bluuebunny/crossref_metadata_2025_split huggingface dataset:
Congenital malformations detected in 731 autopsies of children aged 0 to 14 years
Authors: Mattos Tamara C. , Giugliani Roberto , Haase Hugo B. 
Published: June 2005

AbstractA retrospective study of 731 autopsies of children aged O to 14 years, performed in the Pathological Anatomy Service of the University Hospital of Porto Alegre from 1977 to 1982, was carried out to determine the frequency, type, and seriousness of congenital malformations. The subjects were divided into five age ranges: stillborn (6), 0 to 24 hours (42), 1 to 30 days (50), 1 to 12 months (24), and 1 to 14 years (9). The malformations were classified as single or multiple (presence of two or more independent defects), and their contribution to death was evaluated. Congenital malformations were detected in 131 autopsies (18%). In most cases the defects were single (91), and the most common ones involved the cardiovascular system (37) and the genitourinary system (21). In the patients with multiple malformations (40), the cardiovascular system (24) and the genitourinary system (19) were also most frequently involved. Defects of the osteoarticular system were also frequently encountered in patients with multiple defects (25), although most of them were deformations caused by mechanical factors. Proportionally, congenital malformations were most frequently detected in the 0 to 24 hour range, which also included the highest proportion of multiple defects in relation to single ones (1:1). Congenital malformations were considered responsible for death in 76% of the 131 cases (87% of the multiple defects patients and 60% of the single defect patients). We believe that the data collected in the present study may contribute to a better understanding of the role played by congenital malformations in child mortality.
Relative potency of four ethylene glycol ethers for induction of paw malformations in the CD‐1 mouse
Authors: Hardin Bryan D. , Eisenmann Carol J. 
Published: June 2005

AbstractTime‐mated CD‐1 mice were orally dosed on gestation day 11 (plug = 0) with distilled water (control) or one of four glycol ethers at a dose of 4 mmol/kg: ethylene glycol monomethyl ether (EGME, 304 mg/kg), ethylene glycol dimethyl ether (EGdiME, 361 mg/kg), diethylene glycol dimethyl ether (diEGdiME, 537 mg/kg), triethylene glycol dimethyl ether (triEGdiME, 713 mg/kg). Fetuses were collected on gestation day 18, weighed, and examined for gross external malformations. Fetuses were cleared and stained to examine paws. There were no signs of treatment‐related maternal toxicity, and intrauterine survival was unaffected by glycol ether treatments. Fetal body weights were significantly reduced only in litters treated with EGdiME. There was no treatment‐related pattern of gross external malformations other than paw defects. Only triEGdiME failed to produce a significant incidence of malformations. Paw defects were present in 87.5% of EGME‐treated litters (68.5% of fetuses), 86.7% of EGdiME‐treated litters (33.8% of fetuses), and 77.8% of diEGdiME‐treated litters (39.7% of fetuses). Hindpaw defects predominated over forepaw, and syndactyly was the most common malformation. The incidences of oligodactyly and short digits were also significantly increased. The similarity of malformations produced by these methyl‐substituted glycol ethers is proposed to be attributable to in vivo conversion to a common teratogen, methoxyacetic acid.
TCDD‐Induced hyperplasia of the ureteral epithelium produces hydronephrosis in murine fetuses
Authors: Abbott B. D. , Birnbaum L. S. , Pratt R. M. 
Published: June 2005

AbstractTCDD (2,3,7,8‐tetrachlorodibenzo‐p‐dioxin) has been recognized as a kidney and palate teratogen for many years. The etiology of the kidney abnormality has not been revealed, and there is some confusion about the exact nature of the defect. This study examines C57BL/6N fetal mouse kidneys from day 14 of gestation through day 17. Pregnant females received a single dose of 0 or 12 μg TCDD/kg by gavage on day 10 of pregnancy. Fetal urinary systems were examined on days 14, 15, 16 (A.M.), 16 (P.M.), and 17 (P.M.). The patency of the ureteric lumen was examined by injection of dye into the bladder. TCDD treatment did not delay or prevent breakdown of the ureteric membrane between days 15 and 16. On days 16 through 17, the ureteric lumina of TCDD‐exposed fetuses were narrow and tortuous when compared to the control lumens. Sections of ureter were observed by light microscopy. On day 15 the lumina of TCDD‐exposed ureters were occluded by epithelial cells. As a result of hyperplasia of the ureteric luminal epithelium, hydroureter and hydronephrosis became pronounced by day 17. We conclude that the kidney abnormality induced by TCDD is true hydronephrosis, which is defined as the accumulation of urine in the kidney due to obstructed outflow.
TCDD alters the extracellular matrix and basal lamina of the fetal mouse kidney
Authors: Abbott B. D. , Morgan K. S. , Birnbaum L. S. , Pratt R. M. 
Published: June 2005

AbstractThe teratogenic effects of the dioxin 2,3,7,8‐tetrachlorodi‐benzo‐p‐dioxin (TCDD) have previously been studied in several species, and hydronephrosis has been reported to be a frequent abnormality in near‐term fetuses. C57BL/6N female mice, given 12 μg/kg TCDD, P.O., on day 10 of gestation were killed on days 14, 15, and 16; fetal kidneys were collected and prepared for either immunofluorescent localization of several extracellular matrix components (ECM) or transmission electron microscopy (TEM). The TCDD‐treated and control kidneys showed the same pattern of staining for fibronectin, but TCDD‐treated kidneys displayed a diminished overall intensity. The intensity of laminin and type IV collagen immunofluorescence also appeared to be decreased, and deviations in the pattern of antibody binding were detected for differentiating TCDD‐treated nephrons. Binding of the laminin antibody to the basal lamina was decreased in the parietal layer of Bowman's capsules in more advanced stages of differentiation. TEM analysis focused on the basal lamina of the tubules and Bowman's capsule. In TCDDD‐exposed kidneys, ECM componets adjacent to differentiating nephrons were less abundant, and the basal lamina of the developing Bowman's capsules had a diminished lamina densa. The earliest nephrons to develop display these defects and comprise the first functional filtration units of the metanephric kindney. These ultrastructural changes noted in TCDD‐exposed nephrons may promote proteinuria, a condition normally observed in the developing kidney when the filtration barrier is immature.
A stage‐dependent effect of ethanol on 9.5‐day rat embryos grown in culture and the role played by the concomitant rise in osmolality
Authors: Clode A. M. , Pratten M. K. , Beck F. 
Published: June 2005

AbstractThe effects of ethanol on the rat embryo undergoing organogenesis in vitro have been studied. We have shown that embryopathy is dependent on the stage of development at which explanted embryos were treated. The early neural plate (presomite) stage was highly sensitive to a 4‐hour exposure of 300 mg/% ethanol, whereas embryos explanted 5 hours later, at the late head‐fold (two to six somites) stage grew normally under the same conditions. We have also established that raised serum osmolality, associated with ethanol in serum, is responsible for some but not all of the teratogenic effect. This was shown by mimicking the rise in osmolality with hyperosmotic serum, containing glycerol, NaCl, or concentrated Hanks' salts. Dilution of this osmotic effect by the addition of distilled water in part reversed these embryopathic effects.
Valproic acid
Authors: Lammer Edward J. , Sever Lowell E. , Oakley Godfrey P. 
Published: June 2005

AbstractValproic acid use during pregnancy results in an absolute risk for spina bifida of 1–2%. This increased risk is comparable to the recurrence risk for neural tube defects and warrants informed counselling and access to prenatal diagnosis. There is no substantial evidence that valproic acid use increases the risk for other specific major malformations above the increased risk due to maternal epilepsy. Valproic acid may cause a characteristic pattern of minor facial malformations. Further definition and confirmation are required, and the magnitude of the risk needs to be determined. There are inadequate data to assess the magnitude, if any, of the risks for postnatal growth abnormalities and developmental disabilities associated with the use of valproic acid during pregnancy. Birth‐defect monitoring programs and international collaboration among the staffs of monitoring programs played a major role in determining that valproic acid is a human teratogen.
Amyoplasia congenita‐like condition and maternal malathion exposure
Authors: Lindhout D. , Hageman G. 
Published: June 2005

AbstractThis report concerns an amyoplasia‐like condition in a case with maternal exposure to malathion during the 11th to 12th week of pregnancy. Malathion is an agent acting on the neuromuscular system. The possibility of a causal association is discussed.
Cytotoxic effects of ethylene glycol monomethyl ether in the forelimb bud of the mouse embryo
Authors: Greene J. A. , Sleet R. B. , Morgan K. T. , Welsch F. 
Published: June 2005

