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1.
J Orthop Res ; 42(4): 855-863, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37971281

RESUMO

There is a clinical need for alternatives to gadolinium contrast-enhanced magnetic resonance imaging (MRI) to facilitate early detection and assessment of femoral head ischemia in pediatric patients with Legg-Calvé-Perthes disease (LCPD), a juvenile form of idiopathic osteonecrosis of the femoral head. The purpose of this study was to determine if intravoxel incoherent motion (IVIM), a noncontrast-enhanced MRI method to simultaneously measure tissue perfusion and diffusion, can detect femoral head ischemia using a piglet model of LCPD. Twelve 6-week-old piglets underwent unilateral hip surgery to induce complete femoral head ischemia. The unoperated, contralateral femoral head served as a perfused control. The bilateral hips of the piglets were imaged in vivo at 3T MRI using IVIM and contrast-enhanced MRI 1 week after surgery. Median apparent diffusion coefficient (ADC) and IVIM parameters (diffusion coefficient: Ds; perfusion coefficient: Df; perfusion fraction: f; and perfusion flux: f*Df) were compared between regions of interest comprising the epiphyseal bone marrow of the ischemic and control femoral heads. Contrast-enhanced MRI confirmed complete femoral head ischemia in 11/12 piglets. IVIM perfusion fraction (f) and flux (f*Df) were significantly decreased in the ischemic versus control femoral heads: on average, f decreased 47 ± 27% (Δf = -0.055 ± 0.034; p = 0.0003) and f*Df decreased 50 ± 27% (Δf*Df = -0.59 ± 0.49 × 10-3 mm2/s; p = 0.0026). In contrast, IVIM diffusion coefficient (Ds) and ADC were significantly increased in the ischemic versus control femoral heads: on average, Ds increased 78 ± 21% (ΔDs = 0.60 ± 0.14 × 10-3 mm2/s; p < 0.0001) and ADC increased 60 ± 36% (ΔADC = 0.50 ± 0.23 × 10-3 mm2/s; p < 0.0001). In conclusion, IVIM is sensitive in detecting bone marrow ischemia in a piglet model of LCPD.


Assuntos
Cabeça do Fêmur , Doença de Legg-Calve-Perthes , Humanos , Animais , Criança , Suínos , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/patologia , Doença de Legg-Calve-Perthes/diagnóstico por imagem , Doença de Legg-Calve-Perthes/patologia , Meios de Contraste , Imageamento por Ressonância Magnética , Isquemia/diagnóstico por imagem , Movimento (Física)
2.
Cytokine ; 168: 156233, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37247447

RESUMO

OBJECTIVE: Legg-Calvé-Perthes disease (LCPD) is a partial or total necrosis of femoral head bone caused by blood supply disorder and its etiology is not clear. Studies have revealed that microRNA-214-3p (miR-214-3p) plays a vital role in LCPD, however, its exact mechanism is still unclear. In this study, we investigated the potential role of chondrocytes-derived exosomes carrying miR-214-3p (exos-miR-214-3p) in the pathogenesis of LCPD. METHODS: RT-qPCR was performed to evaluate miR-214-3p expression level in femoral head cartilage, serum and chondrocytes of patients with LCPD, as well as dexamethasone (DEX)-exposed TC28 cells. Effects of exos-miR-214-3p on the proliferation and apoptosis were verified via MTT assay, TUNEL staining and caspase3 activity assay. The M2 macrophage markers were assessed by flow cytometry, RT-qPCR and Western blot. Moreover, angiogenic effects of human umbilical vein endothelial cells (HUVECs) were tested using CCK-8 and tube formation assays. Bioinformatics prediction, luciferase assay and ChIP were applied to verify the association between ATF7, RUNX1 and miR-214-3p. RESULTS: miR-214-3p was found to be decreased in patients with LCPD and DEX-treated TC28 cells, of which overexpression promoted cell proliferation and suppressed apoptosis. Mechanistically, exos-miR-214-3p facilitated M2 polarization by ATF7/TLR4 axis and HUVECs angiogenesis via RUNX1/VEGFA axis. CONCLUSION: miR-214-3p alleviates LCPD by promoting M2 polarization of macrophages and angiogenesis.


Assuntos
Exossomos , Doença de Legg-Calve-Perthes , MicroRNAs , Humanos , Condrócitos/metabolismo , Doença de Legg-Calve-Perthes/genética , Doença de Legg-Calve-Perthes/metabolismo , Doença de Legg-Calve-Perthes/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Exossomos/genética , Exossomos/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Macrófagos/metabolismo
3.
Tissue Eng Regen Med ; 20(3): 489-501, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37041432

