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Pesquisa : A02.513.514.287 [Categoria DeCS]
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  1 / 574 MEDLINE  
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PMID:28455229
Autor:Wang B; Chen Z; Meng X; Li M; Yang X; Zhang C
Endereço:Department of Orthopedics, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191, China.
Título:iTRAQ quantitative proteomic study in patients with thoracic ossification of the ligamentum flavum.
Fonte:Biochem Biophys Res Commun; 487(4):834-839, 2017 06 10.
ISSN:1090-2104
País de publicação:United States
Idioma:eng
Resumo:Thoracic ossification of the ligamentum flavum (TOLF) is a unique disease with ectopic ossification, and is a major cause of thoracic spinal stenosis and myelopathy. However, the underlying etiology remains largely unknown. In this study, the ligamentum flavum was systematically analyzed in TOLF patients by using comprehensive iTRAQ labeled quantitative proteomics. Among 1285 detected proteins, there were 282 proteins identified to be differentially expressed. The Gene Ontology (GO) analysis regarding functional annotation of proteins consists of the following three aspects: the biological process, the molecular function, and the cellular components. The function clustering analysis revealed that ten of the above proteins are related to inflammation, such as tumor necrosis factor (TNF). This finding was subsequently validated by ELISA, which indicated that serum TNF-α of TOLF patients was significantly higher compared with the control group. To address the effect of TNF-α on ossification-related gene expression, we purified and cultured primary cells from thoracic ligamentum flavum of patients with TOLF. TNF-α was then used to stimulate cells. RNA was isolated and analyzed by RT-PCR. Our results showed that TNF-α was able to induce the expressions of osteoblast-specific transcription factor Osterix (Osx) in ligamentum flavum cells, suggesting that it can promote osteoblast differentiation. In addition, as the Osx downstream osteoblast genes OCN and ALP were also activated by TNF-α. This is the first proteomic study to identify inflammation factors such as TNF-α involved in ossified ligamentum flavum in TOLF, which may contribute to a better understanding of the cause of TOLF.
Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
Nome de substância:0 (Sp7 Transcription Factor); 0 (Sp7 protein, human); 0 (Transcription Factors); 0 (Tumor Necrosis Factor-alpha)


  2 / 574 MEDLINE  
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PMID:28669725
Autor:Sun C; Tian J; Liu X; Guan G
Endereço:Department of Spine Surgery, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 211100, China.
Título:MiR-21 promotes fibrosis and hypertrophy of ligamentum flavum in lumbar spinal canal stenosis by activating IL-6 expression.
Fonte:Biochem Biophys Res Commun; 490(3):1106-1111, 2017 Aug 26.
ISSN:1090-2104
País de publicação:United States
Idioma:eng
Resumo:The molecular mechanism underlying the fibrosis of ligamentum flavum(LF) in patients with lumbar spinal canal stenosis(LSCS) remains unknown. MicroRNAs are reported to play important roles in regulating fibrosis in different organs. The present study aimed to identify fibrosis related miR-21 expression profile and investigate the pathological process of miR-21 in the fibrosis of LF hypertrophy and associated regulatory mechanisms. 15 patients with LSCS underwent surgical treatment were enrolled in this study. For the control group, 11 patients with lumbar disc herniation(LDH) was included. The LF thickness was measured on MRI. LF samples were obtained during the surgery. Fibrosis score was assessed by Masson's trichrome staining. The expression of miR-21 in LF tissues were determined by RT-PCR. Correlation among LF thickness, fibrosis score, and miR-21 expression was analyzed. In addition, Lentiviral vectors for miR-21 mimic were constructed and transfected into LF cells to examine the role of miR-21 in LF fibrosis. Types I and III collagen were used as indicators of fibrosis. IL-6 expression in LF cells after transfection was investigated by RT-PCR and ELISA. Patients in two groups showed similar outcomes regarding age, gender, level of LF tissue. The thickness and fibrosis score of LF in the LSCS group were significantly greater than those in LDH group (all P < 0.05). Similarly, the expression of miR-21 in LSCS group was substantially higher than that in LDH group(P < 0.05). Furthermore, the miR-21 expression exhibited positive correlations with the LF thickness (r = 0.595, P < 0.05) and fibrosis score (r = 0.608, P < 0.05). Of note, miR-21 over-expression increased the expression levels of collagen I and III (P < 0.05). Also, IL-6 expression and secretion in LF cells was elevated after transfection of miR-21 mimic. MiR-21 is a fibrosis-associated miRNA and promotes inflammation in LF tissue by activating IL-6 expression, leading to LF fibrosis and hypertrophy.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Interleukin-6); 0 (MIRN21 microRNA, human); 0 (MicroRNAs)


