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1.
Eur Cell Mater ; 45: 88-112, 2023 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-36989118

RESUMEN

Because low back pain is frequently a result of intervertebral disc degeneration (IVDD), strategies to regenerate or repair the IVD are currently being investigated. Often, ex vivo disc cultures of non-human IVD organs or tissue explants are used that usually do not exhibit natural IVDD. Therefore, degenerative changes mimicking those reported in human IVDD need to be induced. To support researchers in selecting ex vivo disc cultures, a systematic search was performed for them and their potential use for studying human IVDD reviewed. Five degeneration induction categories (proinflammatory cytokines, injury/damage, degenerative loading, enzyme, and other) were identified in 129 studies across 7 species. Methods to induce degeneration are diverse and can induce mild to severe degenerative changes that progress over time, as described for human IVDD. The induced degenerative changes are model-specific and there is no "one-fits-all" IVDD induction method. Nevertheless, specific aspects of human IVDD can be well mimicked. Currently, spontaneously degenerated disc cultures from large animals capture human IVDD in most aspects. Combinatorial approaches of several induction methods using discs derived from large animals are promising to recapitulate pathological changes on several levels, such as cellular behaviour, extracellular matrix composition, and biomechanical function, and therefore better mimic human IVDD. Future disc culture setups might increase in complexity, and mimic human IVDD even better. As ex vivo disc cultures have the potential to reduce and even replace animal trials, especially during preclinical development, advancement of such models is highly relevant for more efficient and cost-effective clinical translation from bench-to-bedside.


Asunto(s)
Degeneración del Disco Intervertebral , Disco Intervertebral , Animales , Disco Intervertebral/patología , Degeneración del Disco Intervertebral/patología , Citocinas , Matriz Extracelular
2.
J Biomech ; 129: 110756, 2021 12 02.
Artículo en Inglés | MEDLINE | ID: mdl-34619461

RESUMEN

Neutral zone (NZ) is an important biomechanical parameter when evaluating spinal instability following destabilizing and restabilizing events, with particular relevance for implant efficacy testing. It remains unclear what NZ calculation methods are most sensitive at capturing NZ changes across treatment conditions and a direct comparison is needed. The purpose of this study was to determine the most sensitive method at quantifying instability in human spines. Six cadaveric lumbar motion segments were subjected to a repeated measures implant testing schema of four sequential conditions: (1) Intact, (2) injury by herniation, (3) device implantation, (4) long-term cyclic fatigue loading. NZ was expected to increase after destabilization (steps 2 & 4) and decrease after restabilization (step 3). NZ methods compared in this study were: trilinear (TL), double sigmoid (DS), zero load (ZL), stiffness threshold (ST), and extrapolated elastic zone (EEZ). TL, ZL, and EEZ identified statistically significant NZ differences after each condition in flexion/extension and lateral bending. The ZL method also captured differences in axial rotation. All methods identified expected NZ changes after destabilization and restabilization, except DS in axial rotation. The TL, ZL, and EEZ methods were the most sensitive methods with this human cadaveric dataset. Future investigations comparing methods with additional datasets will clarify outcome generalizability and determine what curve profiles are most suitable for DS and ST methods. Understanding the applicability of NZ methods can enhance rigor and reliability of spinal instability measurements when quantifying the efficacy of novel implants and permits insight into clinically relevant biomechanical changes.


Asunto(s)
Vértebras Lumbares , Prótesis e Implantes , Fenómenos Biomecánicos , Cadáver , Humanos , Rango del Movimiento Articular , Reproducibilidad de los Resultados
3.
Eur Cell Mater ; 42: 1-19, 2021 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-34235715

RESUMEN

Mesenchymal stem/stromal cell (MSC)-based therapies have been proposed for back pain and disc degeneration, despite limited knowledge on their mechanism of action. The impact of MSCs/their secretome on annulus fibrosus (AF) cells and tissue was analysed in bovine AF organ cultures (AF-OCs) exposed to upper-physiological cyclic tensile strain (CTS, 9 %, 1 Hz, 3 h/d) and interleukin (IL)-1ß in a custom-made device. A 4 d treatment of the CTS + IL-1ß-stimulated AF-OCs with MSC secretome downregulated the expression of inflammation markers [IL-6, IL-8, prostaglandin-endoperoxide synthase 2 (PTGS2)], complement system regulators [cluster of differentiation (CD)46, CD55, CD59] and matrix metalloproteinase 1 but also of tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2) and collagen type I. At the protein level, it was confirmed that IL-6, MMP-3 and collagen content was decreased in AF-OCs treated with the MSC secretome compared to the CTS + IL-1ß stimulation alone. 9 d after treatment, a biomechanical peel-force test showed that the annular adhesive strength was significantly decreased by the MSC secretome treatment. Overall, MSC secretome had a stronger impact on AF tissue than MSCs in co-culture. The secretome contributed to a decrease in the inflammatory and catabolic status of AF cells activated by CTS + IL-1ß and played a role in the regulation of the complement system. However, it also contributed to a decrease in collagen at the gene/protein level and in AF mechanical strength compared to the CTS + IL-1ß stimulation alone. Therefore, the use of MSC secretome requires further investigation regarding its influence on disc matrix properties.


Asunto(s)
Anillo Fibroso , Células Madre Mesenquimatosas , Animales , Anillo Fibroso/metabolismo , Bovinos , Células Cultivadas , Técnicas de Cultivo de Órganos , Secretoma
4.
Eur Cell Mater ; 41: 388-400, 2021 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-33745125

RESUMEN

For spinal load and muscle force estimation as well as for numerical model and experimental setup validation, data on human intradiscal pressure are essential. Therefore, the aim of the present meta-analysis was to summarise all in vitro measurements of human intradiscal pressure performed under defined boundary conditions, i.e. without external loading (intrinsic pressure), under axial loading (compression, traction, shear) and under single-planar bending loading (flexion, extension, lateral bending, axial rotation). Data were evaluated based on segmental level and normalised to force and moment. Regression analysis was performed to investigate coefficients of determination and statistical significance of relationships between intradiscal pressure and segmental level for the single loading conditions. 35 studies fulfilled the inclusion criteria, from which a total of 451 data points were collected for the meta-analysis. High coefficients of determination were found in axial compression (r2 = 0.875) and flexion (r2 = 0.781), while being low for intrinsic pressure (r2 = 0.266) and lateral bending (r2 = 0.385), all showing significant regression fitting (p < 0.01). Intradiscal pressure decreases from the upper cervical spine to the sacrum in all loading conditions, considering the same amount of loading for all segmental levels, while the intrinsic pressure exhibits a minimum of the regression curve in the mid-thoracic spine. Apart from its potential for numerical and experimental model validation, this dataset may help to understand the load distribution along the human spine.


Asunto(s)
Columna Vertebral/fisiología , Soporte de Peso/fisiología , Humanos , Disco Intervertebral/fisiología , Presión , Rotación
5.
J R Soc Interface ; 16(151): 20180793, 2019 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-30958193

RESUMEN

The present study deals with the characterization of bone quality in a sheep model of postmenopausal osteoporosis. Sheep were sham operated ( n = 7), ovariectomized ( n = 6), ovariectomized and treated with deficient diet ( n = 8) or ovariectomized, treated with deficient diet and glucocorticoid injections ( n = 7). The focus of the study is on the microscopic properties at tissue level. Microscopic mechanical properties of osteoporotic bone were evaluated by a combination of biomechanical testing and mathematical modelling. Sample stiffness and strength were determined by compression tests and finite-element analysis of stress states was conducted. From this, an averaged microscopic Young's modulus at tissue level was determined. Trabecular structure as well as mineral and collagen distribution in samples of sheep vertebrae were analysed by micro-computed tomography and time-of-flight secondary ion mass spectrometry. In the osteoporotic sheep model, a disturbed fibril structure in the triple treated group was observed, but bone loss only occurred in form of reduced trabecular number and thickness and cortical decline, while quality of the residual bone was preserved. The preserved bone tissue properties in the osteoporotic sheep model allowed for an estimation of bone strength which behaves similar to the human case.


Asunto(s)
Densidad Ósea , Módulo de Elasticidad , Osteoporosis , Columna Vertebral , Microtomografía por Rayos X , Animales , Modelos Animales de Enfermedad , Femenino , Análisis de Elementos Finitos , Humanos , Osteoporosis/diagnóstico por imagen , Osteoporosis/metabolismo , Ovinos , Columna Vertebral/diagnóstico por imagen , Columna Vertebral/metabolismo
6.
Biomech Model Mechanobiol ; 16(2): 537-547, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27664020

RESUMEN

The two main load bearing tissues of the intervertebral disc are the nucleus pulposus and the annulus fibrosus. Both tissues are composed of the same basic components, but differ in their organization and relative amounts. With degeneration, the clear distinction between the two tissues disappears. The changes in biochemical content lead to changes in mechanical behaviour of the intervertebral disc. The aim of the current study was to investigate if well-documented moderate degeneration at the biochemical and fibre structure level leads to instability of the lumbar spine. By taking into account biochemical and ultrastructural changes to the extracellular matrix of degenerating discs, a set of constitutive material parameters were determined that described the individual tissue behaviour. These tissue biomechanical models were then used to simulate dynamic behaviour of the degenerated spinal motion segment, which showed instability in axial rotation, while a stabilizing effect in the other two principle bending directions. When a shear load was applied to the degenerated spinal motion segment, no sign of instability was found. This study found that reported changes to the nucleus pulposus and annulus fibrosus matrix during moderate degeneration lead to a more stable spinal motion segment and that such biomechanical considerations should be incorporated into the general pathophysiological understanding of disc degeneration and how its progress could affect low back pain and its treatments thereof.


