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Bakri Elsheikh MBBS MRCP Thomas Prior PhD Xiaoli Zhang PhD Robert Miller MD Stephen J. Kolb MD PhD Dan Moore PhD Walter Bradley DM FRCP Richard Barohn MD Wilson Bryan MD Deborah Gelinas MD Susan Iannaccone MD Robert Leshner MD Jerry R. Mendell MD Michelle Mendoza PT Barry Russman MD Stephen Smith MD Wendy King PT John T. Kissel MD 《Muscle & nerve》2009,40(4):652-656
To evaluate the effect of SMN2 copy number on disease severity in spinal muscular atrophy (SMA), we stratified 45 adult SMA patients based on SMN2 copy number (3 vs. 4 copies). Patients with 3 copies had an earlier age of onset and lower spinal muscular atrophy functional rating scale (SMAFRS) scores and were more likely to be non‐ambulatory. There was, however, no difference between the groups in quantitative muscle strength or pulmonary function testing. Functional scale may be a more discriminating outcome measure for SMA clinical trials. Muscle Nerve, 2009 相似文献
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Alistair Q. Green MBBS Singhan T. Krishnan MBBS MD Gerry Rayman MBBS MD 《Muscle & nerve》2009,40(6):985-991
Vasodilation induced by both acetylcholine iontophoresis (ACh Ionto) and the laser Doppler flare technique (LDIFT) can be used to measure small‐fiber function. The aim of this study was to compare the neurogenic nature of these methods. ACh Ionto and the LDIFT were performed on 10 controls, with and without local anesthetic cream. The local anesthetic cream blocks the axon reflex; thus, by determining the ratio of hyperemic area to stimulus area before and after anesthesia, the neurogenic nature of the hyperemia can be determined. The ratio of hyperemic area to stimulus area was significantly reduced by local anesthesia in the LDIFT [ratio (mean ± SD): 2.33 ± 0.67 with local anesthesia; 6.84 ± 1.33 without local anesthesia; P < 0.0001], whereas this ratio was unaffected by local anesthesia in the ACh Ionto group (2.61 ± 0.57 with local anesthesia; 2.67 ± 1.27 without local anesthesia). This study confirms that the LDIFT measures small‐fiber function. In contrast, hyperemia elicited by ACh Ionto outside the capsule is not blocked by local anesthesia and is thus non‐neurogenic. Muscle Nerve, 2009 相似文献
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Sharavanan Parasivam MBBS FRACP Max Cowey BSc Bruce Day MBBS FRACP Dominic Thyagarajan MBBS MD FRACP 《Movement disorders》2009,24(3):422-425
Multimodal representation of peripersonal or near space has been demonstrated in the brain of the nonhuman primate through invasive electrophysiological experiments. Representation of peripersonal space in the human brain has been inferred from extinction experiments and functional imaging studies. We present a unique case of lower limb myoclonus in a patient with common variable immunodeficiency which is sensitive to visual stimuli in the peripersonal space and light touch. This case provides further evidence for near space representation in the human brain. We hypothesize that somatopically organized multimodal areas exist in the human brain which code for peripersonal space. © 2008 Movement Disorder Society 相似文献
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Leslie G. Biesecker James C. Mullikin Flavia M. Facio Clesson Turner Praveen F. Cherukuri Robert W. Blakesley Gerard G. Bouffard Peter S. Chines Pedro Cruz Nancy F. Hansen Jamie K. Teer Baishali Maskeri Alice C. Young NISC Comparative Sequencing Program Teri A. Manolio Alexander F. Wilson Toren Finkel Paul Hwang Andrew Arai Alan T. Remaley Vandana Sachdev Robert Shamburek Richard O. Cannon Eric D. Green 《Genome research》2009,19(9):1665-1674
ClinSeq is a pilot project to investigate the use of whole-genome sequencing as a tool for clinical research. By piloting the acquisition of large amounts of DNA sequence data from individual human subjects, we are fostering the development of hypothesis-generating approaches for performing research in genomic medicine, including the exploration of issues related to the genetic architecture of disease, implementation of genomic technology, informed consent, disclosure of genetic information, and archiving, analyzing, and displaying sequence data. In the initial phase of ClinSeq, we are enrolling roughly 1000 participants; the evaluation of each includes obtaining a detailed family and medical history, as well as a clinical evaluation. The participants are being consented broadly for research on many traits and for whole-genome sequencing. Initially, Sanger-based sequencing of 300–400 genes thought to be relevant to atherosclerosis is being performed, with the resulting data analyzed for rare, high-penetrance variants associated with specific clinical traits. The participants are also being consented to allow the contact of family members for additional studies of sequence variants to explore their potential association with specific phenotypes. Here, we present the general considerations in designing ClinSeq, preliminary results