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Article ; Online: Three-dimensional EOS Analysis of Apical Vertebral Rotation in Adolescent Idiopathic Scoliosis.

Kato, So / Debaud, Charlotte / Zeller, Reinhard D

2017 Volume 37, Issue 8, Page(s) e543–e547

Abstract: Background: Apical vertebral rotation (AVR) is increasingly recognized as one of the important radiographic parameters in adolescent idiopathic scoliosis (AIS). EOS enables us to precisely measure AVR by 3-dimensional reconstruction. The objective of ... ...

Abstract	Background: Apical vertebral rotation (AVR) is increasingly recognized as one of the important radiographic parameters in adolescent idiopathic scoliosis (AIS). EOS enables us to precisely measure AVR by 3-dimensional reconstruction. The objective of the present study was to describe the postoperative correction and the long-term follow-up of AVR in posterior spinal fusion with direct vertebral rotation and elucidate the factors that affected the correction. Methods: We retrospectively reviewed 153 consecutive posterior spinal fusion surgeries for AIS performed between 2009 and 2012. Among them, 55 patients who fulfilled the study inclusion criteria with complete preoperative, immediate postoperative, and last follow-up (>1 y) EOS images were included in the present study. EOS 3-dimentional reconstructions were undertaken for each patient. Postoperative AVR correction and the loss of correction were calculated. Results: Preoperative AVR of the major curve averaged 19 degrees (SD=7 degrees), and AVR on immediate postoperative images averaged 9 degrees (SD=6 degrees, P<0.001). AVR at final follow-up averaged 11 degrees (SD=6 degrees, P=0.06). Postoperative correction was larger in all-screw construct than in hybrid construct (55% vs. 36%, P=0.03). Conclusions: The present study is the first study to measure AVR in a large population of AIS patients using EOS 3-dimensional reconstruction. We report the correction magnitude was significantly affected by the construct. Level of evidence: Level IV-therapeutic study (case series).
Language	English
Publishing date	2017-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	604642-3
ISSN	1539-2570 ; 0271-6798
ISSN (online)	1539-2570
ISSN	0271-6798
DOI	10.1097/BPO.0000000000000776
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Article ; Online: Local and Systemic Factors Drive Ectopic Osteogenesis in Regenerating Muscles of Spinal-Cord-Injured Mice in a Lesion-Level-Dependent Manner.

Debaud, Charlotte / Tseng, Hsu-Wen / Chedik, Malha / Kulina, Irina / Genêt, François / Ruitenberg, Marc J / Levesque, Jean-Pierre

Journal of neurotrauma

2021 Volume 38, Issue 15, Page(s) 2162–2175

Abstract: Neuroimmune dysfunction is thought to promote the development of several acute and chronic complications in spinal cord injury (SCI) patients. Putative roles for adrenal stress hormones and catecholamines are increasingly being recognized, yet how these ... ...

Abstract	Neuroimmune dysfunction is thought to promote the development of several acute and chronic complications in spinal cord injury (SCI) patients. Putative roles for adrenal stress hormones and catecholamines are increasingly being recognized, yet how these adversely affect peripheral tissue homeostasis and repair under SCI conditions remains elusive. Here, we investigated their influence in a mouse model of SCI with acquired neurogenic heterotopic ossification. We show that spinal cord lesions differentially influence muscular regeneration in a level-dependent manner and through a complex multi-step process that creates an osteopermissive environment within the first hours of injury. This cascade of events is shown to critically involve adrenergic signals and drive the acute release of the neuropeptide, substance P. Our findings generate new insights into the kinetics and processes that govern SCI-induced deregulations in skeletal muscle homeostasis and regeneration, thereby aiding the development of sequential therapeutic strategies that can prevent or attenuate neuromusculoskeletal complications in SCI patients.
MeSH term(s)	Animals ; Disease Models, Animal ; Female ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal/pathology ; Ossification, Heterotopic/etiology ; Ossification, Heterotopic/pathology ; Regeneration/physiology ; Spinal Cord Injuries/complications ; Spinal Cord Injuries/pathology
Language	English
Publishing date	2021-06-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645092-1
ISSN	1557-9042 ; 0897-7151
ISSN (online)	1557-9042
ISSN	0897-7151
DOI	10.1089/neu.2021.0058
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Zs.A 2016: Show issues

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Article ; Online: Bacterial Lipopolysaccharides Exacerbate Neurogenic Heterotopic Ossification Development.

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2023 Volume 38, Issue 11, Page(s) 1700–1717

Abstract: Neurogenic heterotopic ossifications (NHO) are heterotopic bones that develop in periarticular muscles after severe central nervous system (CNS) injuries. Several retrospective studies have shown that NHO prevalence is higher in patients who suffer ... ...