RESUMO

BACKGROUND: Legg-Calvé-Perthes disease (LCPD) is still a refractory disease in children's orthopedics. With the introduction of the concept of "osteoimmunology", the immune-inflammatory mechanisms between bone and immune system have become a research focus of LCPD. However, few studies have reported on the pathological role of inflammation-related receptors such as toll-like receptors (TLRs) as well as immune cells such as macrophages in LCPD. This study was for investigating the mechanism of TLR4 signaling pathway on the direction of macrophage polarization and the repair of avascular necrosis of femoral epiphysis in LCPD. METHODS: With GSE57614 and GSE74089, differentially expressed genes were screened. Through enrichment analysis and protein-protein interaction network, the functions of TLR4 were explored. Furthermore, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), hematoxylin & eosin (H&E) staining, micro-CT, tartrate-resistant acid phosphatase (TRAP) dyeing and western blotting were performed for determining the influences of TAK-242 (a TLR4 inhibitor) on the repair of avascular necrosis of femoral epiphysis in rat models. RESULTS: Totally 40 co-expression genes were screened as well as enriched in TLR4 signaling pathway. Immunohistochemistry and ELISA analyses certified that TLR4 facilitated macrophage polarization toward the M1 phenotype and prevented macrophage polarization toward the M2 phenotype. Besides, the results of H&E and TRAP staining, micro-CT, and western blotting showed that TAK-242 can inhibit osteoclastogenesis and promote osteogenesis. CONCLUSION: Inhibition of TLR4 signaling pathway accelerated the repair of avascular necrosis of femoral epiphysis by regulating macrophage polarization in LCPD.


Assuntos
Doença de Legg-Calve-Perthes , Animais , Ratos , Doença de Legg-Calve-Perthes/genética , Doença de Legg-Calve-Perthes/patologia , Receptor 4 Toll-Like/genética , Epífises/patologia , Transdução de Sinais , Macrófagos , Necrose
4.
J Orthop Res ; 40(2): 484-494, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33788301

RESUMO

This study investigated the sensitivity of T1ρ and T2 relaxation time mapping to detect acute ischemic injury to the secondary ossification center (SOC) and epiphyseal cartilage of the femoral head in a piglet model of Legg-Calvé-Perthes disease. Six piglets underwent surgery to induce global right femoral head ischemia and were euthanized 48 h later. Fresh operated and contralateral-control femoral heads were imaged ex vivo with T1, T2, and T1ρ mapping using a 9.4T magnetic resonance imaging scanner. The specimens were imaged a second time after a freeze/thaw cycle and then processed for histology. T1, T2, and T1ρ measurements in the SOC, epiphyseal cartilage, articular cartilage, and metaphysis were compared between operated and control femoral heads using paired t tests. The effects of freeze/thaw, T1ρ spin-lock frequency, and fat saturation were also investigated. Five piglets with histologically confirmed ischemic injury were quantitatively analyzed. T1ρ was increased in the SOC (101 ± 15 vs. 73 ± 16 ms; p = 0.0026) and epiphyseal cartilage (84.9 ± 9.2 vs. 74.3 ± 3.6 ms; p = 0.031) of the operated versus control femoral heads. T2 was also increased in the SOC (28.7 ± 2.0 vs. 22.7 ± 1.7; p = 0.0037) and epiphyseal cartilage (57.4 ± 4.7 vs. 49.0 ± 2.7; p = 0.0041). No changes in T1 were detected. The sensitivities of T1ρ and T2 mapping in detecting ischemic injury were maintained after a freeze/thaw cycle, and T1ρ sensitivity was maintained after varying spin-lock frequency and applying fat saturation. In conclusion, T1ρ and T2 mapping are sensitive in detecting ischemic injury to the SOC and epiphyseal cartilage of the femoral head as early as 48 h after ischemia induction.


Assuntos
Cartilagem Articular , Doença de Legg-Calve-Perthes , Animais , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/patologia , Lâmina de Crescimento/patologia , Isquemia/diagnóstico por imagem , Isquemia/etiologia , Doença de Legg-Calve-Perthes/diagnóstico por imagem , Doença de Legg-Calve-Perthes/patologia , Imageamento por Ressonância Magnética/métodos , Suínos
5.
Sci Rep ; 11(1): 16506, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34389771

RESUMO

The acetabular retroversion has a moderate incidence of 31-60% in all patients of the Perthes disease. It might be caused by posterior wall dysplasia based on recent animal researches. However, some studies support that hemipelvic retroversion is the main factor for the acetabular retroversion. The primary pathological factor of increasing retroversion angle is still controversial anatomically. This study aimed to identify whether there is acetabular retroversion in children with Perthes disease,and to find a method to distinguish version types. Forty children with unilateral Perthes disease who were admitted to our hospital from January 1, 2012 to December 31, 2018 were enrolled, and 40 controls were matched based on sex and age. The acetabular anteversion angle (AAA), internal wall anteversion angle (IWAA), anterior wall height of the acetabulum (A), acetabular posterior wall height (P), and acetabular width (W) were assessed on computed tomography (CT) at the level of the femoral head center. The acetabular wall difference index (AWDI; AWDI = P-A)/W*100) was calculated. The mean AAA was significantly lower in Perthes disease hips (10.59 (8.05-12.46)) than in contralateral hips (12.04 (9.02-13.33)) (p = 0.002) but did not differ from control hips (9.68 ± 3.76) (p = 0.465). The mean IWAA was significantly lower in Perthes hips (9.16 ± 3.89) than in contralateral hips (11.31 ± 4.04) (p = 0.000) but did not differ from control hips (9.43 ± 3.82) (p = 0.753). The mean AWDI did not differ between Perthes hips (0.41 ± 4.94) and contralateral hips (- 1.12 (- 4.50, 2.17)) (p = 0.06) or control hips (- 0.49 ± 5.46) (p = 0.437). The mean W was significantly higher in Perthes hips (44.61 ± 5.06) than in contralateral hips (43.36 ± 4.38) (p = 0.000) but did not differ from control hips (45.02 ± 5.01) (p = 0.719). The mean A and P did not differ between Perthes hips and contralateral hips or control hips. Correlation analysis of all hip joints revealed a significant correlation between AAAs and IWAAs (r = 0.772; r = 0.643; r = 0.608; and r = 0.540). Linear regression analysis revealed that AAAs increased with IWAAs. Multiple linear regression showed that IWAAs and AWDIs have good predictive value for AAAs in both Perthes and control hips (R2 = 0.842, R2 = 0.869). In patients with unilateral Perthes disease, the affected acetabulum is more retroverted than that on the contralateral side, which may be caused by hemipelvic retroversion. The measurements in this study could distinguish the form of acetabular retroversion. IWAAs and AWDIs can be used as new observations in future studies of acetabular version.


Assuntos
Acetábulo/patologia , Doença de Legg-Calve-Perthes/patologia , Ossos Pélvicos/patologia , Pelve/patologia , Acetábulo/diagnóstico por imagem , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Ossos Pélvicos/diagnóstico por imagem , Pelve/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
6.
J Pediatr Orthop ; 41(6): 344-351, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33843788

RESUMO

BACKGROUND: Early containment surgery has become increasingly popular in Legg-Calvé-Perthes Disease (LCPD), especially for older children. These procedures treat the proximal femur, the acetabulum, or both, and most surgeons endorse the same surgical option regardless of an individual patient's anatomy. This "one-surgery-fits-all" approach fails to consider potential variations in baseline anatomy that may make one option more sensible than another. We sought to describe hip morphology in a large series of children with newly diagnosed LCPD, hypothesizing that variation in anatomy may support the concept of anatomic-specific containment. METHODS: A retrospective review of a prospectively collected multicenter database was conducted for patients aged 6 to 11 at diagnosis. To assess anatomy before significant morphologic changes secondary to the disease itself, only patients in Waldenström stages IA/IB were included. Standard hip radiographic measurements including acetabular index, lateral center-edge angle, proximal femoral neck-shaft angle (NSA), articulotrochanteric quartiles, and extrusion index (EI) were made on printed anteroposterior pelvis radiographs. Age-specific percentiles were calculated for these measures using published norms. Significant outliers (≤10th/≥90th percentile) were reported where applicable. RESULTS: A total of 168 patients with mean age at diagnosis of 8.0±1.3 years met inclusion criteria (81.5% male). Mean acetabular index for the entire cohort was 16.8±4.1 degrees; 58 hips (34.5%) were significantly dysplastic compared with normative data. Mean lateral center-edge angle was 15.9±5.2 degrees at diagnosis; 110 (65.5%) were ≤10th percentile indicating dysplasia (by this metric). Mean NSA overall was 136.5±7.0 degrees. Fifty-one (30.4%) and 20 (11.9%) hips were significantly varus (≤10th percentile) or valgus (≥90th percentile), respectively. Thirty-five hips (20.8%) were the third articulo-trochanteric quartiles or higher suggesting a higher-riding trochanter at baseline. Mean EI was 15.5%±9.0%, while 63 patients (37.5%) had an EI ≥20%. CONCLUSIONS: The present study finds significant variation in baseline anatomy in children with early-stage LCPD, including a high prevalence of coexisting acetabular dysplasia as well as high/low NSAs. These variations suggest that the "one-surgery-fits-all" approach may lack specificity for a particular patient; a potentially wiser option may be an anatomic-specific containment operation (eg, acetabular-sided osteotomy for coexisting dysplasia, varus femoral osteotomy for valgus NSA). LEVEL OF EVIDENCE: Level IV.


Assuntos
Acetábulo/patologia , Cabeça do Fêmur/patologia , Doença de Legg-Calve-Perthes/patologia , Doença de Legg-Calve-Perthes/cirurgia , Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Variação Anatômica , Criança , Bases de Dados Factuais , Epífises/diagnóstico por imagem , Epífises/patologia , Epífises/cirurgia , Feminino , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/cirurgia , Luxação do Quadril/complicações , Luxação do Quadril/diagnóstico por imagem , Luxação do Quadril/cirurgia , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/patologia , Articulação do Quadril/cirurgia , Humanos , Doença de Legg-Calve-Perthes/complicações , Doença de Legg-Calve-Perthes/diagnóstico por imagem , Masculino , Radiografia , Estudos Retrospectivos
7.
J Pediatr Orthop ; 40(4): 168-175, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32132446

RESUMO

BACKGROUND: Two operative procedures are currently advocated to stimulate the necrotic femoral head healing in children with Legg-Calve-Perthes disease: transphyseal neck-head tunneling (TNHT) and multiple epiphyseal drilling (MED). The purpose of this study was to compare the bone healing and physeal function after treatment with TNHT or MED in a piglet model of ischemic osteonecrosis. METHODS: Eighteen piglets were induced with osteonecrosis by surgically placing a ligature tightly around the right femoral neck. One week later, the piglets were assigned to 1 of 3 treatment groups (n=6/group): (1) local nonweight bearing only (NWB), (2) TNHT plus NWB, or (3) MED plus NWB. The unoperated left femoral heads were used as normal controls. The animals were euthanized at 8 weeks after osteonecrosis induction. Histologic, histomorphometric, radiographic, microcomputed tomography (CT), and calcein-labeling assessments were performed. Statistical analysis included a 1-way ANOVA. RESULTS: Micro-CT analyses showed higher femoral head bone volume in the MED group compared with the TNHT and the NWB groups (P<0.01). The MED group had a higher mean trabecular number (P<0.001) and new bone formation (P=0.001) based on calcein-labeling parameters compared with the TNHT and the NWB groups. In addition, the osteoclast number per bone surface was lower in the MED group compared with the NWB group (P=0.001). Histologic and micro-CT assessments of the proximal femoral physis revealed a larger physeal disruption at the site of physeal drilling in the TNHT group compared with the MED group. However, no significant differences in physeal elongation (P=0.61) and femoral neck length (P=0.31) were observed between the treatment groups. CONCLUSIONS: MED produced a higher bone volume and stimulated greater bone formation than the TNHT or the NWB alone. Both procedures did not produce a significant physeal growth disturbance during the study period. CLINICAL RELEVANCE: This preclinical study provides evidence that MED produces more favorable bone healing than the TNHT in a large animal model of Legg-Calve-Perthes disease.


Assuntos
Cabeça do Fêmur , Doença de Legg-Calve-Perthes , Procedimentos Ortopédicos/métodos , Osteonecrose , Animais , Modelos Animais de Doenças , Epífises/patologia , Epífises/cirurgia , Cabeça do Fêmur/irrigação sanguínea , Cabeça do Fêmur/patologia , Cabeça do Fêmur/cirurgia , Necrose da Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/cirurgia , Lâmina de Crescimento/patologia , Lâmina de Crescimento/cirurgia , Humanos , Doença de Legg-Calve-Perthes/patologia , Doença de Legg-Calve-Perthes/cirurgia , Osteonecrose/diagnóstico , Osteonecrose/etiologia , Osteonecrose/cirurgia , Suínos , Resultado do Tratamento , Cicatrização , Microtomografia por Raio-X/métodos
8.
Mol Med Rep ; 20(1): 685-692, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180556

RESUMO

Legg­Calvé­Perthes disease (LCPD) is a pediatric form of femoral head osteonecrosis with unknown etiology. MicroRNAs (miRs) have been revealed to serve an important role in LCPD. MiR­214 serves an important role in chondrogenesis. The aim of the present study was to investigate the potential role of miR­214 in LCPD and the underlying mechanisms. The expression levels of miR­214 and B­cell lymphoma 2 (Bcl­2)­associated X protein (Bax) in dexamethasone (DEX)­treated TC28 cells, and the femoral head cartilage tissues, serum and primary chondrocytes of patients with LCPD, and healthy individuals were determined via reverse transcription quantitative polymerase chain reaction and western blot analysis. A luciferase reporter assay was conducted to investigate the association between miR­214 and Bax, while cell viability was determined via an MTT assay, and flow cytometry was performed to investigate cell apoptosis. The results revealed that miR­214 was downregulated and Bax was upregulated in DEX­treated TC28 cells and tissues obtained from patients with LCPD. MiR­214 was demonstrated to directly target Bax and negatively regulate its expression. DEX administration significantly suppressed cell proliferation, promoted apoptosis and decreased the Bcl­2/Bax ratio in TC28 cells; overexpression of miR­214 induced opposing effects, which were reversed by Bax overexpression. In conclusion, the results indicated that miR­214 and Bax may be potential therapeutic targets for the future clinical treatment of LCPD.


Assuntos
Doença de Legg-Calve-Perthes/genética , MicroRNAs/genética , Adolescente , Apoptose , Cartilagem/metabolismo , Cartilagem/patologia , Células Cultivadas , Criança , Condrócitos/metabolismo , Condrócitos/patologia , Regulação para Baixo , Feminino , Regulação da Expressão Gênica , Humanos , Doença de Legg-Calve-Perthes/sangue , Doença de Legg-Calve-Perthes/patologia , Masculino , MicroRNAs/sangue , Proteína X Associada a bcl-2/genética
9.
J Am Acad Orthop Surg ; 26(15): 515-525, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29939866

RESUMO

Hip osteoarthritis (OA) exerts a significant burden on society, affecting 3% of Americans aged >30 years. Recent advances in the understanding of the pathoanatomy and pathomechanics of the hip have led to treatment options for young adults with hip pain. Femoroacetabular impingement, specifically cam-type femoroacetabular impingement, hip dysplasia, and the sequelae of pediatric hip disease can predispose the hip to early OA. However, many patients with abnormal anatomic findings do not develop early OA, suggesting that there exist other patient characteristics that are protective despite abnormal bony anatomy. Outcome studies show that arthroscopic and open hip procedures improve pain and function in patients with symptomatic hips. However, there is currently limited evidence that these procedures extend the life of the patient's natural hip. Additional studies are needed to determine protective or adaptive factors in patients with abnormal anatomy who do not develop early OA and to determine whether joint preserving hip surgery extends the life of the native hip joint.


