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1.
Lancet ; 396(10252): 684-692, 2020 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-32891212

RESUMO

BACKGROUND: There are no effective therapies for achondroplasia. An open-label study suggested that vosoritide administration might increase growth velocity in children with achondroplasia. This phase 3 trial was designed to further assess these preliminary findings. METHODS: This randomised, double-blind, phase 3, placebo-controlled, multicentre trial compared once-daily subcutaneous administration of vosoritide with placebo in children with achondroplasia. The trial was done in hospitals at 24 sites in seven countries (Australia, Germany, Japan, Spain, Turkey, the USA, and the UK). Eligible patients had a clinical diagnosis of achondroplasia, were ambulatory, had participated for 6 months in a baseline growth study and were aged 5 to less than 18 years at enrolment. Randomisation was done by means of a voice or web-response system, stratified according to sex and Tanner stage. Participants, investigators, and trial sponsor were masked to group assignment. Participants received either vosoritide 15·0 µg/kg or placebo, as allocated, for the duration of the 52-week treatment period administered by daily subcutaneous injections in their homes by trained caregivers. The primary endpoint was change from baseline in mean annualised growth velocity at 52 weeks in treated patients as compared with controls. All randomly assigned patients were included in the efficacy analyses (n=121). All patients who received one dose of vosoritide or placebo (n=121) were included in the safety analyses. The trial is complete and is registered, with EudraCT, number, 2015-003836-11. FINDINGS: All participants were recruited from Dec 12, 2016, to Nov 7, 2018, with 60 assigned to receive vosoritide and 61 to receive placebo. Of 124 patients screened for eligibility, 121 patients were randomly assigned, and 119 patients completed the 52-week trial. The adjusted mean difference in annualised growth velocity between patients in the vosoritide group and placebo group was 1·57 cm/year in favour of vosoritide (95% CI [1·22-1·93]; two-sided p<0·0001). A total of 119 patients had at least one adverse event; vosoritide group, 59 (98%), and placebo group, 60 (98%). None of the serious adverse events were considered to be treatment related and no deaths occurred. INTERPRETATION: Vosoritide is an effective treatment to increase growth in children with achondroplasia. It is not known whether final adult height will be increased, or what the harms of long-term therapy might be. FUNDING: BioMarin Pharmaceutical.


Assuntos
Acondroplasia/tratamento farmacológico , Peptídeo Natriurético Tipo C/análogos & derivados , Osteogênese , Absorciometria de Fóton , Acondroplasia/sangue , Adolescente , Biomarcadores/sangue , Estatura , Densidade Óssea , Criança , Pré-Escolar , Colágeno Tipo X/sangue , Método Duplo-Cego , Feminino , Humanos , Reação no Local da Injeção , Injeções Subcutâneas , Masculino , Peptídeo Natriurético Tipo C/uso terapêutico
2.
Genet Med ; 23(12): 2443-2447, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34341520

RESUMO

PURPOSE: Achondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported. METHODS: After completing at least six months of a baseline observational growth study, and 52 weeks in a double-blind, placebo-controlled study, participants were eligible to continue treatment in an open-label extension study, where all participants received vosoritide at a dose of 15.0 µg/kg/day. RESULTS: In children randomized to vosoritide, annualized growth velocity increased from 4.26 cm/year at baseline to 5.39 cm/year at 52 weeks and 5.52 cm/year at week 104. In children who crossed over from placebo to vosoritide in the extension study, annualized growth velocity increased from 3.81 cm/year at week 52 to 5.43 cm/year at week 104. No new adverse effects of vosoritide were detected. CONCLUSION: Vosoritide treatment has safe and persistent growth-promoting effects in children with achondroplasia treated daily for two years.


Assuntos
Acondroplasia , Peptídeo Natriurético Tipo C , Acondroplasia/tratamento farmacológico , Acondroplasia/genética , Criança , Método Duplo-Cego , Humanos , Peptídeo Natriurético Tipo C/análogos & derivados , Peptídeo Natriurético Tipo C/uso terapêutico , Resultado do Tratamento
3.
J Proteome Res ; 15(12): 4709-4721, 2016 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-27748110

RESUMO

Connective tissues such as tendon, ligament and cartilage are mostly composed of extracellular matrix (ECM). These tissues are insoluble, mainly due to the highly cross-linked ECM proteins such as collagens. Difficulties obtaining suitable samples for mass spectrometric analysis render the application of modern proteomic technologies difficult. Complete solubilization of them would not only elucidate protein composition of normal tissues but also reveal pathophysiology of pathological tissues. Here we report complete solubilization of human Achilles tendon and yellow ligament, which is achieved by chemical digestion combined with successive protease treatment including elastase. The digestion mixture was subjected to liquid chromatography-mass spectrometry. The low specificity of elastase was overcome by accurate mass analysis achieved using FT-ICR-MS. In addition to the detailed proteome of both tissues, we also quantitatively determine the major protein composition of samples, by measuring peak area of some characteristic peptides detected in tissue samples and in purified proteins. As a result, differences between human Achilles tendon and yellow ligament were elucidated at molecular level.


Assuntos
Tendão do Calcâneo/química , Tecido Conjuntivo/química , Matriz Extracelular/química , Ligamentos/química , Proteoma/análise , Cromatografia Líquida , Humanos , Espectrometria de Massas , Peptídeo Hidrolases/metabolismo , Proteômica/métodos , Solubilidade
4.
J Med Genet ; 52(7): 476-83, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26032025

RESUMO

INTRODUCTION: Mesomelic dysplasias are a group of skeletal disorders characterised by shortness of the middle limb segments (mesomelia). They are divided into 11 different categories. Among those without known molecular basis is mesomelic dysplasia Savarirayan type, characterised by severe shortness of the middle segment of the lower limb. OBJECTIVE: To identify the molecular cause of mesomelic dysplasia Savarirayan type. METHODS AND RESULTS: We performed array comparative genomic hybridisation in three unrelated patients with mesomelic dysplasia Savarirayan type and identified 2 Mb overlapping de novo microdeletions on chromosome 6p22.3. The deletions encompass four known genes: MBOAT1, E2F3, CDKAL1 and SOX4. All patients showed mesomelia of the lower limbs with hypoplastic tibiae and fibulae. We identified a fourth patient with intellectual disability and an overlapping slightly larger do novo deletion also encompassing the flanking gene ID4. Given the fact that the fourth patient had no skeletal abnormalities and none of the genes in the deleted interval are known to be associated with abnormalities in skeletal development, other mutational mechanisms than loss of function of the deleted genes have to be considered. Analysis of the genomic region showed that the deletion removes two regulatory boundaries and brings several potential limb enhancers into close proximity of ID4. Thus, the deletion could result in the aberrant activation and misexpression of ID4 in the limb bud, thereby causing the mesomelic dysplasia. CONCLUSIONS: Our data indicate that the distinct deletion 6p22.3 is associated with mesomelic dysplasia Savarirayan type featuring hypoplastic, triangular-shaped tibiae and abnormally shaped or hypoplastic fibulae.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 6/genética , Fíbula/anormalidades , Proteínas Inibidoras de Diferenciação/metabolismo , Perna (Membro)/anormalidades , Osteocondrodisplasias/genética , Osteocondrodisplasias/patologia , Rádio (Anatomia)/anormalidades , Deleção de Sequência/genética , Tíbia/anormalidades , Ulna/anormalidades , Acetiltransferases/genética , Sequência de Bases , Hibridização Genômica Comparativa , Quinase 5 Dependente de Ciclina/genética , Fator de Transcrição E2F3/genética , Fíbula/patologia , Humanos , Proteínas Inibidoras de Diferenciação/genética , Proteínas de Membrana/genética , Dados de Sequência Molecular , Rádio (Anatomia)/patologia , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição SOXC , Análise de Sequência de DNA , Tíbia/patologia , Ulna/patologia , tRNA Metiltransferases
5.
Int Heart J ; 56(1): 105-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25742947

