Showing papers by "Hospital for Sick Children published in 1993"

Anthropometric craniofacial pattern profiles in down syndrome

Abstract: A series of 21 anthropometric craniofacial measurements was performed on 199 individuals with Down syndrome (DS), age 6 months to 61 years. These were compared to age and sex-matched normal standards, and Z score pattern profiles were constructed. These profiles confirmed brachycephaly and reduced ear length. With increasing age, maxillary growth was reduced in comparison to mandibular growth. Clinically, this was manifested by a change in facial shape from the characteristic round face of infancy to an oval shape in later life. Stepwise forward discriminant function analysis identified a subset of three variables (ear length, maxillary arc, and upper facial depth) which could accurately classify greater than 99% of the individuals in the combined sample of affected and unaffected individuals. Of the subjects with DS, 96.8% were classified correctly. These findings demonstrate the usefulness of anthropometric craniofacial pattern profiles in defining abnormal facial dimensions in particular syndromes and documenting the changes that occur with age. The technique should facilitate syndrome recognition, identification of carriers, and comparisons between syndromes. © 1993 Wiley-Liss, Inc.

Valproic Acid Impairs Carnitine Uptake in Cultured Human Skin Fibroblasts. An In Vitro Model for the Pathogenesis of Valproic Acid–Associated Carnitine Deficiency

Abstract: The mechanisms of valproate-associated carnitine deficiency are controversial. The urinary excretion of valproylcarnitine is insufficient to account for tissue carnitine depletion. To explore this mechanism, we studied the effects of valproic acid (VPA) on carnitine uptake in cultured human skin fibroblasts by the method of Tein et al. (Pediatr Res 28:247-255, 1990). Fibroblasts were preincubated with varying concentrations (0-2000 microM) of VPA for 1, 3, 5, 7, 10, 14, 21, and 28 d and then incubated with fixed carnitine concentrations of 50 microM (normal physiologic concentration), 20 microM (as seen in secondary carnitine deficiency disorders), or 5 microM (as seen in the plasma membrane carnitine transport defect). There was an exponential dose-dependent decrease in carnitine uptake with increasing VPA concentrations, and the relative inhibitory effect was the same for all three carnitine concentrations. The mean percentages +/- SD (n-1) of residual carnitine uptake for all combined preincubation periods (1-28 d) and combined carnitine concentrations (5, 20, and 50 mumol/L) with increasing concentrations of VPA varied from 83.4 +/- 2.6% (10 microM VPA) to 56.7 +/- 0.1% (500 microM) to 19.8 +/- 1.3% (2000 microM). The degree of inhibition was directly proportional to the time of VPA preincubation and parallel for all three carnitine concentrations; the longer the preincubation period, the lower the toxic dose of VPA (to a minimum of 450 microM), resulting in a 50% suppression of carnitine uptake (TD50).(ABSTRACT TRUNCATED AT 250 WORDS)

Identification and characterization of sporadic and inherited mutations in exon 31 of the neurofibromatosis (NF1) gene.

Abstract: Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders in humans, and presents with a variety of clinical symptoms, which are highly variable in expression. The mutation rate for NF1 is high, with as many as half of all cases resulting from new mutations. Although the NF1 gene has been cloned and its cDNA sequence determined, the specific role of the NF1 gene product in contributing to the NF1 phenotype has not been clarified. The characterization of NF1 mutations is one of the first steps in correlating genotype with clinical symptoms of the disease. In this paper we describe two independent mutations in exon 31 of the NF1 gene identified following polymerase chain reaction (PCR) amplification, heteroduplexing, and single strand conformational polymorphism (SSCP) analysis. One is a novel insertion that segregates with the disease phenotype in that particular family (5852insTT), while the other is a further example of the sporadic, recurrent C→T mutation previously described in the literature (C5842T). The relationship between these mutations and clinical features of NF1 presented by the patients will be discussed.

Maturity of children to consent to medical research: the babysitter test.

Abstract: The age of maturity of children to consent for medical research is under debate, as different authorities regard the capacity of young teenagers as either satisfactory or not to grant consent without parental participation in the process. The present paper contrasts the generally accepted guideline for ethics in paediatric research in Canada with what the same children are allowed and expected to be able to do as babysitters. This comparison reveals deep incongruences in the way the maturity of the same children is appreciated for two different tasks.

Investigation of vascular compression of the trachea: the complementary roles of barium swallow and echocardiography.

Abstract: To determine the preferred investigation of congenital vascular compression of the trachea, preoperative investigation in 40 patients undergoing surgery 1981-91 was analysed. The importance of preoperative identification of detailed arterial anatomy in determining surgical technique was also assessed in 122 consecutive patients undergoing surgery 1952-91. Of the 40 patients (median age 5 months) seen 1981-91, barium swallow before referral suggested the diagnosis of vascular compression in 26 of 27 (96%). Angiography (1/3), bronchoscopy (0/6), and echocardiography (2/6) were generally unhelpful in diagnosing vascular compression before referral. Echocardiography was performed after referral in 18 consecutive patients since 1986 and the correct arterial anatomy was identified in 16 (88%); hyperinflation resulted in inadequate images in the two others. Barium swallow is the investigation of choice to screen for suspected vascular compression of the trachea; echocardiography at the referral centre can define the arterial anatomy in nearly all patients. Further investigation can be reserved for selected cases.

