Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019270 (hernia)
 15,856 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The contribution of an abnormal pulmonary vascular bed to right-to-left shunting in patients with congenital left-sided diaphragmatic hernia and alveolar hypoplasia has not been defined. In three infants we analyzed lungs fixed by perfusion. Left lung volumes (ml/kg birth weight) were 1.7, 6.5 and 4.0 respectively (control = 11.7) and right lung volumes 5.7, 11.7 and 9.8 respectively (control = 14.3). Serial sections were prepared and fifth generation (resistance) vessels identified. Compared to control the medial widths were increased in all lungs and the medial width/external diameter ratios were increased in the left lungs of two patients and the right lung of one. The m/d ratio in the left lung was greater than that in the right lung in two of the three patients. There were fewer pulmonary vessels/cm2 lung tissue in the study lungs than in the control lung, and there were significantly fewer pulmonary vessels/cm2 lung tissue in the left than in the right lung in two of the three patients. Although there was increased smooth muscle in resistance vessels, intravenous therapy with tolazoline HCl did not improve systemic oxygenation. We conclude that this was probably due to the decreased total size of the pulmonary vascular bed and the decreased number of pulmonary vessels per unit lung tissue, causing a fixed high pulmonary vascular resistance.
 ...
PMID:Morphologic analysis of the pulmonary vascular bed in congenital left-sided diaphragmatic hernia. 64 33

Bendectin, composed of doxylamine succinate and pyridoxine HCl (1:1), is an antinauseant previously prescribed for nausea and vomiting during pregnancy. The present study examined the maternal and developmental effects of Bendectin (0, 200, 500, or 800 mg/kg/day, po) administered to timed-pregnant CD rats (36-41/group) during organogenesis (gestational days [gd] 6-15). At death (gd 20), all live fetuses were examined for external, visceral, and skeletal abnormalities. At 500 and 800 mg/kg/day, maternal toxicity included reduced food consumption during treatment and for the gestation period, increased water consumption in the posttreatment period, reduced weight gain during treatment, and sedation; water consumption was reduced during treatment and for the gestation period, and maternal mortality (17.1%) was observed only at the high dose. Developmental toxicity included reduced prenatal viability (800 mg/kg/day) and reduced fetal body weight/litter (500 and 800 mg/kg/day). In addition, reduced ossification of metacarpals (800 mg/kg/day), phalanges of the forelimbs (500 and 800 mg/kg/day), and of caudal vertebral centra (all doses) was observed. No increase in percent malformed live fetuses/litter was observed. The proportion of litters with one or more malformed fetuses was higher than vehicle controls only at 800 mg/kg/day, with short 13th rib (to which the test species is predisposed) as the predominant observation. By contrast, a positive control agent (nitrofen, 50 mg/kg/day, po, 14 dams) produced 85% malformed fetuses/litter with the predominant malformation being diaphragmatic hernia. In conclusion, the incidence of litters with one or more malformed fetuses was increased only at a dose of Bendectin which produced maternal mortality (17.1%) and other indices of maternal and developmental toxicity (see Discussion).
 ...
PMID:Developmental toxicity evaluation of Bendectin in CD rats. 340 69

Pregnant Wistar rats were administered 0, 100, 400 or 1000 mg mono-n-butylamine hydrochloride/kg body weight/day by gavage on days 6 through 15 post coitum (sperm-positive=day 0), or inhaled mono-n-butylamine 0, 17, 50 or 152 ppm (whole-body exposure), 6 h/day on days 6 through 19 post coitum. Oral n-butylamine HCl 1000 mg/kg reduced maternal feed consumption, increased early post-implantation losses (embryonic resorptions), reduced fetal and placental weight, and retarded skeletal development (incomplete skull and sternebral ossification), and produced malformations (filiform/kinked tail, enlarged cardiac ventricular chamber(s), malpositioned heart, aortic arch atresia, diaphragmatic hernia); 100 mg/kg was the no-observed-adverse effect level (NOAEL) for prenatal developmental toxicity; 400 mg/kg, the maternal no-effect level, produced only malformations (aortic arch atresia, malpositioned heart, diaphragmatic hernia). Inhaled n-butylamine produced concentration-dependent nasal epithelial hyperplasia and squamous metaplasia, inflammation and necrosis; the maternal NOAEL was less than 17 ppm. There were no treatment-related signs of embryo/fetotoxicity, particularly, no effects on fetal morphology. The developmental NOAEL was 152 ppm. The neutralization of n-butylamine by hydrochloride converts it from a strong alkali causing tissue burns into a weak acid/base which is fetotoxic. Possible mechanisms of fetotoxicity are free radical production, metabolic acidosis, and lysosomotrophy.
 ...
PMID:Developmental toxicity of oral n-butylamine hydrochloride and inhaled n-butylamine in rats. 1241 98