RESUMO

Urinary albumin excretion is a predictor of cardiovascular death. Cardiac rehabilitation (CR) with exercise training (ET) has been shown to improve exercise capacity and prognosis in patients with cardiovascular disease (CVD). However, it remains unclear whether CR reduces urinary albumin excretion in CVD patients. We performed a retrospective, observational study using data obtained from 98 male CVD patients without macroalbuminuria and estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m(2) who participated in CR with ET during hospitalization. Twenty-three patients continued supervised ET for 6 months (supervised group) and 75 patients quit supervised ET (non-supervised group). The supervised ET program consisted of 60 minutes of supervised sessions 1-3 times a week and 30-60 minutes of home exercise at least twice a week. Urinary albumin/creatinine ratio (ACR) was significantly decreased in the supervised group at 6 months after enrollment (43 ± 71 mg/g to 17 ± 20 mg/g creatinine, P < 0.05) but not in the non-supervised group. eGFR was unchanged in the supervised group but was significantly decreased in the non-supervised group (72 ± 18 mL/minute/1.73 m(2) to 67 ± 17 mL/minute/1.73 m(2), P < 0.001). The results of multiple regression analysis showed that only supervised ET was an independent contributor to ΔACR. CR with supervised ET decreased urinary albumin excretion without deterioration of renal function. These findings suggest that continuation of a supervised ET program is associated with reduction in the development of CVD and reduction in cardiovascular morbidity and mortality in CVD patients.


Assuntos
Albuminúria , Doenças Cardiovasculares , Terapia por Exercício , Organização e Administração , Idoso , Albuminas/análise , Albuminúria/diagnóstico , Albuminúria/etiologia , Albuminúria/metabolismo , Reabilitação Cardíaca , Doenças Cardiovasculares/complicações , Creatinina/sangue , Terapia por Exercício/métodos , Terapia por Exercício/organização & administração , Tolerância ao Exercício , Feminino , Taxa de Filtração Glomerular , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Resultado do Tratamento
6.
J Neuroeng Rehabil ; 10: 46, 2013 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-23687941

RESUMO

BACKGROUND: Spinal cord transection and peripheral nerve transection cause muscle atrophy and muscle fiber type conversion. It is still unknown how spinal cord transection and peripheral nerve transection each affect the differentiation of muscle fiber type conversion mechanism and muscle atrophy. The aim of our study was to evaluate the difference of muscle weight change, muscle fiber type conversion, and Peroxisome proliferator-activated receptor-γ coactivatior-1α (PGC-1α) expression brought about by spinal cord transection and by peripheral nerve transection. METHODS: Twenty-four Wistar rats underwent surgery, the control rats underwent a laminectomy; the spinal cord injury group underwent a spinal cord transection; the denervation group underwent a sciatic nerve transection. The rats were harvested of the soleus muscle and the TA muscle at 0 week, 1 week and 2 weeks after surgery. Histological examination was assessed using hematoxylin and eosin (H&E) staining and immunofluorescent staing. Western blot was performed with 3 groups. RESULTS: Both sciatic nerve transection and spinal cord transection caused muscle atrophy with the effect being more severe after sciatic nerve transection. Spinal cord transection caused a reduction in the expression of both sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection produced an increase in expression of sMHC protein and PGC-1α protein in the soleus muscle. The results of the expression of PGC-1α were expected in other words muscle atrophy after sciatic nerve transection is less than after spinal cord transection, however muscle atrophy after sciatic nerve transection was more severe than after spinal cord transection. CONCLUSION: In the conclusion, spinal cord transection diminished the expression of sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection enhanced the expression of sMHC protein and PGC-1α protein in the soleus muscle.


Assuntos
Fibras Musculares Esqueléticas/patologia , Atrofia Muscular/patologia , Traumatismos dos Nervos Periféricos/patologia , Traumatismos da Medula Espinal/patologia , Animais , Peso Corporal/fisiologia , Feminino , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/inervação , Músculo Esquelético/patologia , Atrofia Muscular/metabolismo , Tamanho do Órgão/fisiologia , Traumatismos dos Nervos Periféricos/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Ratos , Ratos Wistar , Nervo Isquiático/lesões , Traumatismos da Medula Espinal/metabolismo , Fatores de Transcrição/metabolismo
7.
Eur J Orthop Surg Traumatol ; 23(7): 791-5, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23412214

RESUMO

INTRODUCTION: Bone cyst formation in hips increases as osteoarthritis worsens. Although bone cysts in hips have been described in many studies, their etiology remains unclear and under debate. The purpose of this study was to investigate the communication between a bone cyst and the joint space, as well as the relationship between the severity of osteoarthritis and the formation of subchondral bone cysts in dysplastic hips. METHOD: We studied bone cysts from 150 dysplastic hips in 97 patients by computed tomography (CT) and plain radiography. We investigated the distribution of the bone cysts and the presence or absence of a communication path between the cysts and the joint space by three-dimensional (3D) CT. RESULT: Of the 150 hips, 94 acetabula and 55 femoral heads were found to contain cysts. Of the 94 hips containing acetabular cysts, 89 and 5 hips showed black lines and gray lines connecting the cyst and the joint space, respectively, on 3D-CT. The rate of cyst presentation in the hip increased as the joint space became narrower. The number of hips that possessed cysts in the anterior and/or middle portion was significantly higher than that in the posterior portions. CONCLUSION: Bone cysts in dysplastic osteoarthritic hips were found to communicate with the joint space in all cases. This suggests that the formation and enlargement of the cysts in dysplastic hips may be greatly influenced by the joint fluid. Cyst formation was initially observed in the anterior acetabulum, gradually progressing to involve the entire joint, including the posterior acetabulum and the femoral head, with worsening of the osteoarthritis.


Assuntos
Acetábulo/patologia , Cistos Ósseos/patologia , Cabeça do Fêmur/patologia , Luxação do Quadril/patologia , Osteoartrite do Quadril/patologia , Acetábulo/diagnóstico por imagem , Adolescente , Adulto , Idoso , Cistos Ósseos/diagnóstico por imagem , Feminino , Cabeça do Fêmur/diagnóstico por imagem , Luxação do Quadril/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto Jovem
8.
PLoS One ; 18(2): e0280634, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36795722

RESUMO

Chondromodulin (Cnmd) is a glycoprotein known to stimulate chondrocyte growth. We examined in this study the expression and functional role of Cnmd during distraction osteogenesis that is modulated by mechanical forces. The right tibiae of the mice were separated by osteotomy and subjected to slow progressive distraction using an external fixator. In situ hybridization and immunohistochemical analyses of the lengthened segment revealed that Cnmd mRNA and its protein in wild-type mice were localized in the cartilage callus, which was initially generated in the lag phase and was lengthened gradually during the distraction phase. In Cnmd null (Cnmd-/-) mice, less cartilage callus was observed, and the distraction gap was filled by fibrous tissues. Additionally, radiological and histological investigations demonstrated delayed bone consolidation and remodeling of the lengthened segment in Cnmd-/- mice. Eventually, Cnmd deficiency caused a one-week delay in the peak expression of VEGF, MMP2, and MMP9 genes and the subsequent angiogenesis and osteoclastogenesis. We conclude that Cnmd is necessary for cartilage callus distraction.


Assuntos
Calo Ósseo , Peptídeos e Proteínas de Sinalização Intercelular , Proteínas de Membrana , Osteogênese por Distração , Animais , Camundongos , Cartilagem , Fixadores Externos , Osteogênese/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteínas de Membrana/genética
9.
J Orthop Sci ; 17(4): 397-406, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22689132

RESUMO

BACKGROUND: During total hip arthroplasty (THA), the external iliac, femoral, and obturator vessels are at risk of vascular injury when penetrating the inner cortex of the pelvis. The purpose of this study was to clarify the location of these vessels using three-dimensional computed tomographic angiography (3DCT-A). METHODS: We enrolled 100 subjects (200 hips) without hip disease and performed examinations on the following. (1) External iliac-femoral vessels: we measured the shortest distance from these vessels to the pelvis on axial CT images and investigated the factors affecting distance. The anatomical course of the iliac artery was classified as straight, curved, or tortuous, and the correlation between course and age was established. (2) Obturator vessels: we measured the shortest distance from the obturator vessels to the quadrilateral surface on axial CT images. (3) Visualization of pelvic vessels was through the pelvis by dual-phase 3DCT-A. RESULTS: (1) The external iliac vein was located significantly closer to the pelvis than the artery, especially on the left side and in aged and female subjects. The single-curved and tortuous double-curved vessel types were found in aged subjects, and external iliac vessels of these types were closer to the pelvis than vessels of the straight type. In 36 subjects, the external iliac veins lay directly on the osseous surface of the pelvis (right 16, left 36). Of these 36 subjects, only one had straight-type vessels. (2) Obturator vessels were located just behind the acetabulum near the obturator foramen. (3) Reconstructed 3DCT images enabled us to visualize the pelvic vessels and demonstrated the danger area for penetrating the inner cortex of the pelvis. CONCLUSION: Understanding the anatomical orientation of the pelvic vessels around the acetabulum using 3DCT-A could be helpful for preventing vascular injury during THA.


Assuntos
Acetábulo/irrigação sanguínea , Acetábulo/diagnóstico por imagem , Angiografia/métodos , Artroplastia de Quadril , Imageamento Tridimensional , Pelve/irrigação sanguínea , Complicações Pós-Operatórias/prevenção & controle , Tomografia Computadorizada por Raios X/métodos , Doenças Vasculares/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Interpretação de Imagem Radiográfica Assistida por Computador
10.
J Orthop Traumatol ; 13(4): 225-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22815057

RESUMO

Bony defects in the spine are divided into three main types: spondylolysis, pediculolysis, and laminolysis. Lumbar spondylolysis is a well-known stress fracture that occurs frequently in adolescent athletes. Pediculolysis means stress fracture of the pedicle, which sometimes occurs subsequent to unilateral spondylolysis. Laminolysis is a rarely reported stress fracture similar to spondylolysis and pediculolysis that sometimes causes low back pain (LBP). However, its pathomechanism has not been elucidated. Recently, we encountered four adolescent athletes with symptomatic laminolysis. Mean age was 15.8 (range 15-17) years. All subjects reported severe LBP exacerbated by extension of the lumbar spine, and radiology revealed two types of laminolysis: hemilaminar type and intralaminar type. To elucidate the mechanisms of each type, we reviewed a biomechanical study, and found that the hemilaminar type was thought to be subsequent to contralateral spondylolysis, while the intralaminar type might be a result of a stress fracture due to repetitive extension loading.


Assuntos
Espondilólise/terapia , Adolescente , Fenômenos Biomecânicos , Fraturas de Estresse , Humanos , Dor Lombar/etiologia , Vértebras Lombares/lesões , Imageamento por Ressonância Magnética , Masculino , Pseudoartrose/complicações , Fraturas da Coluna Vertebral/complicações , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/fisiopatologia , Espondilólise/diagnóstico por imagem , Espondilólise/patologia , Espondilólise/fisiopatologia , Esportes , Tomografia Computadorizada por Raios X
11.
Skeletal Radiol ; 40(4): 467-73, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21107557

RESUMO

Low back pain (LBP) is the most prevalent musculoskeletal complaint among professional and amateur golfers; however, associated radiological changes in golf-related LBP have not been examined in the literature. We suspect that Modic Type 1 changes in the lumbar spine are linked to golf-related LBP. In this retrospective case series, four middle-aged golfers (one professional and three high-level amateurs) presented to our clinic with LBP. Inflammation of the right side of endplates in the lumbar spine was suspected based on Modic Type 1 changes detected by magnetic resonance imaging (MRI) in each patient. All four cases were diagnosed with right-sided endplate inflammation and administered intradiscal steroid injections with a non-steroidal anti-inflammatory drug (NSAID). Treatment swiftly alleviated LBP and diminished Modic Type 1 changes on follow-up MRI 3-6 months later in all four patients. We suggest that Modic Type 1 changes play a significant role in the diagnosis and treatment of golf-related LBP.


Assuntos
Golfe/lesões , Dor Lombar/etiologia , Vértebras Lombares/lesões , Humanos , Vértebras Lombares/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Radiografia
12.
Arch Orthop Trauma Surg ; 131(9): 1187-94, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21221610

RESUMO

AIM: Rounding surface of the sacral dome and wedging deformity of the vertebral body are commonly observed in patients with isthmic spondylolisthesis. Recently, an animal study showed that the deformity can be caused by the growth plate involvement in the immature pediatric vertebral body after biomechanical alteration due to the pars defects. However, the pathomechanism and biomechanics of these deformities have yet to be clarified. To demonstrate that the sacral rounding deformity observed in pediatric patients with spondylolisthesis can be reversed, and to understand the pathomechanism of the deformity from the biomechanical standpoint by analyzing changes of stress around the growth plate of the vertebral body due to spondylolysis. METHOD: Three-dimensional finite element pediatric lumbar models of the L3-L5 segment were utilized. Unlike the adult model, this pediatric model had growth plates and apophyseal rings. We analyzed stress distribution in response to 351°N axial compression and 10 N m moment in flexion, extension, lateral bending, and axial rotation. Bilateral spondylolysis was created in the model at the L4 level. The stress in the bilateral defect model was compared to the intact model predictions and the results obtained in the pediatric patients with sacral rounding deformity. RESULTS: Two patients presented rounding deformity of the anterior upper corner at S1 at the initial visit. They were asked to stop sports activities and use a soft trunk brace. Twelve months later, no rounding deformity was observed on the radiographs indicating that this deformity was reversible in pediatric cases. The biomechanical study indicated that in the pediatric spondylolytic spine, mechanical stress increased at the anterior upper corner during lumbar motion. CONCLUSION: In the presence of spondylolysis, mechanical stress increases in the growth plate at the anterior upper corner. Repetitive increases of mechanical stress may cause rounding deformity of the sacral dome mediated by growth plate involvement. When mechanical stress at the growth plate is reduced by wearing a brace, the proper functioning of the growth plate can help to remodel the sacral dome to its normal shape.


Assuntos
Vértebras Lombares/fisiopatologia , Espondilolistese/fisiopatologia , Fenômenos Biomecânicos , Braquetes , Criança , Feminino , Lâmina de Crescimento/fisiopatologia , Humanos , Vértebras Lombares/patologia , Masculino , Modelos Anatômicos , Espondilolistese/etiologia , Espondilolistese/patologia , Espondilolistese/terapia , Esportes , Estresse Mecânico
13.
J Pediatr Orthop B ; 30(5): 500-506, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32732799

RESUMO

Distraction osteogenesis is a widely used surgical technique to treat bone deformity and shortening. Several biological treatments have been studied to enhance bone formation during distraction osteogenesis in animals. However, role of osteoactivin in the osseous tissues during distraction osteogenesis remains poorly understood. In this animal experimental study, we investigated the spatiotemporal expression of osteoactivin by immunohistochemistry and real-time PCR using a mouse model for tibial lengthening. Furthermore, to address the role of osteoactivin in bone lengthening, we subjected the osteoactivin-transgenic mice to distraction osteogenesis model. During the lag phase, the fibroblast-like cells (possible progenitors of the osteoblasts or chondrocytes), which mainly express osteoactivin, were infiltrated into the osteotomy site. Osteoactivin was ubiquitously expressed in the lengthened segment during the distraction and consolidation phases. Consistent with the immunohistochemical analysis, the levels of the osteoactivin transcripts in the tibias were significantly increased throughout the distraction osteogenesis process. The bone mineral content in the osteoactivin-transgenic mice calculated using peripheral quantitative computed tomography was also significantly increased at the remodeling zone. The histomorphometric analysis revealed that newly formed callus resorption in the remodeling zone was significantly reduced but bone formation was not altered in the osteoactivin-transgenic mice. We conclude that osteoactivin functions as an inhibitor of callus resorption during the consolidation phase of distraction osteogenesis.


Assuntos
Reabsorção Óssea , Proteínas do Olho/genética , Glicoproteínas de Membrana/genética , Osteogênese por Distração , Animais , Osso e Ossos , Camundongos , Camundongos Transgênicos , Osteotomia , Tíbia
14.
Spine Surg Relat Res ; 5(1): 34-40, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33575493

RESUMO

INTRODUCTION: The specific morphology and differences between patients with cervical spondylotic myelopathy (CSM) and those with normal spines remain unclear. This study aimed to evaluate and determine the features of cervical spine morphology on reconstructive CT. METHODS: We investigated that axial reconstructive CT scans of the cervical spine at C3 to C7 were obtained from 309 individuals (97 CSM patients and 212 controls). Those of the optimal pedicle diameter were selected, and the following parameters were measured: (a) sagittal diameter of the spinal canal (b) transverse diameter of the spinal canal, (c) pedicle width, (d) lateral mass thickness, (e) transverse diameter of the foramen, (f) sagittal diameter of the vertebral body, and (g) transverse diameter of the vertebral body. The following ratios were calculated using these values: the sagittal-transverse ratio and the canal-body ratio. RESULTS: Most parameters differed significantly between the sexes in both groups. The parameters without the mean sagittal diameter of the spinal canal were significantly larger in men than in women. However, the mean sagittal diameter of the spinal canal did not differ significantly between the sexes in CSM patients. The sagittal-transverse ratio and canal-body ratio were significantly smaller in the CSM patients at all levels. According to relative operating characteristic curves of the sagittal diameter of the spinal canal, sagittal-transverse ratio, and canal-body ratio, the sensitivity from C3 to C7 in both sexes was > 60% at the threshold. In men, the specificity from C3 to C7 was also >60% at the threshold. CONCLUSIONS: The morphometry of the sagittal diameter of the spinal canal, sagittal-transverse ratio, and canal-body ratio on axial reconstructive CT images appears useful for distinguishing cervical spinal canal stenosis involving myelopathy.

15.
Skeletal Radiol ; 39(3): 299-304, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19960342

RESUMO

An ossified arachnoid membrane combined with cystic formation is rarely reported as a cause of spinal cord compression. We report the case of a 60-year-old man who presented with diffuse ossification of the arachnoid membrane (arachnoid ossification) and multiple cystic changes (arachnoid cyst) at the thoracic and lumbar spine. The lesions were surgically removed and progressive deterioration was prevented, although no marked improvement of neurological symptoms was attained.


Assuntos
Cistos Aracnóideos/complicações , Cistos Aracnóideos/diagnóstico , Ossificação Heterotópica/complicações , Ossificação Heterotópica/diagnóstico , Doenças da Medula Espinal/complicações , Doenças da Medula Espinal/diagnóstico , Aracnoide-Máter/diagnóstico por imagem , Aracnoide-Máter/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/patologia , Tomografia Computadorizada por Raios X
16.
Skeletal Radiol ; 39(3): 289-93, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19876627

RESUMO

Hematoma of the cervical ligamentum flavum is very rare, and its pathogenesis is unknown. We describe a case of ligamentum flavum hematoma in the cervical spine causing severe myelopathy. Postoperative histological examination suggested it was the result of the rupture of a hemangioma or of an arteriovenous malformation in the ligamentum flavum. After removal of the lesion, the patient's condition immediately improved. Review of all three reported cases, including this one, showed that complete resection of the mass resulted in immediate relief of symptoms of incomplete paraplegia. The findings of magnetic resonance imaging (MRI) of the hematoma may vary with time, and they may show no characteristic intensity. However, MRI of this case revealed that the tissues surrounding the mass were enhanced with gadolinium diethylene triamine penta-acetic acid, and an area of homogeneous iso-intensity was clearly surrounded by a low-intensity area (flavum) on T2-weighed short-tau inversion recovery images. These findings could be characteristic of the ligamentum flavum hematoma and might help in the differentiation from a cervical epidural hematoma.


Assuntos
Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/patologia , Hematoma/diagnóstico , Ligamento Amarelo/diagnóstico por imagem , Ligamento Amarelo/patologia , Doenças da Coluna Vertebral/diagnóstico , Idoso , Humanos , Masculino , Radiografia
17.
J Orthop Sci ; 15(3): 281-8, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20559793

RESUMO

BACKGROUND: Lumbar spondylolysis is a defect of the pars interarticularis known to occur as a stress fracture. Its incidence varies considerably depending on ethnicity, sex, and sports activity. However, there are few literature reviews describing its incidence in different ethnic groups or in people who engage in different sports. METHODS: We reviewed the most relevant articles on spondylolysis published in scientific journals. First, we focused on its incidence in various ethnic groups distributed by sex, the familial occurrence, and in patients with relevant diseases. Second, we focused on the incidence of spondylolysis in relation to the sports practiced by the patients. Although placing special emphasis on the incidence of lumbar spondylolysis in the general population in Japan, we also reviewed the Japanese and English literature to investigate its incidence among those who engage in different sports. RESULTS: The incidence of lumbar spondylolysis in the general Japanese population was 5.9%. Most studies report that the incidence in higher in male subjects than in female subjects. We found that Japanese rugby and judo players were prone to suffer lumbar spondylolysis, at an incidence of about 20%. However, the incidence for Japanese professional soccer and baseball players was much higher, at 30%, which was more than five times the incidence in the general Japanese population. CONCLUSIONS: The incidence of lumbar spondylolysis varies depending on ethnicity, sex, family history, relevant disease, and sports activity.


Assuntos
Fraturas de Estresse/epidemiologia , Vértebras Lombares/lesões , Espondilólise/epidemiologia , Negro ou Afro-Americano , Traumatismos em Atletas/epidemiologia , Feminino , Fraturas de Estresse/etnologia , Humanos , Incidência , Japão/epidemiologia , Masculino , Espondilólise/etnologia , Estados Unidos/epidemiologia , População Branca
18.
J Orthop Traumatol ; 11(3): 183-7, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20669040

RESUMO

We report a rare case of congenital absence of the L5-S1 facet joint, which was associated with a conjoined nerve root. Combination of these two anomalies has been quite rarely reported in the literature. A 39-year-old man presented with acute low back pain and right leg radiating pain. Muscle weakness and sensory disturbance of the right leg were also apparent in the region innervated by L5 and S1 nerve roots. Preoperative multidetector three-dimensional computed tomography (3D-CT) showed complete absence of the right S1 superior articular process. Magnetic resonance (MR) images showed lumbar disc herniation at right L5-S1 level that migrated cranially. Intraoperative findings revealed that the right L5 nerve root and S1 nerve root were conjoined, and the conjoined nerve root was compressed by L5-S1 disc herniation, which led to impairment of the conjoined nerve root by a single-level lumbar disc herniation. After removal of the disc herniation, his right leg pain immediately subsided, however muscle weakness and sensory disturbance persisted. Surgeons should be aware of this nerve root anomaly when examining a patient who shows an unusual clinical presentation and/or congenital osseous anomaly.


Assuntos
Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/fisiopatologia , Plexo Lombossacral/anormalidades , Articulação Zigapofisária/anormalidades , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/cirurgia , Adulto , Descompressão Cirúrgica/métodos , Seguimentos , Humanos , Imageamento Tridimensional/métodos , Deslocamento do Disco Intervertebral/diagnóstico , Dor Lombar/diagnóstico , Dor Lombar/etiologia , Vértebras Lombares/cirurgia , Região Lombossacral , Imageamento por Ressonância Magnética/métodos , Masculino , Doenças Raras , Medição de Risco , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Articulação Zigapofisária/cirurgia
19.
J Orthop Traumatol ; 11(3): 189-93, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20721597

RESUMO

Retroisthmic cleft refers to a cleft in the lamina and is rarely reported. It was first described by Brocher, and later Wick et al. proposed the term "laminolysis" to describe the retroisthmic cleft by analogy with the nomenclature of the applied stress fracture of the pars interarticularis (spondylolysis) and the pedicle (pediculolysis). In this paper, we describe two adolescent sports players with symptomatic lumbar laminolysis. Both improved significantly after adequate conservative treatment. Knowledge of laminolysis in adolescent patients with low back pain is necessary to avoid overlooking it and late diagnosis. For correct diagnosis, multidetector three-dimensional computed tomography (CT) is suggested. In addition, magnetic resonance imaging (MRI) also allows detection of inflammation in the defects.


Assuntos
Interpretação de Imagem Assistida por Computador , Vértebras Lombares , Imageamento por Ressonância Magnética/métodos , Espondilólise/diagnóstico , Espondilólise/terapia , Adolescente , Seguimentos , Humanos , Imobilização/métodos , Injeções Intra-Articulares/métodos , Lidocaína/uso terapêutico , Dor Lombar/diagnóstico , Dor Lombar/etiologia , Masculino , Medição da Dor , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Espondilólise/complicações , Esteroides/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
20.
J Orthop Traumatol ; 11(4): 257-61, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21103903

RESUMO

Erosion of spinal osseous structure, so-called scalloping, has been rarely reported associated with herniated nucleus pulposus (HNP). We report a rare case of HNP causing erosion of the spinal osseous structure (including lamina). The patient was an 81-year-old woman with 3-year history of low-back pain and left leg radiating pain. Muscle weakness of the left leg was also apparent. Computed tomography following myelography showed severe compression of the dural sac at the level of L3-L4; furthermore, erosion of the lamina, pedicle, and vertebral body was noted, indicating that the space-occupying mass was most probably a tumorous lesion. The mass also showed calcification inside. During the surgery, the mass was confirmed to be an HNP with calcification. Following resection, the pain disappeared. Surgeons should be aware of the possibility of scalloping of the vertebrae caused by HNP mimicking a tumorous lesion.


Assuntos
Compressão da Medula Espinal/diagnóstico , Compressão da Medula Espinal/etiologia , Medula Espinal , Neoplasias da Coluna Vertebral/diagnóstico , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Vértebras Lombares
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