based on the generation of an initial 826 Mb of sequence data, the findings for several genes that serve as positive controls for the project, and our views about the potential implications of ClinSeq. The early experiences with ClinSeq illustrate how large-scale medical sequencing can be a practical, productive, and critical component of research in genomic medicine.Elucidating the sequence of the human genome (International Human Genome Sequencing Consortium 2001, 2004) and subsequent advances in DNA sequencing technologies (Mardis 2008) have the potential to dramatically improve the delivery of health care through the acquisition of genomic information about individual patients. However, much research will be needed to develop medical applications of genomics; for example, little is known about how to organize and implement large-scale medical sequencing (LSMS; i.e., systematic resequencing of human DNA) in a clinical context. Other approaches for applying high-throughput genomics to health care (e.g., assaying single-nucleotide polymorphisms and establishing gene-expression profiles) offer diagnostic promise; these are not further considered here, as our focus is on LSMS for studying the relationship of germline genomic variation to health and disease.We recently launched ClinSeq (http://genome.gov/20519355), a project that aims to apply LSMS within a clinical research environment to answer questions about the genetic basis of health, disease, and drug response. The application of genomic approaches (in particular LSMS) in a clinical research context is associated with a number of considerations that define key “dimensions” of any study: the number of subjects, the associated clinical data, and the breadth of genome covered (Fig. 1). Numerous detailed studies of single genes have been carried out; while often performed on many participants with significant amounts of phenotypic information, they are focused on a very small portion of the genome. The flurry of papers that describe recently generated whole-genome sequences (Levy et al. 2007; Bentley et al. 2008; Wang et al. 2008; Wheeler et al. 2008) has provided the first true individual genome sequences, including a modest amount of associated clinical data; however, the number of examples is small to date. Greater numbers are promised by the 1000 Genomes Project (http://www.1000genomes.org/), although no phenotypic information will be available for the individuals being studied. ClinSeq aims to model a more ideal study with respect to these three dimensions (Fig. 1), with the potential to further move toward the ultimate ideal as technology advances.Open in a separate windowFigure 1.A spatial conceptualization of research studies in genomic medicine. There are three key “dimensions” to consider when applying genomics to clinical research: genome breadth (the fraction of the genome that is interrogated), number of subjects or participants, and the associated clinical data about those individuals (including its depth, breadth, and rigor). While the ideal study would acquire whole-genome sequences from large numbers of extensively phenotyped subjects, this is currently impractical. Single-gene studies can involve a few or numerous subjects and extensive clinical data, but by definition involve the examination of only a single gene and thus occupy one wall of this space. The individual genomes that have recently been sequenced (Levy et al. 2007; Bentley et al. 2008; Wang et al. 2008; Wheeler et al. 2008) provide nearly complete genome breadth, but with limited clinical data; further, their limited subject numbers place them on another wall of this space. The 1000 Genomes Project (http://www.1000genomes.org/) is providing large subject numbers and extensive genome breadth, but no clinical data—positioning it on the floor of this space. ClinSeq aims to reside in the center of this space, having attributes of substantial subject size (n = 1000 initially), moderate genome breadth (∼400 genes initially, with plans for expanding this breadth), and substantial clinical data.The general aims of ClinSeq are to: (1) develop the infrastructure and approaches to acquire and analyze genome sequence from individual research participants; (2) pilot the use of LSMS to elucidate the genetic architecture underlying human traits; (3) provide an open, shared resource and environment for basic and clinical researchers to work collaboratively to perform research in genomic medicine; and (4) establish approaches for informed consent and the return of genetic information to subjects participating in LSMS studies. In pursuing these aims, our overriding goals include modeling whole-genome sequence acquisition in a manner that is practical for a clinical research setting, advancing our understanding of the genetic basis of important human diseases and traits, and establishing how to scale LSMS prior to the day when whole-genome sequencing becomes part of routine clinical practice. In this paper, we describe the ClinSeq study design, provide a snapshot of our very early data generation, and discuss the implications of this study for the nascent field of genomic medicine. 相似文献