  3 / 574 MEDLINE  
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PMID:28575129
Autor:Zhang C; Chen Z; Meng X; Li M; Zhang L; Huang A
Endereço:Department of Orthopedics, Peking University International Hospital, Beijing, China.
Título:The involvement and possible mechanism of pro-inflammatory tumor necrosis factor alpha (TNF-α) in thoracic ossification of the ligamentum flavum.
Fonte:PLoS One; 12(6):e0178986, 2017.
ISSN:1932-6203
País de publicação:United States
Idioma:eng
Resumo:Thoracic ossification of the ligamentum flavum (TOLF) is characterized by ectopic bone formation in the ligamentum flavum and is considered to be a leading cause of thoracic spinal canal stenosis and myelopathy. However, the underlying etiology is not well understood. An iTRAQ proteomics was used to reveal the involvement of inflammation factors in TOLF. TNF-α is a pro-inflammatory cytokine implicated in the pathogenesis of many human diseases. Protein profiling analysis showed that the protein level of TNF-α increased in the ossified ligamentum flavum of TOLF, which was confirmed by western blot. The effects of TNF-α on primary ligamentum flavum cells was examined. Cell proliferation assay demonstrated that primary cells from the ossified ligamentum flavum of TOLF grew faster than the control. Flow cytometry assay indicated that the proportions of cells in S phase of cell cycle of primary cells increased after TNF-α stimulation. To address the effect of TNF-α on gene expression, primary cells were derived from ligamentum flavum of TOLF patients. Culture cells were stimulated by TNF-α. RNA was isolated and analyzed by quantitative RT-PCR. G1/S-specific proteins cyclin D1 and c-Myc were upregulated after TNF-α stimulation. On the other hand, osteoblast differentiation related genes such as Bmp2 and Osterix (Osx) were upregulated in the presence of TNF-α. TNF-α activated Osx expression in a dose-dependent manner. Interestingly, a specific mitogen-activated protein kinase ERK inhibitor U0126, but not JNK kinase inhibitor SP600125, abrogated TNF-α activation of Osx expression. This suggests that TNF-α activates Osx expression through the mitogen-activated protein kinase ERK pathway. Taken together, we provide the evidence to support that TNF-α involves in TOLF probably through regulating cell proliferation via cyclin D1 and c-Myc, and promoting osteoblast differentiation via Osx.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Proto-Oncogene Proteins c-myc); 0 (Tumor Necrosis Factor-alpha); 136601-57-5 (Cyclin D1)


  4 / 574 MEDLINE  
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PMID:28511807
Autor:Hyldmo PK; Horodyski M; Conrad BP; Aslaksen S; Røislien J; Prasarn M; Rechtine GR; Søreide E
Endereço:Department of Research, Norwegian Air Ambulance Foundation, Drøbak, Norway; Trauma Unit, Sørlandet Hospital, Kristiansand, Norway. Electronic address: pkh@sshf.no.
Título:Does the novel lateral trauma position cause more motion in an unstable cervical spine injury than the logroll maneuver?
Fonte:Am J Emerg Med; 35(11):1630-1635, 2017 Nov.
ISSN:1532-8171
País de publicação:United States
Idioma:eng
Resumo:OBJECTIVE: Prehospital personnel who lack advanced airway management training must rely on basic techniques when transporting unconscious trauma patients. The supine position is associated with a loss of airway patency when compared to lateral recumbent positions. Thus, an inherent conflict exists between securing an open airway using the recovery position and maintaining spinal immobilization in the supine position. The lateral trauma position is a novel technique that aims to combine airway management with spinal precautions. The objective of this study was to compare the spinal motion allowed by the novel lateral trauma position and the well-established log-roll maneuver. METHODS: Using a full-body cadaver model with an induced globally unstable cervical spine (C5-C6) lesion, we investigated the mean range of motion (ROM) produced at the site of the injury in six dimensions by performing the two maneuvers using an electromagnetic tracking device. RESULTS: Compared to the log-roll maneuver, the lateral trauma position caused similar mean ROM in five of the six dimensions. Only medial/lateral linear motion was significantly greater in the lateral trauma position (1.4mm (95% confidence interval [CI] 0.4, 2.4mm)). CONCLUSIONS: In this cadaver study, the novel lateral trauma position and the well-established log-roll maneuver resulted in comparable amounts of motion in an unstable cervical spine injury model. We suggest that the lateral trauma position may be considered for unconscious non-intubated trauma patients.
Tipo de publicação: JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL


  5 / 574 MEDLINE  
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PMID:28385821
Autor:Nouri A; Fehlings MG
Endereço:Spinal Cord Injury Clinical Research Unit (Nouri), Toronto Western Hospital, University Health Network; Division of Neurosurgery, Department of Surgery, and Spinal Program (Fehlings), University of Toronto, Toronto, Ont.
Título:Diffuse idiopathic skeletal hyperostosis with cervical myelopathy.
Fonte:CMAJ; 189(10):E410, 2017 03 13.
ISSN:1488-2329
País de publicação:Canada
Idioma:eng
Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE


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PMID:28339441
Autor:Kim YU; Park JY; Kim DH; Karm MH; Lee JY; Yoo JI; Chon SW; Suh JH
Endereço:University Seoul, Republic of Korea.
Título:The Role of the Ligamentum Flavum Area as a Morphological Parameter of Lumbar Central Spinal Stenosis.
Fonte:Pain Physician; 20(3):E419-E424, 2017 Mar.
ISSN:2150-1149
País de publicação:United States
Idioma:eng
Resumo:BACKGROUND: Hypertrophy of the ligamentum flavum (LF) has been considered as a major cause of lumbar central spinal stenosis (LCSS). Previous studies have found that ligamentum flavum thickness (LFT) is correlated with aging, disc degeneration, and lumbar spinal stenosis. However, hypertrophy is different from thickness. Thus, to evaluate hypertrophy of the whole LF, we devised a new morphological parameter, called the ligamentum flavum area (LFA). OBJECTIVES: We hypothesized that the LFA is a key morphologic parameter in the diagnosis of LCSS. STUDY DESIGN: Retrospective observational study. SETTING: The single center study in Seoul, Republic of Korea. METHODS: LF samples were collected from 166 patients with LCSS, and from 167 controls who underwent lumbar magnetic resonance imaging (MRI) as part of a routine medical examination. T1-weighted axial MR imageswere acquired at the facet joint level from individual patients. We measured the LFA and LFT at the L4-L5 intervertebral level on MRI using a picture archiving and communications system. The LFA was measured as the cross-sectional area of the whole LF at the L4-L5 stenotic level. The LFT was measured by drawing a line along the side of the ligament facing the spinal canal and along the laminar side of the ligament curve and then measuring the thickest point at the L4-L5 level. RESULTS: The average LFA was 96.56 ± 30.74 mm2 in the control group and 132.69 ± 32.68 mm2 in the LCSS group. The average LFT was 3.61 ± 0.72 mm in the control group and 4.24 ± 0.97 mm in the LCSS group. LCSS patients had significantly higher LFA (P < 0.001) and LFT (P < 0.001). Regarding the validity of both LFA and LFT as predictors of LCSS, Receiver Operator Characteristics (ROC) curve analysis showed that the best cut-off point for the LFA was 105.90 mm2, with 80.1% sensitivity, 76.0% specificity, and area under the curve (AUC) of 0.83 (95% CI, 0.78 - 0.87). The best cut off-point of the LFT was 3.74 mm, with 70.5% sensitivity, 66.5% specificity, and AUC of 0.72 (95% CI, 0.66 - 0.77). LIMITATIONS: The principal methodological limitation was the retrospective observational nature. Anatomically, degenerative lumbar spinal stenosis can involve the central canal, foramina, and lateral recess. However, we focused on LCSS only. CONCLUSIONS: Although the LFT and LFA were both significantly associated with LCSS, the LFA was a more sensitive measurement parameter. Thus, to evaluate LCSS patients, the treating doctor should more carefully analyze the LFA than LFT.Institutional Review Board (IRB) approval number: S2015-1328-0001Key words: Ligamentum flavum, ligamentum flavum area, ligamentum flavum thickness, lumbar central spinal stenosis, hypertrophy of the ligamentum flavum, morphological parameter, cross-sectional area, optimal cut-off point.
Tipo de publicação: JOURNAL ARTICLE