Asunto(s)
Degeneración del Disco Intervertebral/fisiopatología , Disco Intervertebral/fisiología , Vértebras Lumbares/fisiología , Modelos Biológicos , Fenómenos Biomecánicos , Simulación por Computador , Matriz Extracelular/química , Humanos , Disco Intervertebral/química
7.
Osteoarthritis Cartilage ; 24(4): 679-87, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26687822

RESUMEN

OBJECTIVE: To study the role of mitogen-activated protein kinases (MAPKs) in human annulus fibrosus (AF) cells subjected to cyclic tensile stress (CTS). DESIGN: An in vitro system for CTS studies was established using AF cultures on fibronectin-coated silicone dishes. MAPK phosphorylation was studied by western analysis, while gene expression was followed by qRT-PCR. DNA synthesis was assessed by both tritiated thymidine incorporation and flow cytometry, and collagen synthesis using tritiated proline incorporation and the protease-free collagenase method. RESULTS: All three MAPKs studied, i.e., ERK, SAPK/JNK, and p38 were found to be phosphorylated immediately after CTS application within physiological range. A second wave of phosphorylation appeared at later time points. MAPK activation was elevated at higher CTS magnitudes, but independent of the frequency. CTS did not stimulate DNA synthesis neither extracellular matrix turnover, but it stimulated the proinflammatory genes, COX-2, IL-6, and IL-8. This stimulation was more intense at the highest magnitude (8%) tested and at the median frequency (1 Hz) and time interval (12 h). Blocking of ERK, SAPK/JNK, and p38 MAPK inhibited the CTS-induced stimulation of COX-2 and IL-8, while IL-6 expression was mediated only by SAPK/JNK and p38 MAPK. CONCLUSIONS: We have described for the first time the activation of MAPKs in human AF cells in response to CTS and showed that it drives an inflammatory reaction. These observations shed light on the mechanisms of intervertebral disc (IVD) cell responses to mechanical stress, contributing to the understanding of disc pathophysiology and possibly to the design of novel therapeutic interventions.


Asunto(s)
Anillo Fibroso/citología , Mediadores de Inflamación/metabolismo , Mecanotransducción Celular/fisiología , Proteínas Quinasas Activadas por Mitógenos/biosíntesis , Adolescente , Adulto , Anillo Fibroso/enzimología , Anillo Fibroso/metabolismo , Células Cultivadas , Activación Enzimática/fisiología , Femenino , Regulación de la Expresión Génica/fisiología , Humanos , Masculino , Mecanotransducción Celular/genética , Persona de Mediana Edad , Proteínas Quinasas Activadas por Mitógenos/fisiología , Fosforilación/fisiología , Estrés Mecánico , Adulto Joven
8.
Unfallchirurg ; 118 Suppl 1: 4-11, 2015 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-26495451

RESUMEN

The objective of this article is to summarize the history of the German Spine Society (DWG). This society resulted in the year 2006 after several attempts from the fusion of two established German societies, which were dealing with topics around the spine, der "German Society for Spine Research" founded in the year 1958 and the "German Society for Spine Surgery" founded in the year 1987. This fusion was the beginning of a success story, as from this time on the annual membership increased so much that the DWG became the largest spine society in Europe and one of all spine societies worldwide.


Asunto(s)
Sociedades Médicas/historia , Enfermedades de la Columna Vertebral/historia , Traumatología/historia , Alemania , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Relaciones Interinstitucionales , Ortopedia/historia
9.
Unfallchirurg ; 118(10): 822-30, 2015 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-26358323

RESUMEN

BACKGROUND: With increasing age, bone mass decreases and the structure of the cancellous bone in the vertebral body changes. Especially in osteoporotic patients, but also with metastases in the vertebral body, this leads to decreased strength and, thus, to an increased risk of vertebral fractures. It is expected that this problem will increase significantly because of demographic developments. To treat or to prevent such vertebral fractures, different augmentation techniques have been developed. They can mainly be divided into vertebroplasty or kyphoplasty procedures. PURPOSE: The goal of this paper is to summarize biomechanical aspects of these augmentations procedures and to present some alternative methods. MATERIALS AND METHODS: With vertebroplasty, the loss of bone mass is balanced by injecting bone cement which improves the failure strength of the affected vertebral body. With kyphoplasty, cavities are created and these are filled with bone cement. RESULTS: Disadvantages of vertebroplasty are uncontrollable cement extrusion and increased fracture risk in the adjacent vertebral bodies. With balloon kyphoplasty, the adjacent cancellous bone is compacted during dilation and, thus, does not allow good integration with the remaining trabeculae. In addition, this method is associated with an increased risk of fracture in the adjacent vertebrae. To counter these disadvantages, a number of new types of cement and alternative augmentation methods are being developed, with which the vertebral body may be filled or distracted. CONCLUSION: The efficacy of these new methods should be tested in appropriate experimental biomechanical studies before they are used in patients.


