Annual Meeting Scientific Program August 7-10, 2003

Abstract

Gabrielle Weiss and Lily T. Hechtman, Hyperactive Children Grown Up: Empirical Findings and Theoretical Considerations. New York: Guilford Press, 1986, 367 pp., ISBN 0-89862-66 1-7, $32.50 (US)     

Multiphoton microscopy for pre-clinical evaluation of flow-diverter stents for treating aneurysms

BackgroundConventional histological analyses are the gold standard for the study of aneurysms and vascular pathologies in pre-clinical research. Over the past decade, in vivo and ex vivo imaging using multiphoton microscopy have emerged as powerful pre-clinical tools for detailed tissue analyses that can assess morphology, the extracellular matrix (ECM), cell density and vascularisation. Multiphoton microscopy allows for deeper tissue penetration with minor phototoxicity.ObjectiveThe present study aimed to demonstrate the current status of multimodality imaging, including multiphoton microscopy, for detailed analyses of neo-endothelialisation and ECM evolution after flow-diverter stent (FDS) treatment in an experimental rabbit model of aneurysms.MethodsMultiphoton microscopy tools for assessing autofluorescence and second harmonic generation (SHG) signals from biological tissues were used to evaluate the endovascular treatment of intracranial aneurysms in an animal model of aneurysms (pig, rabbit). Results from multiphoton microscopy were compared to those from standard histology, electronic and bright field microscopy.ConclusionsThe present study describes novel evaluation modes based on multiphoton microscopy for visualising tissue morphology (e.g., collagen, elastin, and cells) to qualify and quantify the extent of neo-intimal formation of covered arteries and device integration into the arterial wall using a rabbit model of intracranial aneurysms treated with FDS.     

Development of the PedsQL? sickle cell disease module items: qualitative methods

Purpose  

The objective of this qualitative study was to develop the items and support the content validity of the PedsQL™ Sickle Cell Disease Module for pediatric patients with sickle cell disease (SCD).     

Steroid Hormone Action in Musculoskeletal Cells Involves Membrane Receptor and Nuclear Receptor Mechanisms

Steroid hormones regulate target cells through traditional nuclear mechanisms as well as by membrane mechanisms. 1 &#102 ,25(OH) 2 D 3 and 24R,25(OH) 2 D 3 bind membrane receptors (mVDR) and mediate their effects on the physiological responses of musculoskeletal cells via protein kinase C (PKC). In cultures of costochondral growth plate chondrocytes, 1 &#102 ,25(OH) 2 D 3 binds the 1,25-mVDR in growth zone cells, activating phospholipase C (PLC), leading to diacylglycerol (DAG) production and PKC translocation to the plasma membrane. It also activates PLA 2 , increasing arachidonic acid release and prostaglandin synthesis. 24R,25(OH) 2 D 3 binds its membrane receptor in resting zone chondrocytes, activating phospholipase D (PLD), and increasing DAG and PKC activity, but translocation does not occur. PLA 2 activity is decreased, reducing arachidonic acid and prostaglandin production. 17 &#103 -Estradiol (E 2 ) activates PKC in both cartilage cells, but DAG is not involved. 1 &#102 ,25(OH) 2 D 3 and 24R,25(OH) 2 D 3 also increase PKC in osteoblasts in a cell-specific manner. Antibodies to the 1,25-mVDR block PKC activation. Membrane-mediated events influence gene expression via signaling cascades, including the ERK1/2 MAP kinases. The ability of steroid hormones to initiate events nongenomically is important for regulation of matrix vesicle (MV) function in the extracellular matrix. MVs have mVDRs, but ligand binding inhibits PKC-zeta (PKC &#145 ) via a mechanism that differs from PKC &#102 activation in the plasma membranes. Treatment of MVs from growth zone chondrocyte cultures with 1 &#102 ,25(OH) 2 D 3 releases stromelysin-1 (MMP-3) and increases TGF- &#103 activation. MMP-3 is also involved in proteoglycan degradation, facilitating calcification. 24R,25(OH) 2 D 3 inhibits PKC &#145 in MV from resting zone cell cultures and inhibits MMP-3 release. Chondrocytes and osteoblasts produce 1,25(OH) 2 D 3 , 24,25(OH) 2 D 3 , and E 2 ; thus, locally produced steroids may function as autocrine regulators of matrix events, including matrix vesicle enzyme activity and matrix protein remodelling during longitudinal growth, calcification, and growth factor activation.     

Recent Developments in Health Care Law: Culture and Controversy

This article reviews recent developments in health care law, focusing on controversy at the intersection of health care law and culture. The article addresses: emerging issues in federal regulatory oversight of the rapidly developing market in direct-to-consumer genetic testing, including questions about the role of government oversight and professional mediation of consumer choice; continuing controversies surrounding stem cell research and therapies and the implications of these controversies for healthcare institutions; a controversy in India arising at the intersection of abortion law and the rights of the disabled but implicating a broader set of cross-cultural issues; and the education of U.S. health care providers and lawyers in the theory and practice of cultural competency.     

Recommended Immunological Strategies to Screen for Botulinum Neurotoxin-Containing Samples

Botulinum neurotoxins (BoNTs) cause the life-threatening neurological illness botulism in humans and animals and are divided into seven serotypes (BoNT/A–G), of which serotypes A, B, E, and F cause the disease in humans. BoNTs are classified as “category A” bioterrorism threat agents and are relevant in the context of the Biological Weapons Convention. An international proficiency test (PT) was conducted to evaluate detection, quantification and discrimination capabilities of 23 expert laboratories from the health, food and security areas. Here we describe three immunological strategies that proved to be successful for the detection and quantification of BoNT/A, B, and E considering the restricted sample volume (1 mL) distributed. To analyze the samples qualitatively and quantitatively, the first strategy was based on sensitive immunoenzymatic and immunochromatographic assays for fast qualitative and quantitative analyses. In the second approach, a bead-based suspension array was used for screening followed by conventional ELISA for quantification. In the third approach, an ELISA plate format assay was used for serotype specific immunodetection of BoNT-cleaved substrates, detecting the activity of the light chain, rather than the toxin protein. The results provide guidance for further steps in quality assurance and highlight problems to address in the future.     

A qualitative exploration of mothers' and fathers' experiences of having a child with Klinefelter syndrome and the process of reaching this diagnosis

Klinefelter syndrome (KS) is a common genetic condition that is currently under-diagnosed. The phenotype is broad, with physical, medical and psychosocial features ranging from mild to severe. When a child is diagnosed with KS, the parents may spend months to years searching for a diagnosis. This study used a qualitative methods approach to explore parents'' experiences of having a child with KS and receiving a diagnosis. Fifteen semistructured one-to-one in-depth interviews were conducted to explore their experiences and views. The interviews were then transcribed, coded and thematically analysed. The interviews revealed that parents had diverse experiences related to: the timing of the diagnosis of their child and reasons why their child was investigated for KS; the information that was provided at the time of diagnosis; the supports that were available and the concerns that parents held for the future of their child. The conclusions from this study were that parents'' experiences of having a child with KS and receiving a diagnosis were complex and multifaceted. This experience was shaped by the timing of when the diagnosis was received, who provided the diagnosis, what information was provided from health-care professionals and that which parents may have encountered on the internet. The long-term experiences for parents were also impacted by the level of support they received. These findings have implications for the process by which KS is recognised by the health-care community and supports available for families.