  7 / 574 MEDLINE  
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PMID:28060908
Autor:Saito T; Yokota K; Kobayakawa K; Hara M; Kubota K; Harimaya K; Kawaguchi K; Hayashida M; Matsumoto Y; Doi T; Shiba K; Nakashima Y; Okada S
Endereço:Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Título:Experimental Mouse Model of Lumbar Ligamentum Flavum Hypertrophy.
Fonte:PLoS One; 12(1):e0169717, 2017.
ISSN:1932-6203
País de publicação:United States
Idioma:eng
Resumo:Lumbar spinal canal stenosis (LSCS) is one of the most common spinal disorders in elderly people, with the number of LSCS patients increasing due to the aging of the population. The ligamentum flavum (LF) is a spinal ligament located in the interior of the vertebral canal, and hypertrophy of the LF, which causes the direct compression of the nerve roots and/or cauda equine, is a major cause of LSCS. Although there have been previous studies on LF hypertrophy, its pathomechanism remains unclear. The purpose of this study is to establish a relevant mouse model of LF hypertrophy and to examine disease-related factors. First, we focused on mechanical stress and developed a loading device for applying consecutive mechanical flexion-extension stress to the mouse LF. After 12 weeks of mechanical stress loading, we found that the LF thickness in the stress group was significantly increased in comparison to the control group. In addition, there were significant increases in the area of collagen fibers, the number of LF cells, and the gene expression of several fibrosis-related factors. However, in this mecnanical stress model, there was no macrophage infiltration, angiogenesis, or increase in the expression of transforming growth factor-ß1 (TGF-ß1), which are characteristic features of LF hypertrophy in LSCS patients. We therefore examined the influence of infiltrating macrophages on LF hypertrophy. After inducing macrophage infiltration by micro-injury to the mouse LF, we found excessive collagen synthesis in the injured site with the increased TGF-ß1 expression at 2 weeks after injury, and further confirmed LF hypertrophy at 6 weeks after injury. Our findings demonstrate that mechanical stress is a causative factor for LF hypertrophy and strongly suggest the importance of macrophage infiltration in the progression of LF hypertrophy via the stimulation of collagen production.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (RNA, Messenger); 9007-34-5 (Collagen)


  8 / 574 MEDLINE  
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PMID:28004120
Autor:Ning S; Chen Z; Fan D; Sun C; Zhang C; Zeng Y; Li W; Hou X; Qu X; Ma Y; Yu H
Endereço:Department of Orthopedics, Peking University Third Hospital, Beijing 100191, P.R. China.
Título:Genetic differences in osteogenic differentiation potency in the thoracic ossification of the ligamentum flavum under cyclic mechanical stress.
Fonte:Int J Mol Med; 39(1):135-143, 2017 Jan.
ISSN:1791-244X
País de publicação:Greece
Idioma:eng
Resumo:Mechanical stress and genetic factors play important roles in the occurrence of thoracic ossification of ligament flavum (TOLF), which can occur at one, two, or multiple levels of the spine. It is unclear whether single- and multiple-level TOLF differ in terms of osteogenic differentiation potency and osteogenesis-related gene expression under cyclic mechanical stress. This was addressed in the present study using patients with non­TOLF and single­ and multiple­level TOLF (n=8 per group). Primary ligament cells were cultured and osteogenesis was induced by application of cyclic mechanical stress. Osteogenic differentiation was assessed by evaluating alkaline phosphatase (ALP) activity and the mRNA and protein expression of osteogenesis­related genes, including ALP, bone morphogenetic protein 2 (BMP2), Runt­related transcription factor­2 (Runx­2), osterix, osteopontin (OPN) and osteocalcin. The application of cyclic mechanical stress resulted in higher ALP activity in the multiple­level than in the single­level TOLF group, whereas no changes were observed in the non­TOLF group. The ALP, BMP2, OPN and osterix mRNA levels were higher in the multiple­level as compared to the single­level TOLF group, and the levels of all osteogenesis-related genes, apart from Runx2, were higher in the multiple­level as compared to the non­TOLF group. The osterix and ALP protein levels were higher in the multiple­level TOLF group than in the other 2 groups, and were increased with the longer duration of stress. These results highlight the differences in osteogenic differentiation potency between single­ and multiple­level TOLF that may be related to the different pathogenesis and genetic background.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Biomarkers); 0 (RNA, Messenger); EC 3.1.3.1 (Alkaline Phosphatase)