Asunto(s)
Cementos para Huesos/uso terapéutico , Osteotomía/métodos , Fracturas de la Columna Vertebral/fisiopatología , Fracturas de la Columna Vertebral/terapia , Vertebroplastia/métodos , Fuerza Compresiva , Humanos , Osteotomía/instrumentación , Procedimientos de Cirugía Plástica/instrumentación , Procedimientos de Cirugía Plástica/métodos , Resistencia a la Tracción , Resultado del Tratamiento , Vertebroplastia/instrumentación
10.
J Biomech ; 47(8): 1757-66, 2014 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-24767702

RESUMEN

Finite element (FE) model studies have made important contributions to our understanding of functional biomechanics of the lumbar spine. However, if a model is used to answer clinical and biomechanical questions over a certain population, their inherently large inter-subject variability has to be considered. Current FE model studies, however, generally account only for a single distinct spinal geometry with one set of material properties. This raises questions concerning their predictive power, their range of results and on their agreement with in vitro and in vivo values. Eight well-established FE models of the lumbar spine (L1-5) of different research centers around the globe were subjected to pure and combined loading modes and compared to in vitro and in vivo measurements for intervertebral rotations, disc pressures and facet joint forces. Under pure moment loading, the predicted L1-5 rotations of almost all models fell within the reported in vitro ranges, and their median values differed on average by only 2° for flexion-extension, 1° for lateral bending and 5° for axial rotation. Predicted median facet joint forces and disc pressures were also in good agreement with published median in vitro values. However, the ranges of predictions were larger and exceeded those reported in vitro, especially for the facet joint forces. For all combined loading modes, except for flexion, predicted median segmental intervertebral rotations and disc pressures were in good agreement with measured in vivo values. In light of high inter-subject variability, the generalization of results of a single model to a population remains a concern. This study demonstrated that the pooled median of individual model results, similar to a probabilistic approach, can be used as an improved predictive tool in order to estimate the response of the lumbar spine.


Asunto(s)
Análisis de Elementos Finitos , Vértebras Lumbares/fisiología , Modelos Teóricos , Algoritmos , Fuerza Compresiva , Humanos , Vértebras Lumbares/anatomía & histología , Postura , Presión , Probabilidad , Rango del Movimiento Articular/fisiología , Reproducibilidad de los Resultados , Rotación , Articulación Cigapofisaria/fisiología
11.
Transplant Proc ; 43(7): 2683-6, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21911146

RESUMEN

It is well established that patients presenting for orthotopic liver transplantation pose challenging surgical and anesthesiological problems. Intraoperatively, severe hemodynamic instability due to profuse bleeding and acute cardiomyopathy during reperfusion are major concerns. In addition, ischemia-reperfusion injury can compromise postoperative graft function. Xenon, with its potential to maintain hemodynamic stability, preserve cardiac function, and protect the liver graft of the recipient, seems to be a promising anesthetic agent for liver transplant surgery. To date, xenon has not been used as an anesthetic in liver transplantations. We therefore have reported our initial experience with four patients who underwent orthotopic deceased donor liver transplantation under xenon anesthesia. Although all patients had advanced liver disease and experienced significant intraoperative bleeding, their intraoperative courses, including reperfusion, under xenon anesthesia were remarkably stable. The patients required only moderate, temporary catecholamine support, which was withdrawn at the end of the surgery. Xenon anesthesia for liver transplant procedures proved to be feasible. Immediate postoperative organ function was satisfactory in all patients.