Abstract	Neurogenic heterotopic ossifications (NHO) are heterotopic bones that develop in periarticular muscles after severe central nervous system (CNS) injuries. Several retrospective studies have shown that NHO prevalence is higher in patients who suffer concomitant infections. However, it is unclear whether these infections directly contribute to NHO development or reflect the immunodepression observed in patients with CNS injury. Using our mouse model of NHO induced by spinal cord injury (SCI) between vertebrae T
MeSH term(s)	Mice ; Animals ; Humans ; Lipopolysaccharides/pharmacology ; Retrospective Studies ; Spinal Cord Injuries/complications ; Ossification, Heterotopic/pathology ; Bacteria ; Minerals
Chemical Substances	Lipopolysaccharides ; Minerals
Language	English
Publishing date	2023-09-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1002/jbmr.4905
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Zs.A 2142: Show issues

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Article ; Online: Blocking neuromuscular junctions with botulinum toxin A injection enhances neurological heterotopic ossification development after spinal cord injury in mice.

Salga, Marjorie / Tseng, Hsu-Wen / Alexander, Kylie A / Jose, Beulah / Vaquette, Cedryck / Debaud, Charlotte / Gatin, Laure / Genêt, François / Levesque, Jean-Pierre

Annals of physical and rehabilitation medicine

2019 Volume 62, Issue 3, Page(s) 189–192

MeSH term(s)	Animals ; Botulinum Toxins, Type A/adverse effects ; Botulinum Toxins, Type A/pharmacology ; Disease Models, Animal ; Female ; Hamstring Muscles/drug effects ; Mice ; Mice, Inbred C57BL ; Neuromuscular Agents/adverse effects ; Neuromuscular Agents/pharmacology ; Neuromuscular Junction/drug effects ; Ossification, Heterotopic/chemically induced ; Spinal Cord Injuries/drug therapy
Chemical Substances	Neuromuscular Agents ; Botulinum Toxins, Type A (EC 3.4.24.69)
Language	English
Publishing date	2019-02-01
Publishing country	Netherlands
Document type	Letter
ZDB-ID	2480363-7
ISSN	1877-0665 ; 1877-0657
ISSN (online)	1877-0665
ISSN	1877-0657
DOI	10.1016/j.rehab.2019.01.005
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Zs.B 1857: Show issues

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Article ; Online: Recurrence of heterotopic ossification after removal in patients with traumatic brain injury: A systematic review.

Almangour, Waleed / Schnitzler, Alexis / Salga, Marjorie / Debaud, Charlotte / Denormandie, Philippe / Genêt, François

Annals of physical and rehabilitation medicine

2016 Volume 59, Issue 4, Page(s) 263–269

Abstract: Objective: A systematic review of the literature to determine whether in patients with neurological heterotopic ossification (NHO) after traumatic brain injury, the extent of the neurological sequelae, the timing of surgery and the extent of the initial ...

Abstract	Objective: A systematic review of the literature to determine whether in patients with neurological heterotopic ossification (NHO) after traumatic brain injury, the extent of the neurological sequelae, the timing of surgery and the extent of the initial NHO affect the risk of NHO recurrence. Data sources: We searched MEDLINE via PubMed and Cochrane library for articles published up to June 2015. Results were compared with epidemiological studies using data from the BANKHO database of 357 patients with central nervous system (CNS) lesions who underwent 539 interventions for troublesome HO. Results: A large number of studies were published in the 1980s and 1990s, most showing poor quality despite being performed by experienced surgical teams. Accordingly, results were contradictory and practices heterogeneous. Results with the BANKHO data showed troublesome NHO recurrence not associated with aetiology, sex, age at time of CNS lesion, multisite HO, or "early" surgery (before 6months). Equally, recurrence was not associated with neurological sequelae or disease extent around the joint. Conclusions: The recurrence of NHO is not affected by delayed surgery, neurological sequelae or disease extent around the joint. Surgical excision of NHO should be performed as soon as comorbid factors are under control and the NHO is sufficiently constituted for excision.
MeSH term(s)	Adult ; Brain Injuries, Traumatic/complications ; Brain Injuries, Traumatic/surgery ; Female ; Humans ; Male ; Middle Aged ; Neurosurgical Procedures ; Ossification, Heterotopic/etiology ; Ossification, Heterotopic/pathology ; Ossification, Heterotopic/surgery ; Postoperative Complications/etiology ; Postoperative Complications/pathology ; Recurrence
Language	English
Publishing date	2016-09
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2480363-7
ISSN	1877-0665 ; 1877-0657
ISSN (online)	1877-0665
ISSN	1877-0657
DOI	10.1016/j.rehab.2016.03.009
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Article ; Online: Peripheral denervation participates in heterotopic ossification in a spinal cord injury model.