AbstractThe role of cytotoxicity in digital maldevelopment in CD‐1 mouse embryos was examined following dosage with ethylene glycol monomethyl ether (EGME) on gestation day (gd) 11. Patterns of cell necrosis in the forelimb buds of embryos collected from dams given EGME orally at doses of 100, 250 or 350 mg/kg were characterized by staining with Nile blue A. Cell death was induced in the mesenchymal tissue and to some extent in the limb bud ectoderm, including the apical ectodermal ridge in a dose‐related manner. The area of preaxial physiological cell necrosis was enlarged by EGME, and the shape of the limb buds was altered 24 hr after treatment. Preaxial tissue and the predigital chondrocyte condensations were reduced or missing following 250 and 350 mg EGME per 1 kg. Light and electron microscope evaluations of forelimb buds revealed the presence of phagocytic vacuoles and condensed, fragmented cytoplasm, which indicate cytotoxicity, as early as 2 hr following EGME, a maximum effect being observed 6 hr after the dose was administered. Although the severity of the cytotoxic response appeared to be dose‐related, comparison with the incidence of digital malformations in near‐term fetuses indicates that the loss of mesenchymal tissue is partially compensated for as formation of the limb progresses.
Developmental toxicity of ethanol in Drosophila melanogaster
Authors: Ranganathan Sulabha , Davis D. Gale , Hood Ronald D. 
Published: June 2005

AbstractEthanol was tested for teratogenicity in Drosophila melanogaster. Treatment consisted of rearing the fly larvae in media containing initial ethanol concentrations of 0%, 4%, 8%, or 14% by weight. Emerging flies were inspected for gross malformations. A low frequency of malformations was seen among controls (0.82%), increasing to 10.36% of emerging adults at the highest ethanol dose. The most common malformation involved the legs (segments missing or distorted or complete absence) and wings (uninflated, distorted, or absent). Less frequent defects included fused or missing mouth parts and missing halteres. Also, by exposing staged larvae to ethanol and examining the emerging flies, developmental stage sensitivity of Drosophila was investigated in terms of timing of treatment initiation. The results suggested that the incidence of defects increased with length of exposure. These results support the assumption that ethanol itself is the causative agent in ethanolinduced developmental toxicity and further support the use of Drosophila for developmental toxicity screening.
Experimental hyperphenylalaninemia in the pregnant guinea pig: Possible phenylalanine teratogenesis and p‐chlorophenylalanine embryotoxicity
Authors: Kronick Jonathan B. , Whelan Donald T. , McCallion David J. 
Published: June 2005

AbstractMaternal hyperphenylalaninemia (HPH) due to deficient phenylalanine (Phe) hydroxylation is a recognized human teratogen associated with an increased incidence of intrauterine growth retardation, microcephaly, congenital heart disease, and mental retardation. There are no previous reports of experimental HPH during organogenesis. Sustained HPH was produced in pregnant guinea pigs by adding 3.5% Phe and 1.0% para‐chlorophenylalanine (pCPA), an inhibitor of Phe hydroxylase, to standard guinea pig chow. Animals consumed the supplemented test diets from gestation day 1 until killed on gestation day 17. Examination of day 17 embryos revealed that embryonic mortality was associated only with maternal pCPA administration and was independent of the degreee of maternal HPH. Embryonic malformation was associated with maternal HPH as well as maternal pCPA administration. Both maternal HPH and pCPA administration were associated with embryonic growth retardation. There was no association between maternal food intake or plasma tyrosine levels and embryonic abnormality or mortality. Both Phe and tyrosine were found to be concentrated in gestation day 17 yolk sac fluid when compared to maternal plasma Phe and tyrosine. The association of embryonic malformation and maternal HPH is consistent with human data. The embryotoxicity of pCPA requires further study and highlights the necessity of appropriate controls in models of experimental HPH.
Atelencephalic microcephaly: Craniofacial anatomy and morphologic comparisons with holoprosencephaly and anencephaly
Authors: Siebert Joseph R. , Kokich Vincent G. , Warkany Josef , Lemire Ronald J. 
Published: June 2005