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LAWRENCE S. LONG MD SUDHA VED MBBS FAAP JEFFREY L. KOH MD † 《Paediatric anaesthesia》2009,19(5):513-520
Objective: To describe the differences in intraoperative opioid dosing and associated outcomes in children with and without cerebral palsy (CP). Background: Previous work on children with cognitive impairment has suggested that they receive less intraoperative opioid than children without cognitive impairment. This finding may be due to a common concern that impaired children are hypersensitive to the adverse effects of opioids. Patterns in intraoperative opioid dosing have yet to be studied in children with motor impairment (e.g. CP). Methods: We examined the medical records of pediatric patients with CP who underwent orthopedic surgery over the last decade at our institution, as well as the records of a randomly selected group of pediatric orthopedic patients without CP (non‐CP). Outcome variables were intraoperative opioid dosing, postoperative intensive care unit (ICU) admission, and postoperative oxygen desaturation. We collected demographic, surgical, and medical data for covariate analysis. A stepwise multivariate regression was used for each outcome. Results: Seventy‐one (71) CP and 77 non‐CP charts were included in the study. CP children received significantly less intraoperative opioid (3.26 ± 3.01 μg·kg?1 fentanyl dose equivalents) than non‐CP children (4.58 ± 3.79 μg·kg?1) (P = 0.02), and this difference was corroborated by the regression analysis, which significantly associated CP with decreased opioid dosing (P < 0.001). In addition, intraoperative opioid dosing, but not CP, predicted ICU admission (odds ratio: 1.463, 95% CI: 1.042–2.054, P = 0.03) and postoperative oxygen desaturation (odds ratio: 1.174, 95% CI: 1.031–1.338, P = 0.02). Conclusions: Similar to prior research on children with cognitive impairment, a reduction in intraoperative opioid dosing was found in children with CP. Given the discrepant doses of intraoperative opioid between groups, it is unclear whether children with CP are at any greater risk for untoward opioid‐related events. 相似文献
1000.
RAJIV CHAUDHARY MBBS MRCPCH SATHEESH CHONAT MBBS HARSHA GOWDA MBBS MRCPCH † PAUL CLARKE MD FRCPCH MRCP DCH DCCH † ANNA CURLEY MBBS MD MA MRCPI 《Paediatric anaesthesia》2009,19(7):653-658
Background: Endotracheal intubation and laryngoscopy are frequently performed procedures in neonatal intensive care. These procedures represent profoundly painful stimuli and have been associated with laryngospasm, bronchospasm, hemodynamic changes, raised intracranial pressure and an increased risk of intracranial hemorrhage. These adverse changes can cause significant neonatal morbidity but may be attenuated by the use of suitable premedication.
Aims: To evaluate current practices for premedication use prior to elective intubation in UK tertiary neonatal units.
Methods: Telephone questionnaire survey of all 50 tertiary neonatal units in the UK.
Results: Ninety percent of units report the routine use of sedation prior to intubation and 82% of units routinely use a muscle relaxant. Morphine was the most commonly used sedative and suxamethonium was the most commonly used muscle relaxant. Approximately half of the units also used atropine during intubation. Seventy seven percent of units had a written policy for premedication. Ten percent of the units did not routinely use any sedatives or muscle relaxants for elective intubation.
Conclusions: In comparison with data from a 1998 survey, our study demonstrated an increase in the number of units that have adopted a written policy for premedication use, and in the number routinely using premedication drugs for elective intubation. There remains little consensus as to which drugs should be used and in what dose. 相似文献
Aims: To evaluate current practices for premedication use prior to elective intubation in UK tertiary neonatal units.
Methods: Telephone questionnaire survey of all 50 tertiary neonatal units in the UK.
Results: Ninety percent of units report the routine use of sedation prior to intubation and 82% of units routinely use a muscle relaxant. Morphine was the most commonly used sedative and suxamethonium was the most commonly used muscle relaxant. Approximately half of the units also used atropine during intubation. Seventy seven percent of units had a written policy for premedication. Ten percent of the units did not routinely use any sedatives or muscle relaxants for elective intubation.
Conclusions: In comparison with data from a 1998 survey, our study demonstrated an increase in the number of units that have adopted a written policy for premedication use, and in the number routinely using premedication drugs for elective intubation. There remains little consensus as to which drugs should be used and in what dose. 相似文献