Debaud, Charlotte / Salga, Marjorie / Begot, Laurent / Holy, Xavier / Chedik, Malha / de l'Escalopier, Nicolas / Torossian, Fréderic / Levesque, Jean-Pierre / Lataillade, Jean-Jacques / Le Bousse-Kerdilès, Marie-Caroline / Genêt, François

PloS one

2017 Volume 12, Issue 8, Page(s) e0182454

Abstract: We previously reported the development of a new acquired neurogenic HO (NHO) mouse model, combining spinal cord transection (SCI) and chemical muscle injury. Pathological mechanisms responsible for ectopic osteogenesis after central neurological damage ... ...

Abstract	We previously reported the development of a new acquired neurogenic HO (NHO) mouse model, combining spinal cord transection (SCI) and chemical muscle injury. Pathological mechanisms responsible for ectopic osteogenesis after central neurological damage are still to be elucidated. In this study, we first hypothesized that peripheral nervous system (PNS) might convey pathological signals from injured spinal cord to muscles in NHO mouse model. Secondly, we sought to determine whether SCI could lead to intramuscular modifications of BMP2 signaling pathways. Twenty one C57Bl6 mice were included in this protocol. Bilateral cardiotoxin (CTX) injection in hamstring muscles was associated with a two-stage surgical procedure, combining thoracic SCI with unilateral peripheral denervation. Volumes of HO (Bone Volume, BV) were measured 28 days after surgery using micro-computed tomography imaging techniques and histological analyses were made to confirm intramuscular osteogenesis. Volume comparisons were conducted between right and left hind limb of each animal, using a Wilcoxon signed rank test. Quantitative polymerase chain reaction (qPCR) was performed to explore intra muscular expression of BMP2, Alk3 and Id1. Nineteen mice survive the complete SCI and peripheral denervation procedure. When CTX injections were done right after surgery (n = 7), bilateral HO were detected in all animals after 28 days. Micro-CT measurements showed significantly increased BV in denervated paws (1.47 mm3 +/- 0.5) compared to contralateral sides (0.56 mm3 +/-0.4), p = 0.03. When peripheral denervation and CTX injections were performed after sham SCI surgery (n = 6), bilateral HO were present in three mice at day 28. Quantitative PCR analyses showed no changes in intra muscular BMP2 expression after SCI as compared to control mice (shamSCI). Peripheral denervation can be reliably added to spinal cord transection in NHO mouse model. This new experimental design confirms that neuro inflammatory mechanisms induced by central or peripheral nervous system injury plays a key role in triggering ectopic osteogenesis.
MeSH term(s)	Animals ; Bone Morphogenetic Protein 2/analysis ; Cobra Cardiotoxin Proteins ; Denervation ; Disease Models, Animal ; Female ; Mice, Inbred C57BL ; Muscles/drug effects ; Muscles/innervation ; Muscles/pathology ; Ossification, Heterotopic/chemically induced ; Ossification, Heterotopic/diagnostic imaging ; Ossification, Heterotopic/etiology ; Ossification, Heterotopic/pathology ; Spinal Cord/diagnostic imaging ; Spinal Cord/drug effects ; Spinal Cord/pathology ; Spinal Cord Injuries/chemically induced ; Spinal Cord Injuries/diagnostic imaging ; Spinal Cord Injuries/etiology ; Spinal Cord Injuries/pathology ; X-Ray Microtomography
Chemical Substances	Bone Morphogenetic Protein 2 ; Cobra Cardiotoxin Proteins
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0182454
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Article ; Online: Peripheral denervation participates in heterotopic ossification in a spinal cord injury model.

Charlotte Debaud / Marjorie Salga / Laurent Begot / Xavier Holy / Malha Chedik / Nicolas de l'Escalopier / Fréderic Torossian / Jean-Pierre Levesque / Jean-Jacques Lataillade / Marie-Caroline Le Bousse-Kerdilès / François Genêt

