were compared at 50% and 80% serum concentrations, increasedD‐glucose or β‐hydroxybutyrate concentrations caused similar degrees of embryonic dysmorphogenesis. Also, the uptake of each compound by the embryos exposed to elevated levels of the two agents were similar in 50% and 80% serum cultures. There was, therefore, no protection against the teratogenic and growth‐retarding effects of increasedD‐glucose or β‐hydroxybutyrate offered by high serum concentrations in the culture medium (i.e., 80% vs. 50%).Embryos cultured in 50% or 80% diabetic rat serum at 30 mmol/L or 50 mmol/LD‐glucose concentration showed similar rates of somatic malformations as did embryos exposed to the same proportion of normal rat serum at similar glucose concentrations. By contrast, the diabetic rat serum amplified the general retarding effects of highD‐glucose levels, yielding lower protein levels and somite numbers in embryos from diabetic serum culture than in embryos cultured in normal rat serum. This effect was achieved despite slightly lower uptake of glucose in embryos cultured in diabetic serum compared to embryos cultured in normal serum (at high glucose and similar serum concentrations). The embryos exposed to elevated levels of β‐hydroxybutyrate in diabetic serum, however, showed slightly enhanced uptake of the ketone body. These findings suggest that diabetic serum alters the embryonic transport of the teratogenic compoundsD‐glucose and β‐hydroxybutyrate. The present study implicates that embryonic development in a diabetic environment can be further studied with the present experimental design, perhaps with the addition of new methods for evaluation of

ISSN:0040-3709    

DOI:10.1002/tera.1420460512

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY