Fragile X syndrome: recognition in young children

In recent years, a number of articles have appeared in the literature concerning the fragile X syndrome; however, in few cases was the diagnosis of the syndrome in young children discussed. A review of 20 children younger than 7 1/2 years of age who had the fragile X syndrome seen at the Cincinnati Center of Developmental Disorders was undertaken in an attempt to establish guidelines that would aid the practicing physician in determining which children should have a chromosomal analysis. All children were developmentally delayed; 95% had speech delays. Short attention span with hyperactivity, temper tantrums, mouthing of objects persisting at an age beyond when it would be expected, autistic behaviors, and poor gross motor coordination were seen in 50% or more of the children. Mental retardation was present in the family history of 65%, and 90% had a family history of at least one of the following: mental retardation, learning disabilities, or hyperactivity. The most common physical findings were long and/or wide and/or protruding ears, prominent jaw and/or long face, high arched palate, and a flattened nasal bridge. The fragile X syndrome can be recognized by noting key aspects of the behavioral and family histories as well as the physical findings.     

What differences are detected by superiority trials or ruled out by noninferiority trials? A cross-sectional study on a random sample of two-hundred two-arms parallel group randomized clinical trials

Background  

The smallest difference to be detected in superiority trials or the largest difference to be ruled out in noninferiority trials is a key determinant of sample size, but little guidance exists to help researchers in their choice. The objectives were to examine the distribution of differences that researchers aim to detect in clinical trials and to verify that those differences are smaller in noninferiority compared to superiority trials.     

Do alpha 2-adrenoceptors and imidazoline binding sites coexist in the human term placenta? Evidence from direct binding studies

Alpha2-Adrenergic receptors and non-adrenergic imidazoline binding sites (IBS) in human placental membranes were investigated by means of the radioligands [3H]-RX 821002 and [3H]-RX 781094 (idazoxan) respectively. Human term placentae (38-40 weeks) were obtained immediately after vaginal delivery. The specific binding of the alpha2- subtype-selective [3H]-RX 821002 confirms the presence of alpha2- adrenoceptors in the human placenta, while [3H]-idazoxan binds to non- adrenergic IBS. The sites were characterized by displacement analyses with various imidazoline and non-imidazoline drugs. The presence of an endogenous ligand for IBS has not yet been demonstrated. Clonidine displacing substance (CDS) was recently identified as agmatine; it recognizes both alpha2 and imidazoline receptors. This phenomenon was studied in crude placental membranes. The studies revealed that: (i) alpha2-adrenoceptors coexist with non-adrenergic IBS in human placental membranes; (ii) there is a strong probability that alpha2-adrenoceptors and IBS are pharmacologically distinct; and (iii) agmatine binds to placental alpha2 and imidazoline receptors with different affinities.      

Twin reversed arterial perfusion sequence in twin-to-twin transfusion syndrome after the death of the donor co-twin in the second trimester.

A twin-to-twin transfusion syndrome was diagnosed in a monochorionic-diamniotic pregnancy at 18 weeks' gestation without any malformation, especially heart defect. In spite of the aggressive treatment (serial amnioreduction, digoxin treatment) the donor twin died at 25 weeks and twin reversed arterial perfusion (TRAP) sequence developed and was documented by Doppler ultrasound. In the TRAP-twin, the route of the reversed blood flow from the umbilical arteries was as follows: descending aorta, aortic arch, ascending aorta, aortic valve, left ventricle, mitral valve, left atrium, foramen ovale, right atrium, inferior vena cava, ductus venosus; and back to the placenta through the umbilical vein. After a 12-h observation period the twin reversed arterial perfusion sequence disappeared. During this period ultrasound and fetal blood sampling revealed no sign of fetal anemia or disseminated intravascular coagulation in the surviving twin. Based on our observations, we propose, that the death of one of the twins in monochorionic pregnancy can result in twin reversed arterial perfusion sequence, which is an ultimately rare phenomenon in the second trimester. To our knowledge, this is the first reported case of twin reversed arterial perfusion sequence subsequent to the intrauterine demise of one twin in twin-to-twin transfusion syndrome in which the TRAP-twin had no cardiac malformation.     

Are platelets activated after a rapid, one-step density gradient centrifugation? Evidence from flow cytometric analysis

This procedure describes the preparation of platelets from whole blood of healthy donors and pregnancy-induced hypertensive (PIH) patients by a rapid, one-step density gradient centrifugation, and the direct immunofluorescence staining of obtained platelets (CD63). Platelets are relatively fragile structures. Consequently, for the investigation of their biochemical properties it is recommended to isolate them by a simple method that does not damage their functional parameters and induce their activation. During platelet activation, several changes occur at the platelet surface. CD63 is the receptor for a lysosomal glycoprotein expressed in activated platelets. Currently, flow cytometry (fluorescence-activated cell sorting) is the most sensitive method to detect increased surface exposure of activation antigens on the platelet surface. The present technical note describes that compared with other whole blood flow cytometric techniques, our one-step density-gradient centrifugation method using OptiPrep can also prevent artificial, sample manipulation-related platelet activation.     

Imidazoline receptors in the human umbilical cord

Imidazoline binding sites (IBS) are now accepted as being receptors, however, their physiological functions are not yet clearly understood. Previously, the authors demonstrated that the density of IBS in the human placenta significantly increased throughout gestation. The present study was performed for the identification of imidazoline receptors in the human umbilical cord.