PLoS ONE, Vol 12, Iss 8, p e

2017 Volume 0182454

Abstract	We previously reported the development of a new acquired neurogenic HO (NHO) mouse model, combining spinal cord transection (SCI) and chemical muscle injury. Pathological mechanisms responsible for ectopic osteogenesis after central neurological damage are still to be elucidated. In this study, we first hypothesized that peripheral nervous system (PNS) might convey pathological signals from injured spinal cord to muscles in NHO mouse model. Secondly, we sought to determine whether SCI could lead to intramuscular modifications of BMP2 signaling pathways. Twenty one C57Bl6 mice were included in this protocol. Bilateral cardiotoxin (CTX) injection in hamstring muscles was associated with a two-stage surgical procedure, combining thoracic SCI with unilateral peripheral denervation. Volumes of HO (Bone Volume, BV) were measured 28 days after surgery using micro-computed tomography imaging techniques and histological analyses were made to confirm intramuscular osteogenesis. Volume comparisons were conducted between right and left hind limb of each animal, using a Wilcoxon signed rank test. Quantitative polymerase chain reaction (qPCR) was performed to explore intra muscular expression of BMP2, Alk3 and Id1. Nineteen mice survive the complete SCI and peripheral denervation procedure. When CTX injections were done right after surgery (n = 7), bilateral HO were detected in all animals after 28 days. Micro-CT measurements showed significantly increased BV in denervated paws (1.47 mm3 +/- 0.5) compared to contralateral sides (0.56 mm3 +/-0.4), p = 0.03. When peripheral denervation and CTX injections were performed after sham SCI surgery (n = 6), bilateral HO were present in three mice at day 28. Quantitative PCR analyses showed no changes in intra muscular BMP2 expression after SCI as compared to control mice (shamSCI). Peripheral denervation can be reliably added to spinal cord transection in NHO mouse model. This new experimental design confirms that neuro inflammatory mechanisms induced by central or peripheral nervous system injury plays a key role in triggering ectopic osteogenesis.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Macrophage-derived oncostatin M contributes to human and mouse neurogenic heterotopic ossifications.

Torossian, Frédéric / Guerton, Bernadette / Anginot, Adrienne / Alexander, Kylie A / Desterke, Christophe / Soave, Sabrina / Tseng, Hsu-Wen / Arouche, Nassim / Boutin, Laetitia / Kulina, Irina / Salga, Marjorie / Jose, Beulah / Pettit, Allison R / Clay, Denis / Rochet, Nathalie / Vlachos, Erica / Genet, Guillaume / Debaud, Charlotte / Denormandie, Philippe /

Genet, François / Sims, Natalie A / Banzet, Sébastien / Levesque, Jean-Pierre / Lataillade, Jean-Jacques / Le Bousse-Kerdilès, Marie-Caroline

JCI insight

2017 Volume 2, Issue 21

Abstract: Neurogenic heterotopic ossification (NHO) is the formation of ectopic bone generally in muscles surrounding joints following spinal cord or brain injury. We investigated the mechanisms of NHO formation in 64 patients and a mouse model of spinal cord ... ...

Abstract	Neurogenic heterotopic ossification (NHO) is the formation of ectopic bone generally in muscles surrounding joints following spinal cord or brain injury. We investigated the mechanisms of NHO formation in 64 patients and a mouse model of spinal cord injury-induced NHO. We show that marrow from human NHOs contains hematopoietic stem cell (HSC) niches, in which mesenchymal stromal cells (MSCs) and endothelial cells provide an environment supporting HSC maintenance, proliferation, and differentiation. The transcriptomic signature of MSCs from NHOs shows a neuronal imprinting associated with a molecular network required for HSC support. We demonstrate that oncostatin M (OSM) produced by activated macrophages promotes osteoblastic differentiation and mineralization of human muscle-derived stromal cells surrounding NHOs. The key role of OSM was confirmed using an experimental model of NHO in mice defective for the OSM receptor (OSMR). Our results provide strong evidence that macrophages contribute to NHO formation through the osteogenic action of OSM on muscle cells within an inflammatory context and suggest that OSM/OSMR could be a suitable therapeutic target. Altogether, the evidence of HSCs in ectopic bones growing at the expense of soft tissue in spinal cord/brain-injured patients indicates that inflammation and muscle contribute to HSC regulation by the brain-bone-blood triad.
MeSH term(s)	Animals ; Antigens, CD34 ; Brain Injuries ; Cell Differentiation ; Cell Proliferation ; Endothelial Cells ; Female ; Hematopoiesis ; Hematopoietic Stem Cells ; Heterografts ; Humans ; Macrophages/metabolism ; Mesenchymal Stem Cells ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Oncostatin M/metabolism ; Oncostatin M Receptor beta Subunit ; Ossification, Heterotopic/immunology ; Ossification, Heterotopic/metabolism ; Ossification, Heterotopic/pathology ; Osteogenesis ; Spinal Cord ; Transcriptome
Chemical Substances	Antigens, CD34 ; OSMR protein, human ; Oncostatin M Receptor beta Subunit ; Oncostatin M (106956-32-5)
Language	English
Publishing date	2017-11-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.96034
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