Assuntos
Acetábulo/anormalidades , Impacto Femoroacetabular/patologia , Luxação do Quadril/patologia , Articulação do Quadril/anormalidades , Doença de Legg-Calve-Perthes/patologia , Osteoartrite do Quadril/epidemiologia , Osteoartrite do Quadril/etiologia , Impacto Femoroacetabular/complicações , Impacto Femoroacetabular/diagnóstico por imagem , Impacto Femoroacetabular/cirurgia , Luxação do Quadril/complicações , Luxação do Quadril/cirurgia , Articulação do Quadril/patologia , Articulação do Quadril/cirurgia , Humanos , Incidência , Doença de Legg-Calve-Perthes/complicações , Doença de Legg-Calve-Perthes/cirurgia , Prevalência , Suporte de Carga
10.
J Orthop Res ; 35(9): 2051-2058, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-27864891

RESUMO

The purpose of this study was to quantify femoral head deformity in patients with Legg-Calvé-Perthes disease (LCPD) using a novel three dimensional (3D) magnetic resonance imaging (MRI) reconstruction and volume based analysis. Bilateral femoral heads of 17 patients (mean age 9.9 ± 2.0 years; 12 boys, 5 girls) with LCPD were scanned 1-2 times (n = 33 LCPD heads, 20 normal heads) using a 1.5T MRI scanner. Fourteen patients had unilateral and three had bilateral LCPD with five hips in the Waldenström initial stage, 9 in the fragmentation stage, 14 in the reossification stage, and 5 in the healed stage. 3D digital reconstructions of femoral heads were created using MIMICS software. Deformity was quantified using a 3D volume ratio method based on reference hemisphere volume as well as two surface geometry methods. Intra-observer analysis showed that 97% of the LCPD femoral heads were within 10% of the original value and test shapes had 99.6% accuracy. For normal femoral heads, the volume ratios of all except one were between 95 and 98% (n = 20) of a perfect hemisphere volume. For femoral heads affected with LCPD, the volume ratios ranged from 43% to 96% of a perfect hemisphere (n = 33). The volume ratio method and the two surface geometry comparison methods had high correlation (r = 0.89 and 0.96). In summary, the 3D MRI volume ratio method allowed accurate quantification and demonstrated small changes (<10%) of the femoral head deformity in LCPD. This method may serve as a useful tool to evaluate the effects of treatment on femoral head shape. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2051-2058, 2017.


Assuntos
Coxa Magna/diagnóstico por imagem , Cabeça do Fêmur/diagnóstico por imagem , Doença de Legg-Calve-Perthes/diagnóstico por imagem , Criança , Coxa Magna/etiologia , Feminino , Cabeça do Fêmur/patologia , Humanos , Imageamento Tridimensional , Doença de Legg-Calve-Perthes/complicações , Doença de Legg-Calve-Perthes/patologia , Imageamento por Ressonância Magnética , Masculino
11.
Homo ; 68(1): 10-17, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27940070

RESUMO

Legg-Calvé-Perthes is a very rare disease involving childhood osteochondrosis of the femoral head due to interruption of its blood supply. The etiology is unknown. The signs of the pathology are well described in the literature but few paleopathological cases have been reported, mostly dating from Late Antiquity to Early Middle Ages. Here we report on morphometric and radiological analyses of a skeleton from the Etruscan necropolis of Spina (Ferrara, Italy, 6th-3rd century BCE), to our knowledge the most ancient case of Legg-Calvé-Perthes disease published thus far.


Assuntos
Doença de Legg-Calve-Perthes/história , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/patologia , História Antiga , Humanos , Itália , Doença de Legg-Calve-Perthes/diagnóstico por imagem , Doença de Legg-Calve-Perthes/patologia , Paleopatologia , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/patologia , Tomografia Computadorizada por Raios X
12.
Am J Pathol ; 186(11): 2987-2999, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27648614