  9 / 574 MEDLINE  
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PMID:27580526
Autor:Sakai Y; Ito S; Hida T; Ito K; Harada A; Watanabe K
Endereço:National Center for Geriatric and Gerontology, Department of Orthopaedic Surgery, Japan. Electronic address: jsakai@ncgg.go.jp.
Título:Clinical outcome of lumbar spinal stenosis based on new classification according to hypertrophied ligamentum flavum.
Fonte:J Orthop Sci; 22(1):27-33, 2017 Jan.
ISSN:1436-2023
País de publicação:Japan
Idioma:eng
Resumo:BACKGROUND: The ligamentum flavum hypertrophy is considered to be one of the important causes of development of lumbar spinal stenosis (LSS). Several histologic and biologic mechanisms in hypertrophied flavum have proposed. However, no study that investigated the relationship between clinical outcome and ligamentum flavum hypertrophy has been published. The purpose of this study was to identify a new classification of LSS, in ligamentous and nonligamentous stenosis, according to the cutoff value of the area proportion of the ligamentum flavum in the spinal canal, and to assess the value of surgical and conservative treatments for LSS based on the classification of the ligamentous stenosis. METHODS: A total of 230 surgical patients with LSS were evaluated based on the cross-sectional area and intraoperative findings of the ligamentum flavum. LSS was classified as ligamentous or nonligamentous stenosis, according to the cutoff value of the proportion of the ligamentum flavum in the spinal canal. Based on the classification, the results of 234 surgical patients (103 patients with spinal fusion surgery and 131 patients with spinal decompression) and 191 patients under conservative treatment with prostaglandin E1 were evaluated, 1 year after treatments. RESULTS: ROC analysis revealed that the area under the curve for the cutoff value of the proportion of the ligamentum flavum in the spinal canal was 0.4275 (sensitivity = 0.861, specificity = 0.854). Based on these criteria, ligamentous and nonligamentous stenoses were 115 and 119 in surgical patients, 97 and 94 in conservative patients, respectively. In the surgical treatment group, no significant difference was found in any of the evaluations conducted for the group with ligamentous and nonligamentous stenosis. However, in the conservative treatment group, the patients with ligamentous stenosis showed significant improvement compared with patients with nonligamentous stenosis. CONCLUSIONS: Ligamentous stenosis in LSS patients had favorable outcome on conservative treatment with prostaglandin E1 derivative.
Tipo de publicação: JOURNAL ARTICLE


  10 / 574 MEDLINE  
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PMID:27548012
Autor:Eun SS; Kumar R; Choi WG; Cho HR; Lee SH
Endereço:Department of Orthopaedics, Spine Health Wooridul Hospital, Gangnam-gu, Seoul, the Republic of Korea.
Título:Lamina Fenestration Technique for Treatment of Thoracic Ossified Ligamentum Flavum: 2-Year Follow-Up Result.
Fonte:J Neurol Surg A Cent Eur Neurosurg; 78(3):286-290, 2017 May.
ISSN:2193-6323
País de publicação:Germany
Idioma:eng
Resumo:The incidence of thoracic ossification of ligamentum flavum (OLF) is increasing, and the available surgical techniques were invasive. To evaluate the surgical outcome and prognostic factors in relation to clinicoradiologic variables with a novel minimally invasive lamina fenestration technique in patients with thoracic OLF. Between July 2005 and November 2010, 27 levels with 50 lesions in 17 patients were treated with the lamina fenestration technique for the decompression of thoracic OLF. This technique creates a keyhole in the lamina, preserving lower lamina bone, facet joint, and ligamentum flavum. Patient outcome was analyzed using the Japanese Orthopaedic Association (JOA) score and progression of kyphosis on simple X-ray. All patients were successfully treated with the laminar fenestration technique. There was one dural tear but no neural complication or injury. Mean length of follow-up was 49 months. Mean JOA score improved from 4.88 to 7 ( = 0.000). Six patients had an excellent surgical outcome; 10 had a good surgical outcome according to JOA scoring. The lamina fenestration technique for the treatment of thoracic OLF had a successful outcome with few complications. This technique can be a minimally invasive surgical option for the treatment of thoracic OLF.
Tipo de publicação: JOURNAL ARTICLE



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