AbstractThis is the first detailed report of the craniofacial anatomy of atelencephaly. Comparisons were made with a control specimen and others with holoprosencephaly, anencephaly, and anencephaly with holoprosencephalic facial features. In the atelencephalic fetus, severe microcephaly, flattened calvaria, and partial synostosis of the metopic suture were apparent. The cranial fossae were much smaller than usual; lesser wings of the sphenoid were folded into a rounded basal mass. Facial features were pronounced, and orbits were hyperteloric, lowset, and rounded. Ethmoidal cartilages, nasal bones, and maxillary structures were distorted and elongated. The secondary palate was displaced inferiorly and cleft. Because major components of the craniofacial complex were generally present, although misshapen, changes in the atelencephalic skull seem to be deformations rather than malformations. Differences in the cranial morphology of associated disorders–holoprosencephaly and anencephaly–can be construed as aberrations of separate developmental fields. Relationships between atelencephaly and these fields are unclear.
Atypical malformations in an infant exposed to warfarin during the first trimester of pregnancy
Authors: Ruthnum P. , Tolmie J. L. 
Published: June 2005

AbstractWe report a dysmorphic female infant whose mother took warfarin in therapeutic doses during the first 6 weeks of pregnancy. At birth the infant was small for dates and had a triangular facial appearance, micrognathia, microglossia, short fingers and toes, and hypoplastic nails. A skeletal survey revealed hypoplastic distal phalanges in the fingers and toes; there was no epiphyseal stippling. The pattern of malformations present in this infant may either represent the earliest teratogenic effects of warfarin or the fortuitous association of exposure to warfarin and unexplained dysmorphic features.
Structure– toxicity relationships of the tetramethylated tetralin and indane analogs of retinoic acid
Authors: Howard W. Brian , Willhite Calvin C. , Sharma R. P. 
Published: June 2005

AbstractThe teratogenicity of retinoids containing either tetramethylated tetralin (Ro 13‐6307 or Ro 13‐2389) or tetramethylated indane (Ro 13‐4306) ring system substitutions was compared to the teratogenic potency of all‐trans‐retinoic acid. Single oral doses, administered to Syrian Golden hamsters at 10:00 A.M. on day 8 of gestation, induced a syndrome of malformations identical to that induced by treatment with all‐trans‐retinoic acid. These retinoids failed to induce signs of maternal hypervitaminosis A at doses associated with a significant teratogenic response. The tetramethylated tetralin retinoids and indane retinoid were 18 and 2.4 times as embryotoxic on a molar basis, respectively, as all‐trans‐retinoic acid. Introduction of a supplementary ring in the side‐chain restricted polyene chain flexibility and maintained the hydrophobic plane of the chain. The present results are consistent with previous studies showing that the presence of or biotransformation to a free acid congener was necessary for retinoid teratogenic activity in hamsters and that increasing conformational restriction of acidic retinoids increased teratogenic potency.
Acardiac fetus in a triplet pregnancy
Authors: Landy Helain J. , Larsen John W. , Schoen Michael , Larsen Melissa E. , Kent Stephen G. , Weingold Allan B. 
Published: June 2005

AbstractThe acardiac monster represents one of the most severe but rare congenital anomalies. It occurs only in multiple gestations associated with vascular anastomoses between the affected fetus and its co‐twin. The prenatal diagnosis of an acardiac fetus must be suspected in any multiple gestation in which cardiac activity cannot be documented sonographically in a growing fetus. We report an acardiac fetus occurring in a spontaneously conceived triplet pregnancy. A review of the literature, including pathogenetic theories and sonographic reports, is discussed.
Evaluation of a temporal increase in ventricular septal defects: Estimated prevalence and severity in northeastern New York, 1970–1983
Authors: Spooner Eric W. , Hook Ernest B. , Farina Matthew A. , Shaher Reda M. 
Published: June 2005