RESUMO

In Legg-Calvé-Perthes disease, loss of blood supply results in ischemic osteonecrosis of the femoral head (ONFH). Generally, macrophages play important roles in inflammatory responses to tissue necrosis, but their role in ONFH is not known. The purpose of this study was to determine the macrophage-inflammatory responses after ONFH and the receptor mechanisms involved in sensing the necrotic bone, using a piglet model of Legg-Calvé-Perthes disease. Induction of ONFH resulted in increased numbers of CD14+ macrophages in the fibrovascular repair tissue compared with normal, as determined by immunohistochemistry. Quantitative real-time PCR analysis of macrophages isolated by laser capture microdissection showed significantly increased expression of proinflammatory cytokines IL-1ß, tumor necrosis factor-α, and IL-6 in ONFH compared with normal. Because Toll-like receptors (TLRs) mediate macrophage-inflammatory responses in other inflammatory conditions, we determined their gene expression in macrophages and found significantly increased levels of TLR4 but not TLR2 and TLR9 in ONFH. Mechanistically, in vitro, bone marrow-derived macrophages treated with necrotic bone showed increased extracellular signal-regulated kinases 1/2 and Iκ kinase-α phosphorylation, increased proliferation, migration, and inflammatory cytokine expression, which were blocked by TLR4 inhibitor, TAK242, and by TLR4 ablation in macrophages using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease method. In conclusion, necrotic bone stimulates macrophage-inflammatory responses through TLR4 activation.


Assuntos
Necrose da Cabeça do Fêmur/imunologia , Doença de Legg-Calve-Perthes/imunologia , Macrófagos/imunologia , Receptor 4 Toll-Like/imunologia , Animais , Medula Óssea/imunologia , Medula Óssea/patologia , Proliferação de Células , Citocinas/metabolismo , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Necrose da Cabeça do Fêmur/patologia , Inflamação/imunologia , Inflamação/patologia , Doença de Legg-Calve-Perthes/patologia , Suínos , Receptor 2 Toll-Like/metabolismo , Receptores Toll-Like/metabolismo
13.
Pediatr Ann ; 45(4): e144-9, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27064472

RESUMO

Legg-Calve-Perthes disease (LCPD) is the insidious onset of idiopathic avascular necrosis of the hip in the pediatric population. The disease encompasses a wide spectrum of pathology, from mild with no long-term sequelae to severe with permanent degenerative change of the hip joint. A pediatric patient with hip pathology may initially only present with knee or thigh pain, thus obligating the clinician to maintain awareness about the hip during examination. Common physical examination findings include deficits in hip abduction and internal rotation, along with Trendelenburg gait in late stages. Plain radiographs demonstrate changes in the anterolateral aspect of the femoral head, sometimes only seen on the frog lateral X-ray in early stages. Treatment options aim to restore range of motion and maintain adequate coverage of the femoral head. When appropriate, surgery is used to reorient the femoral head or pelvis to maintain coverage.


Assuntos
Doença de Legg-Calve-Perthes/diagnóstico por imagem , Criança , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/patologia , Humanos , Doença de Legg-Calve-Perthes/complicações , Doença de Legg-Calve-Perthes/patologia , Masculino , Dor/etiologia
14.
Medicine (Baltimore) ; 94(49): e2221, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26656361

RESUMO

Children obesity has become one of the most important public health problems in many countries worldwide. Although the awareness of childhood obesity as a modifiable health risk is high, but many societies do not prioritize this issue as a health care problem, which may lead to comorbidities and even premature death. Despite the rising interest in bariatric surgery for children, only laparoscopic sleeve gastrectomy (LSG) is being considered in resolving childhood obesity who failed other dietary or drug therapies; however many of LSG procedures failed to reduce the weight in children or resulted in complications postsurgery.Here, we present a novel bariatric procedure to clue out a female child 13 years old presented with Legg-Calvé-Perthes disease-associated morbid obesity. The surgical bariatric technique applied both fundal resection and surgical bypass in pediatric obesity using the Elbanna novel bariatric technique.Bariatric surgical bypass may be considered in complicated-childhood cases who failed all other options.


Assuntos
Cirurgia Bariátrica/métodos , Obesidade Mórbida/cirurgia , Obesidade Infantil/cirurgia , Adolescente , Feminino , Humanos , Doença de Legg-Calve-Perthes/etiologia , Doença de Legg-Calve-Perthes/patologia , Obesidade Mórbida/complicações , Obesidade Infantil/complicações
15.
Ugeskr Laeger ; 177(2A): 68-9, 2015 Jan 26.
Artigo em Dinamarquês | MEDLINE | ID: mdl-25612973

RESUMO

Buschke-Ollendorff syndrome is a rare condition characterized by skin manifestations and osteopoikilosis. We describe a mother and her son who presented with indurated skin lesions suggestive of connective tissue naevi. X-rays showed multiple symmetrical foci of osteosclerosis. They had both been diagnosed earlier with Calvé-Legg-Perthes disease, which on revision most likely represented Buschke-Ollendorff syndrome. Buschke-Ollendorff syndrome may imitate Calvé-Legg-Perthes disease. Skin signs may be the clue to diagnosis. Main differentials are sclerotic bone metastases and osteoma.