Asunto(s)
Anestesia , Trasplante de Hígado , Xenón/administración & dosificación , Anciano , Femenino , Humanos , Cuidados Intraoperatorios , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico , Cuidados Posoperatorios
12.
Eur Spine J ; 20(4): 578-84, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21125299

RESUMEN

Early stages of intervertebral disc degeneration are postulated to cause instability. In the literature, however, some authors report the opposite. These contradictory positions are probably supported by the mostly small number of segments which are investigated. The aim of this project therefore was to investigate the influence of intervertebral disc degeneration on lumbar spine rotational stability using a large data set. The flexibility data from all spine specimens tested in our institute so far were collected in a large in vitro database. From this database, all lumbar spine specimens were selected, which had been tested for flexibility under pure moment loads of ±7.5 N m and for which radiographs were accessible. 203 segments met these criteria. Their radiographic degree of disc degeneration was determined on a scale from 0 (no degeneration) to 3 (severe degeneration) and their influence on the respective range of motion and neutral zone was examined. The different lumbar levels differ in flexibility, which increases the variability of the data if pooled together. To minimise this effect a statistical model was fitted. The model-based mean estimates showed a decrease of the range of motion from grade 0 to 3 in flexion/extension (by 3.1°, p < 0.05) and lateral bending (by 3.4°, p < 0.05). In contrast, in axial rotation the range of motion tended to increase; however, not only from grade 0 to 1 but also towards grade 3 (by 0.2°) (p > 0.05). The neutral zone was affected in a similar way but to a smaller degree (p > 0.05). In conclusion, the results indicated that early stages of intervertebral disc degeneration do not necessarily cause rotational instability. In contrast, stability increased in flexion/extension and lateral bending. Only in axial rotation stability tended to decrease.


Asunto(s)
Degeneración del Disco Intervertebral/complicaciones , Inestabilidad de la Articulación/etiología , Vértebras Lumbares/fisiopatología , Rango del Movimiento Articular/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Fenómenos Biomecánicos , Bases de Datos como Asunto , Femenino , Humanos , Disco Intervertebral/diagnóstico por imagen , Disco Intervertebral/fisiopatología , Degeneración del Disco Intervertebral/diagnóstico por imagen , Degeneración del Disco Intervertebral/fisiopatología , Inestabilidad de la Articulación/diagnóstico por imagen , Inestabilidad de la Articulación/fisiopatología , Vértebras Lumbares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Radiografía , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Adulto Joven
13.
Orthopade ; 39(6): 565-72, 2010 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-20480134

RESUMEN

Interspinous spacers are commonly used to treat lumbar spinal stenosis or facet joint arthritis. The aims of implanting interspinous devices are to unload the facet joints, restore foraminal height, and provide stability especially in extension but still allow motion. This paper summarizes several in vitro studies, which compared four different interspinous implants - Coflex, Wallis, DIAM, and X-STOP - in terms of their three-dimensional primary stability, the intradiscal pressure, and stability after cyclic loading. 24 human lumbar spine specimens were divided into four equal groups and tested with pure moments in flexion/extension, lateral bending, and axial rotation: intact, after decompression with hemifacetectomy, and after implantation. Implantation had similar biomechanical effects with all four implants. In extension, they overcompensated the instability caused by the defect and restricted extension to about 50% compared to the intact state. In contrast, in flexion, lateral bending, and axial rotation the values of the range of motion stayed similar compared to the defective state. Intradiscal pressure after implantation was similar to that of the intact specimens in flexion, lateral bending, and axial rotation but much smaller during extension; 50,000 load cycles increased the range of motion in all motion planes by no more than 20%, but in extension motion this was still less than in the intact state.


Asunto(s)
Prótesis Articulares , Vértebras Lumbares/fisiopatología , Vértebras Lumbares/cirugía , Estenosis Espinal/fisiopatología , Estenosis Espinal/cirugía , Articulación Cigapofisaria/fisiopatología , Articulación Cigapofisaria/cirugía , Animales , Fuerza Compresiva , Módulo de Elasticidad , Análisis de Falla de Equipo , Humanos , Diseño de Prótesis
14.
Ann Oncol ; 19(5): 920-6, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18065406

RESUMEN

BACKGROUND: The study aimed to demonstrate the noninferiority of capecitabine to 5-fluorouracil (5-FU)/folinic acid (FA), in relation to progression-free survival (PFS) after first-line treatment of metastatic colorectal cancer and the benefit of adding celecoxib (C) to irinotecan/fluoropyrimidine regimens compared with placebo (P). PATIENTS AND METHODS: Patients were randomly assigned to receive FOLFIRI: irinotecan (180 mg/m(2) i.v. on days 1, 15 and 22); FA (200 mg/m(2) i.v. on days 1, 2, 15, 16, 29 and 30); 5-FU (400 mg/m(2) i.v. bolus, then 22-h, 600 mg/m(2) infusion) or CAPIRI: irinotecan (250 mg/m(2) i.v. infusion on days 1 and 22); capecitabine p.o. (1000 mg/m(2) b.i.d. on days 1-15 and 22-36). Patients were additionally randomly assigned to receive either placebo or celecoxib (800 mg: 2 x 200 mg b.i.d.). RESULTS: The trial was closed following eight deaths unrelated to disease progression in the 85 enrolled (629 planned) patients. Response rates were 22% for CAPIRI + C, 48% for CAPIRI + P, 32% for FOLFIRI + C and 46% for FOLFIRI + P. Median PFS and overall survival (OS) times were shorter for CAPIRI versus FOLFIRI (PFS 5.9 versus 9.6 months and OS 14.8 versus 19.9 months) and celecoxib versus placebo (PFS 6.9 versus 7.8 months and OS 18.3 versus 19.9 months). CONCLUSION: Due to the small sample size following early termination, no definitive conclusions can be drawn in relation to the noninferiority of CAPIRI compared with FOLFIRI.