AbstractA marked increase or “epidemic” in ventricular septal defects (VSD) in recent years has been reported by the Center for Disease Control. Many pediatric cardiologists believe that this increase is simply a reflection of more intensive diagnosis and evaluation of infants throughout the country. Yet to our knowledge there has been no objective evidence for this explanation. We evaluated this possibility by considering records on live births occurring in 1970–1983 in the counties surrounding Albany, New York. In that period a single group of pediatric cardiologists has been evaluating all infants with suspected or confirmed cardiac defects in this area. We limited this analysis to ventricular septal defects unassociated with any cardiac syndrome complex. Thus, VSDs occurring as part of cyanotic heart disease or other complex cardiac “syndromes” were excluded. Consistent with the reported national trend, the estimated prevalence rate of ventricular septal defects diagnosed under 1 year of age in this period has increased from 1.0 per 1,000 live births in 1970 to 4.0 per 1,000 in 1983. Several factors indicate that this rise resulted from more intensive diagnoses at earlier ages in this period: (1) for all patients with VSD, the median age at diagnosis fell from 251 days in 1970 to 25 days in 1983; (2) the most severe VSDs (based on an index derived from pathophysiologic data) were constant from 1972 afterward at an estimated rate of about one per 1,000 (although the estimated rates were lower than this in 1970 and 1971) while the milder defects rose from an estimated rate under 0.5 per 1,000 to over 3.0 per 1,000 in this interval; (3) changes in diagnostic criteria for VSD occurred, so that a murmur thought to be innocent in 1970 might, if heard later in the interval, lead to a diagnosis of VSD; (4) echocardiography began in the latter part of the interval, and the sharpest increase in the estimated rate of VSD occurred after its introduction in 1977 in our area; (5) the prevalence of complex VSD remained relatively stable throughout the period, being 0.4 per 1,000 live births in the first 3 years of the study and 0.5 per 1,000 in the last 3 years; (6) there was an increase in diagnoses of spontaneous closure of VSDs from 7% in 1970 to 32% in 1983. All of these factors are consistent with the view that the increase of VSD resulted from changes in ascertainment due to changes in methods and criteria for diagnosis of this defect.
Strain differences in teratogenic susceptibility to trypan blue between WM and BDIX rat strains
Authors: Hoshino Kiyoshi , Oda Sen‐Ichi , Fukui Yoshihiro , Kameyama Yoshiro 
Published: June 2005

AbstractFemale rats of WM (Wistar‐Mishima)/Nem strain were mated with WM/Nem (group W) or BDIX/Nem males (group WB), and BDIX/Nem females were mated with BDIX/Nem (group B) or WM/Nem males (group BW). On day 8 of gestation, pregnant females were treated intraperitoneally with 1% aqueous solution of trypan blue at a dose of between 20 and 120 mg/kg of body weight. On day 20 of gestation, fetuses were examined for external, visceral, and skeletal malformations.In group W, fetal mortality increased dose dependently at doses higher than 20 mg/kg, and incidences of external, visceral, and skeletal malformations were significantly higher than control at doses of 30 mg/kg and more. In group B, fetal mortality and the incidence of external malformations were significantly higher than control only in the group treated with 120 mg/kg, and no significant increase of visceral and skeletal malformations was shown. It was confirmed that BDIX strain is much more resistant to trypan blue teratogenicity than WM strain.In group BW, nearly the same teratogenic effects were shown as in group W in terms of fetal mortality and incidence of malformations. However, in group WB, teratogenic effects were not so remarkable as in group BW, suggesting patroclinous effects in teratogenic susceptibility to trypan blue. In group BW, sex differences in teratogenic susceptibility were found; male fetuses were more susceptible to trypan blue than females.
Niridazole metabolism by rat embryos in vitro
Authors: Fantel A. G. , Person R. E. , Tracy J. W. , Juchau M. R. 
Published: June 2005

AbstractWe report the results of studies on the reductive activation of the schistosomicidal agent, niridazole (NDZ). Intact rat embryos in vitro reduced this compound, generating a stable metabolite in the presence of 5% O2. By contrast, embryo and yolk sac homogenates or liver microsomes appeared to require anaerobiasis. Malformation incidence–specifically, axial asymmetry–showed a strong correlation with nitroreductase activity rates when the latter were modulated by oxygen tension.Data presented here suggest that when embryos are exposed to NDZ under conditions of low oxygen in vitro, redox cycling ensues with molecular oxygen serving to oxidize early reduction products. This process continues, regenerating the parent compound until oxygen is depleted locally. The basis of this localized depletion is unknown, but inability of the immature supply system to replete oxygen or demand by precociously aerobic tissues may be involved. Once local anaerobiasis is attained, further reduction could generate toxic metabolites capable of covalently binding cellular macromolecules. Localized hypoxia represents another potential mechanism of dysmorphogenesis.