Assuntos
Doença de Legg-Calve-Perthes/diagnóstico , Osteopecilose/diagnóstico , Dermatopatias Genéticas/diagnóstico , Adulto , Criança , Erros de Diagnóstico , Feminino , Humanos , Doença de Legg-Calve-Perthes/diagnóstico por imagem , Doença de Legg-Calve-Perthes/patologia , Masculino , Mães , Osteopecilose/diagnóstico por imagem , Osteopecilose/patologia , Dermatopatias Genéticas/diagnóstico por imagem , Dermatopatias Genéticas/patologia
16.
J Pediatr Orthop B ; 24(2): 89-94, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25305048

RESUMO

A quantitative method to assess hip synovitis in Legg-Calvé-Perthes disease (LCPD) is not currently available. To develop this method, the areas of synovial enhancement on gadolinium-enhanced MRI (Gd-MRI) were measured by two independent observers. The volume of synovial enhancement was significantly increased in the initial and the fragmentation stages of LCPD (Waldenström stages I and II), with a persistence of synovitis into the reossification stage (stage III). The Gd-MRI method had high interobserver and intraobserver agreements and may serve as a useful method to monitor the effect of various treatments on hip synovitis in LCPD.


Assuntos
Cabeça do Fêmur/patologia , Doença de Legg-Calve-Perthes/diagnóstico , Imageamento por Ressonância Magnética/métodos , Sinovite/diagnóstico , Criança , Pré-Escolar , Meios de Contraste , Feminino , Gadolínio , Articulação do Quadril/patologia , Humanos , Doença de Legg-Calve-Perthes/diagnóstico por imagem , Doença de Legg-Calve-Perthes/patologia , Masculino , Variações Dependentes do Observador , Estudos Prospectivos , Radiografia
17.
J Bone Joint Surg Am ; 96(14): 1152-1160, 2014 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-25031369

RESUMO

BACKGROUND: Current radiographic classifications for Legg-Calvé-Perthes disease cannot be applied at the early stages of the disease. The purpose of this study was to quantify the perfusion of the femoral epiphysis in the early stages of Legg-Calvé-Perthes disease with use of perfusion magnetic resonance imaging (MRI) and to determine if the extent of epiphyseal perfusion can predict the lateral pillar involvement at the mid-fragmentation stage. METHODS: Twenty-nine patients had gadolinium-enhanced perfusion MRI at the initial stage or early fragmentation stage of Legg-Calvé-Perthes disease and were followed prospectively. The percent perfusion of the whole epiphysis and its lateral third was measured by four independent observers using image analysis software. The radiographs obtained at the mid-fragmentation stage were used for the lateral pillar classification. Intraclass correlation coefficient (ICC) and logistic regression analyses were performed. RESULTS: The mean age (and standard deviation) at diagnosis was 7.7 ± 1.7 years (range, 5.3 to 11.3 years). The mean interval between the MRI and the time of maximum fragmentation was 8.2 ± 5.5 months. The interobserver ICC for the percent perfusion of the lateral third of the epiphysis was 0.90 (95% confidence interval [CI]: 0.83 to 0.95). The mean percent perfusion of the lateral third of the epiphysis was 92% ± 2%, 68% ± 18%, and 46% ± 12% for the hips in which the lateral pillar was later classified as A, B, and C, respectively (p = 0.001). When the perfusion level was ≥90% in the lateral third of the epiphysis, the odds ratio of the lateral pillar being later classified as group A, as opposed to B or C, was 72.0 (CI: 3.5 to 1476). With a perfusion level of ≤55% in the lateral third of the epiphysis, the odds ratio of the lateral pillar being later classified as group C, as opposed to A or B, was 33.3 (CI: 2.8 to 392). Similar results were obtained for the whole epiphysis. CONCLUSIONS: Perfusion MRI measurements of the total epiphysis and its lateral third obtained at the early stages of Legg-Calvé-Perthes disease were predictive of lateral pillar involvement at the mid-fragmentation stage of the disease. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Cabeça do Fêmur/diagnóstico por imagem , Doença de Legg-Calve-Perthes/diagnóstico por imagem , Angiografia por Ressonância Magnética , Criança , Pré-Escolar , Epífises/diagnóstico por imagem , Feminino , Cabeça do Fêmur/patologia , Humanos , Doença de Legg-Calve-Perthes/complicações , Doença de Legg-Calve-Perthes/patologia , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos
18.
Rev Esp Cir Ortop Traumatol ; 58(2): 68-77, 2014.
Artigo em Espanhol | MEDLINE | ID: mdl-24439851

RESUMO

OBJECTIVE: To establish a simple, reproducible and safe experimental model, for the development of ischemic vascular necrosis of the hip in the lamb. MATERIAL AND METHODS: We used 15 lambs (10 males and 5 females) aged four weeks, divided into a control group (7 animals) and an experimental group (8 animals) producing ischemia in the proximal femur. Standard radiography and MRI were performed. The animals were euthanised at the 4th, 8th and 12th weeks after surgery. The femoral heads were extracted and measured and a histological analysis was performed with hematoxylin-eosin staining. RESULTS: Decreased height and increased width of the femoral head was observed in the X-Rays, particularly after the 4th week. We did not observe any changes in the height of the lateral pillar or trochanteric distance. The experimental group showed macroscopical hypertrophy and progressive flattening of the head. At 4 weeks necrotic areas in articular cartilage were observed, bone marrow was dense and the growth cartilage height was lower. The vessels were thickened by proliferation of the medial and adventitia layers. At 8 weeks, we found fibrosis in the subchondral bone with thinned and devitalized angiogenesis fat areas. The articular cartilage showed irregularities. At 12 weeks the closure of the physis was noted, as well as chondral areas in the trabecular bone and fat cells in the methaphysis. CONCLUSION: Although the histological changes are consistent with necrosis of the femoral head, the images obtained did not resemble Perthes disease, so we do not advise this experimental model for the study of this disease.