Asunto(s)
Adenocarcinoma/secundario , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adenocarcinoma/tratamiento farmacológico , Adulto , Anciano , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Capecitabina , Celecoxib , Neoplasias Colorrectales/patología , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Diarrea/inducido químicamente , Método Doble Ciego , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/análogos & derivados , Humanos , Infusiones Intravenosas , Irinotecán , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Embolia Pulmonar/inducido químicamente , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , Choque Séptico/etiología , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Análisis de Supervivencia
15.
Clin Biomech (Bristol, Avon) ; 23(2): 242-7, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17981380

RESUMEN

BACKGROUND: Interspinous spacers are mainly used to treat lumbar spinal stenosis and facet arthrosis. Biomechanically, they stabilise in extension but do not compensate instability in axial rotation and lateral bending. It would therefore be desirable to have an interspinous spacer available, which provides for more stability also in these two planes. At the same time, the intervertebral disc should not completely be unloaded to keep it viable. To meet these requirements, a new version of the Coflex interspinous implant was developed, called "Coflex rivet", which can be more rigidly attached to the spinous processes. The aim was to investigate whether this new implant compensates instability but still allows some load to be transferred through the disc. METHODS: Twelve human lumbar spine segments were equally divided into two groups, one for Coflex rivet and one for the original Coflex implant. The specimens were tested for flexibility under pure moment loads in the three main planes. These tests were carried out in the intact condition, after creation of a destabilising defect and after insertion of either of the two implants. Before implantation, the interspinous spacers were equipped with strain gauges to measure the load transfer. FINDINGS: Compared to the defect condition, both implants had a strong stabilising effect in extension (P<0.05). Coflex rivet also strongly stabilised in flexion and to a smaller degree in lateral bending and axial rotation (P<0.05). In contrast, in these three loading directions, the original Coflex implant could not compensate the destabilising effect of the defect (P>0.05). The bending moments transferred through the implants were highest in extension and flexion. Yet, they were no more than 1.2 Nm in median. INTERPRETATION: The new Coflex rivet seems be a suitable option to compensate instability. Its biomechanical characteristics might even make it suitable as an adjunct to fusion, which would be a new indication for this type of implant.


Asunto(s)
Vértebras Lumbares/cirugía , Dispositivos de Fijación Ortopédica , Prótesis e Implantes , Fenómenos Biomecánicos , Cadáver , Humanos , Técnicas In Vitro , Diseño de Prótesis , Rango del Movimiento Articular , Rotación , Estadísticas no Paramétricas , Estrés Mecánico
16.
Eur Spine J ; 16(12): 2186-92, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17721711

RESUMEN

Pre-clinical in vitro tests are needed to evaluate the biomechanical performance of new spinal implants. For such experiments large animal models are frequently used. Whether these models allow any conclusions concerning the implant's performance in humans is difficult to answer. The aim of the present study was to investigate whether calf, pig or sheep spine specimens may be used to replace human specimens in in vitro flexibility and cyclic loading tests with two different implant types. First, a dynamic and a rigid fixator were tested using six human, six calf, six pig and six sheep thoracolumbar spine specimens. Standard flexibility tests were carried out in a spine tester in flexion/extension, lateral bending and axial rotation in the intact state, after nucleotomy and after implantation. Then, the Coflex interspinous implant was tested for flexibility and intradiscal pressure using another six human and six calf lumbar spine segments. Loading was carried out as described above in the intact condition, after creation of a defect and after implantation. The fixators were most easily implantable into the calf. Qualitatively, they had similar effects on ROM in all species, however, the degree of stability achieved differed. Especially in axial rotation, the ROM of sheep, pig and calf was partially less than half the human ROM. Similarly, implantation of the Coflex interspinous implant caused the ROM to either increase in both species or to decrease in both of them, however, quantitatively, differences were observed. This was also the case for the intradiscal pressure. In conclusion, animal species, especially the calf, may be used to get a first idea of how a new pedicle screw system or an interspinous implant behaves in in vitro flexibility tests. However, the effects on ROM and intradiscal pressure have to be expected to differ in magnitude between animal and human. Therefore, the last step in pre-clinical implant testing should always be an experiment with human specimens.


