ABSTRACT
OBJECTIVES: To establish the ultrasonographic fetal growth charts of the pons and the vermis/pons ratio on a multioperator basis in low-risk pregnancies and provide a detailed description of the anatomical and ultrasonographic criteria of normal brainstem growth. METHODS: A prospective, multicenter, multioperator, ultrasonographic study was conducted on 913 fetuses aged 21-36 weeks. The anteroposterior diameter of the pons and the greatest vermal height were measured to establish a growth chart, using a mid-sagittal plane with a posterior transfontanellar approach. The LMS semiparametric statistical method was used to construct the growth charts. Three morphological structures were also examined: the pons arch and its echostructure, the bulbo-protuberential sulcus and the primary vermal fissure. RESULTS: The anteroposterior diameter of the pons and the greatest vermal height were measured in 96.7% of cases. The anteroposterior diameter of the pons and vermis increased linearly with gestational age. The vermis/pons ratio was stable during pregnancy. CONCLUSION: We have drawn the growth charts for the pons and vermis during pregnancy and described the normal ultrasound morphology of the brainstem. Knowledge of these morphological and biometric data could facilitate early screening for pontocerebellar hypoplasia.
Subject(s)
Fetus/anatomy & histology , Pons/embryology , Ultrasonography, Prenatal/methods , Cross-Sectional Studies , Female , Gestational Age , Humans , Pons/anatomy & histology , Pons/diagnostic imaging , Pregnancy , Pregnancy Trimester, Third , Prospective Studies , Reference Values , Statistics, NonparametricABSTRACT
The percutaneous pharmacokinetic parameters of 14C-thymoxamine (4-(2-dimethylaminoethoxy)-5-isopropyl-2-methyl phenyl acetate, moxisylyte, Carlytène) were studied on female hairless rats. Animals received 30.3 mg/kg of thymoxamine-base (CAS 54-32-0) percutaneously (dorsal skin). The decrease of the radiolabelled compound on the skin surface (drug penetration) and the appearance of the total radioactivity in plasma (drug absorption) were measured. The time-course study of the total radioactivity measured on the skin surface indicates a biphasic profile with a rapid decrease during the first h (t1/2 from 0 to 4 h = 1.4 h) and then a less rapid one (t1/2 after 4 h approximately 29 h). Plasma data demonstrated that 14C-thymoxamine was rapidly and almost entirely absorbed (91%) after percutaneous application. The values of absorption parameters suggest that thymoxamine is a compound with a high absorption process using this route of administration. The t(max) value was about 2 h and the half-life of absorption was 0.70 h. Compared to the apparent half-life of elimination observed after oral or i.v. administration (t1/2 = 9 h),the elimination phase of thymoxamine was relatively rapid after percutaneous administration (t1/2 = 15 h). The penetration /absorption phenomenon of thymoxamine base mainly located in the horny layer could explain the higher value of the half-life of elimination observed after percutaneous administration.
Subject(s)
Adrenergic alpha-Antagonists/pharmacokinetics , Moxisylyte/pharmacokinetics , Administration, Cutaneous , Administration, Oral , Adrenergic alpha-Antagonists/administration & dosage , Animals , Female , Half-Life , Injections, Intravenous , Moxisylyte/administration & dosage , Rats , Rats, Nude , Skin AbsorptionABSTRACT
The pharmacokinetics of 14C-thymoxamine (4-(2-dimethylaminoethoxy)-5- isopropyl-2-methyl phenyl acetate hydrochloride) (moxisylyte, Carlytène) was studied on female hairless rats. Animals received 5 mg/kg of thymoxamine-HCl (CAS 964-52-3) intravenously or orally. 14C-thymoxamine was both rapidly and entirely absorbed after oral administration, Tmax value was observed at 0.25 h. The decrease of the total radioactivity followed a biexponential mode. After intravenous and oral administration, the apparent half-live of distribution were 0.20 and 0.31 h, respectively, whereas the apparent half-live of elimination were 9.6 (i.v.) and 8 h (p.o.). The nature and proportions of thymoxamine metabolites recovered in the plasma varied according to the route of administration. After intravenous administration, desacetyl-thymoxamine (DAT) + desacetyl-desmethyl-thymoxamine (DMAT), sulphate conjugates and glucuronides of DAT + DMAT represented 12, 21 and 63%, respectively. After oral administration, the values were 0, 21 and 79%, respectively. These results underlined the importance of the hepatic first-past effect which induced the disappearance of DAT and DMAT, and increased the levels of glucuronides when thymoxamine was orally administered. The level of sulphate conjugates for DAT and DMAT seems always constant.