Assuntos
Modelos Animais de Doenças , Doença de Legg-Calve-Perthes , Animais , Feminino , Doença de Legg-Calve-Perthes/patologia , Masculino , Ovinos
19.
Biomed Res Int ; 2013: 859483, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24377097

RESUMO

The aim of the study was to retrospectively review results of operative treatment for coverage deficit of femoral head in children with severe epiphysis displacement in Legg-Calvé-Perthes (LCP) disease. The material included 23 shelf acetabuloplasty procedures for LCP disease. The average age at diagnosis was 8.1 years (range 4-12). Mean follow-up was 5.8 years (range from 2.2 to 11.2 years). Mean Reimer's index decreased statistically significantly from a mean of 32% before surgery to 10.0% at the last follow-up (P < 0.00001). The mean Wiberg center-edge angle increased also statistically significantly from a mean of 17.3° before procedure to 32.3° at the last follow-up (P < 0.00001). According to the Stulberg classification, type I was observed in 2, type II in 13, type III in 6, and type IV in 2 hips. There were no differences in the range of motion or leg length discrepancy in preoperative and postoperative standing. Partial, not significant, bone graft resorption was noted in 6 cases in the first 6-9 months after surgery. To conclude, shelf acetabuloplasty allows achieving good midterm results in the treatment of severe stages of LCP disease. The procedure improves coverage of femoral head and allows its remodelling.


Assuntos
Epífises/cirurgia , Cabeça do Fêmur/cirurgia , Doença de Legg-Calve-Perthes/cirurgia , Criança , Pré-Escolar , Epífises/patologia , Feminino , Cabeça do Fêmur/patologia , Seguimentos , Humanos , Doença de Legg-Calve-Perthes/patologia , Masculino , Amplitude de Movimento Articular , Resultado do Tratamento
20.
J Bone Joint Surg Am ; 95(5): 417-23, 2013 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-23467864

RESUMO

BACKGROUND: Coxa profunda is commonly viewed as a radiographic parameter that is indicative of pincer-type femoroacetabular impingement, and this finding can impact diagnostic and surgical decision-making. Validation of coxa profunda as a measure of pincer-type femoroacetabular impingement has not been rigorously analyzed. Our hypothesis was that coxa profunda is a very common radiographic finding in females and is not a finding that is specifically associated with pincer-type femoroacetabular impingement. METHODS: A retrospective review was performed to determine the prevalence of coxa profunda in four groups of hips: those with acetabular dysplasia (fifty-eight hips), femoroacetabular impingement (fifty hips), symptomatic residual Legg-Calvé-Perthes deformities (sixteen hips), and asymptomatic hips (thirty-three). Coxa profunda was present when the floor of the acetabular fossa touched or was medial to the ilioischial line. The association between coxa profunda and hip disorder diagnosis, lateral center-edge angle, acetabular inclination, patient age, and sex was analyzed. RESULTS: Coxa profunda was seen in 55% of the 157 hips and was slightly less common in the hips with acetabular dysplasia or residual Legg-Calvé-Perthes deformities (41% and 31%, respectively). Coxa profunda was evident in 76% of the thirty-three asymptomatic hips compared with 64% of the fifty hips with femoroacetabular impingement. Coxa profunda was more common in females than males (70% compared with 24%; p < 0.001). Acetabular overcoverage (a lateral center-edge angle of >40° or acetabular inclination of <0°) was seen in only 22% of hips with coxa profunda. CONCLUSIONS: Coxa profunda should be considered a normal radiographic finding, at least in females. Coxa profunda is a nonspecific radiographic finding, seen in a variety of hip disorders and asymptomatic hips. The presence of coxa profunda is neither necessary nor sufficient to support a diagnosis of pincer-type femoroacetabular impingement.


Assuntos
Acetábulo/diagnóstico por imagem , Impacto Femoroacetabular/diagnóstico por imagem , Articulação do Quadril/diagnóstico por imagem , Acetábulo/anatomia & histologia , Acetábulo/patologia , Adolescente , Adulto , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Impacto Femoroacetabular/patologia , Luxação do Quadril/diagnóstico por imagem , Luxação do Quadril/patologia , Articulação do Quadril/anatomia & histologia , Articulação do Quadril/patologia , Humanos , Doença de Legg-Calve-Perthes/diagnóstico por imagem , Doença de Legg-Calve-Perthes/patologia , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Fatores Sexuais , Adulto Jovem
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