Asunto(s)
Bovinos/fisiología , Modelos Biológicos , Prótesis e Implantes , Ovinos/fisiología , Columna Vertebral/fisiología , Sus scrofa/fisiología , Adulto , Animales , Fenómenos Biomecánicos , Bovinos/anatomía & histología , Humanos , Disco Intervertebral/anatomía & histología , Disco Intervertebral/fisiología , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/instrumentación , Procedimientos Neuroquirúrgicos/métodos , Prótesis e Implantes/normas , Rango del Movimiento Articular/fisiología , Ovinos/anatomía & histología , Enfermedades de la Columna Vertebral/cirugía , Fusión Vertebral/instrumentación , Fusión Vertebral/métodos , Columna Vertebral/anatomía & histología , Sus scrofa/anatomía & histología , Soporte de Peso/fisiología
17.
J Orthop Res ; 25(11): 1513-22, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17568421

RESUMEN

Intervertebral discs (IVD) have a higher extracellular osmolarity than most other tissues; moreover their osmolarity changes by around 25% during each diurnal cycle. In this study, changes in aggrecan, collagen I and collagen II expression of IVD cells were examined after exposure to osmotic environment alterations or mechanical stimulation under different osmotic conditions. Human and bovine IVD cells seeded in three-dimensional (3D) collagen type I matrices were cultured under hypo-osmotic (300 mOsm), iso-osmotic (400 mOsm), or hyperosmotic (500 mOsm) conditions. Osmolarity-induced changes in gene expression of IVD cells were measured after 5 days. Load-induced changes in gene expression under the different osmotic conditions were measured after application of hydrostatic pressure (0.25 MPa, 0.1 Hz, 30 min) or cyclic strain (4%, 1 Hz, 24 h). The results showed that IVD cells respond strongly to changes in the osmotic environment by altering mRNA expression. Human cells cultured over 5 days increased expression of aggrecan and collagen II in both nucleus and annulus cells under increasing osmolarity. In contrast, collagen I expression was inhibited at high osmolarity in both cell types. Mechanically induced alterations in gene expression appear to have only modest effects on matrix protein expression, but the same stimulus partly resulted in an inhibition or stimulation of gene expression, depending on the osmotic conditions. This study showed that the osmotic environment does not only have an appreciable effect on gene expression but also affects responses to mechanical stimuli. This suggests that the osmotic conditions cannot be ignored when examining physiological and pathological behavior of IVD cells.


Asunto(s)
Agrecanos/metabolismo , Colágeno Tipo II/metabolismo , Colágeno Tipo I/metabolismo , Regulación de la Expresión Génica/fisiología , Disco Intervertebral/metabolismo , Adulto , Anciano , Agrecanos/genética , Animales , Bovinos , Células Cultivadas , Colágeno Tipo I/genética , Colágeno Tipo II/genética , Femenino , Humanos , Presión Hidrostática , Disco Intervertebral/citología , Masculino , Persona de Mediana Edad , Concentración Osmolar , ARN Mensajero/metabolismo , Estrés Mecánico , Soporte de Peso
18.
Eur Spine J ; 16(7): 987-92, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17426992

RESUMEN

To better understand the role of facet joint degeneration in chronic neck and back pain epidemiological and morphological data are needed. For the cervical spine, however, such data are rare. Therefore, the aim of this study was to determine the degree of cartilage degeneration of cervical facet joints with respect to spinal level and age, to investigate whether any region of the joint surface is more often affected by degeneration and to determine the localisation of osteophytes. A total of 128 left-sided facet surfaces from 15 fresh frozen cervical spine specimens (59-92 years) including in maximum C2-C7 were inspected in a way to ensure a direct comparability to data reported for the lumbar spine. First, the macroscopic degree of cartilage degeneration was determined and correlated to spinal level and age. Then, each facet surface was divided into five regions (anterior, posterior, lateral, medial and central) to check whether cartilage degeneration occurs more often in any of these regions. Finally, the localisation of osteophytes was determined. The results showed that the mean degree of cartilage degeneration was 2.8 (+/-0.6) on a scale from Grade 1 (no degeneration) to 4 (severe degeneration). None of all 128 facet surfaces was classified as Grade 1. All spinal levels had about the same degree of degeneration (in mean 2.5-3.0). The youngest age group (<70 years) had a somewhat lower degree of degeneration (2.6) than the oldest (> or = 90 years) (3.1). Cartilage defects were found all over the joint surfaces, none of the five regions was more often affected than the others. Least osteophytes were found on the medial border of the facet joints. In conclusion, the prevalence of cervical facet joint degeneration is probably very high in individuals aged 50 years and more, with a tendency to increase in severity with age. All levels of the middle and lower cervical spine were affected to almost the same degree, whereas in the lumbar spine an increase in degeneration towards the lower levels was reported. Also, in the cervical spine in most cases the cartilage was evenly degenerated all over the joint surface while in the lumbar spine certain regions were reported to be affected predominantly.