Regulation of Volume-Modulating Ion Transport Systems by Growth Promoters

Abstract: Exposure of quiescent cells to a variety of growth factors and pharmacological mitogens leads to a cascade of biochemical events and ionic changes that occur within minutes and are believed to play crucial roles in the initiation of cell proliferation. The biochemical events induced by growth promoters include increased turnover of inositol phospholipids, protein phosphorylation and increased transcription of several protooncogenes. Modification of monovalent ion (e.g. Na+ and K+) fluxes across the plasma membrane is one of the earliest changes observed in response to growth carriermediated pathways. One of these pathways is the amiloride-sensitive Na+/H+ antiport.

Principles of drug prescribing in infants and children. A practical guide.

Abstract: Paediatric prescribing is much more complicated than prescribing for adults. The specific and general aspects of paediatric patients, the limitations of commercially available dosage formulations, the vagaries of administering medicines, the general inadequacy of clinical pharmacology training, and the dearth of information about drug use in children all add to the difficulties facing the practitioner who treats infants and children.

What Does Bioelectrical Impedance Spectroscopy (BIS) Measure

Abstract: The resistance of the human body to the flow of an alternating current is related to the volume of fluid in the body;l acute changes in fluid status alter body resistance 2,3 Experiments with infusion of saline4 have shown that bioelectrical impedance analysis is sensitive enough to detect minimal alterations in body fluid volume. Impedance methods can measure both total body water and extracellular fluid (ECF) in humans on the basis of the electrical properties of individual tissues.

The effect of gravity on the resting position of the cat's eye

Abstract: We measured rotation (horizontal, vertical and torsional) and translation (horizontal and vertical) of the paralysed cat's eye in response to 45° steps of orientation presented in a pseudorandom order around the roll and pitch axes (with respect to the horizontal canals). During changes of position of the animal in the roll plane, the eyes rotated towards the lowest part of the orbit (left with left ear down; top when the cat was upside down, etc.) by an average of 0.55°. Changing orientation in the pitch plane evoked vertical rotations of ±1.42° (upwards eye movement during forwards head pitch) and torsional rotations of ±1.3°. All these rotations taken together suggest that the centre of mass is in front of, below and temporal to the centre of rotation. The eyes translated temporally (thus separating by 0.72 mm) during forward pitching and there was a small vertical displacement (0.23 mm) when the animal was upside down. These findings are discussed with respect to a possible role of the extraocular proprioception system.

Bone mass and soft tissue compartments in adolescents with anorexia nervosa.

Abstract: Anorexia nervosa is an eating disorder which occurs most frequently in adolescents and young women. It is characterized by fear of obesity and consequent self-starvation in the pursuit of thinness resulting in marked weight loss and amenorrhea1,2. It is associated with many complications, involving almost all the organs of the body. Several reports indicate that some patients have asymptomatic osteopenia and a few of them develop fractures3,4,5,6,7. We investigated bone mass and the relationship between bone mass and soft tissue compartment measurements in adolescent patients with anorexia nervosa.

Interaction of myelin basic protein isoforms with lipid bilayers studied by FTIR spectroscopy

Abstract: The secondary structure of the naturally occurring isoforms of myelin basic protein (MBP1-8) from human myelin was studied by Fourier transform infrared spectroscopy under a variety of experimental conditions. In aqueous solution each isoform was found to be unstructured. In the presence of negatively charged liquid bilayers MBP1-4 were shown to exhibit an amide I band maximum indicative of the adoption of (alpha) -helical secondary structures. A detailed analysis revealed that significant proportions of (beta) -sheet secondary structure were also present. MBP5 and MBP8, which have significantly less cationic charge than MBP1-4, exhibited an amide I maximum identical to that seen in solution, suggesting that no interaction with the bilayer occurred. Analysis of the lipid CH2 and C equals O stretching vibrations also pointed towards significant interaction of MBP1-4 with the bilayer. The changes in intensity and frequency of these bands which typically accompany the phase transition in the pure bilayer were abolished by addition of the proteins. No such effect was seen for MBP5 and 8, the normal lipid phase transition being apparent. The implications of these results in the aetiology of multiple sclerosis is discussed.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Anti-Idiotypic Regulation of the Alloimmune Response in Patients Transfused with Platelet Concentrates

Abstract: Platelet transfusions have increased markedly in recent years with a resulting awareness of problems associated with transfusion therapy. A major problem in patients who receive multiple platelet transfusions has been the development of alloimmunization and a consequent state of clinical refractoriness to random donor platelet transfusions. Patients develop antiplatelet antibodies which shorten the survival of the transfused platelets; anti-HLA antibodies are most common, but platelet-specific antibodies can also occur. The incidence of alloimmunization to HLA in patients with acute leukemia is approximately 30–40% [1–5].