Asunto(s)
Vértebras Cervicales/patología , Disco Intervertebral/patología , Articulación Cigapofisaria/patología , Factores de Edad , Anciano , Anciano de 80 o más Años , Dolor de Espalda/etiología , Enfermedades de los Cartílagos/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor de Cuello/etiología
19.
Clin Biomech (Bristol, Avon) ; 21(7): 676-82, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16567025

RESUMEN

BACKGROUND: Vertebral compression fractures are counted among the most common complications of osteoporosis. For treatment, a new, alternative implant has been developed (BeadEx, Expandis, Hof HaCarmel, Israel). The aim of the present in vitro study was to evaluate whether this implant is able to restore the initial height and three-dimensional stability after fracture and whether it is able to maintain this height and stability during complex cyclic loading. METHODS: The BeadEx implant consists of small titanium rolls, which are pressed into the vertebral body through specially designed, hollow pedicle screws. The height and the three-dimensional flexibility of 18 bisegmental spine specimens (nine T12-L2, nine L3-L5) was measured, first, before and after creating a wedge compression fracture at the middle vertebral body (L1 resp. L4), second, after treatment of the fracture, and, third, during and after complex cyclic loading. The fractures were treated either with BeadEx plus internal fixator, BeadEx plus bone cement or vertebroplasty for comparison. FINDINGS: The height before fracture could almost be restored by BeadEx plus bone cement but not by BeadEx plus fixator and vertebroplasty. The total height loss after cyclic loading was smallest with BeadEx plus bone cement (in median -4.7mm with respect to the intact specimens) but -6.2mm with BeadEx plus fixator and -7.8mm with vertebroplasty. The three-dimensional stability of the specimens was clearly higher if treated with BeadEx plus fixator than with BeadEx plus bone cement or vertebroplasty. INTERPRETATION: From a biomechanical point of view, BeadEx plus bone cement can be recommended as an alternative to vertebroplasty in the treatment of osteoporotic vertebral body fractures. BeadEx plus fixator can be recommended if additional stability is needed.


Asunto(s)
Fracturas por Compresión/fisiopatología , Fracturas por Compresión/cirugía , Inestabilidad de la Articulación/fisiopatología , Osteoporosis/complicaciones , Fracturas de la Columna Vertebral/fisiopatología , Fracturas de la Columna Vertebral/cirugía , Fusión Vertebral/instrumentación , Fenómenos Biomecánicos/métodos , Placas Óseas , Tornillos Óseos , Cadáver , Análisis de Falla de Equipo , Fracturas por Compresión/etiología , Fracturas Espontáneas/etiología , Fracturas Espontáneas/fisiopatología , Fracturas Espontáneas/cirugía , Humanos , Técnicas In Vitro , Inestabilidad de la Articulación/etiología , Inestabilidad de la Articulación/prevención & control , Prótesis Articulares , Vértebras Lumbares/fisiopatología , Vértebras Lumbares/cirugía , Osteoporosis/fisiopatología , Osteoporosis/cirugía , Diseño de Prótesis , Rango del Movimiento Articular , Recuperación de la Función , Fracturas de la Columna Vertebral/complicaciones , Fusión Vertebral/métodos , Vértebras Torácicas/fisiopatología , Vértebras Torácicas/cirugía , Resultado del Tratamiento
20.
Eur Spine J ; 15(8): 1276-85, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16429291

RESUMEN

In recent years, non-fusion implants to stabilise the lumbar spine have become more and more popular. However, little is known on the load bearing of such dynamic stabilisation systems. In order to investigate the load bearing of discs bridged with rigid and dynamic stabilisation systems, six lumbar cadaver spines were mounted in a spine tester and loaded with pure moments in the three main motion planes. Four different states of the specimens were studied: intact, destabilised, stabilisation with a Dynesys and stabilisation with an internal fixator. Intradiscal pressure (IDP) measurements were used to assess the load bearing of the bridged disc. In the neutral unloaded position, there were small but not significant differences in disc pressure for the four states of the treated disc (P>0.05). Concerning the disc pressure during the course of loading, both the Dynesys and internal fixator did significantly reduce the pressure change from neutral to extension in comparison to the intact state (-0.05, -0.04 and +0.24 MPa, respectively) (P<0.05). Compared to the intact state, there was no significant pressure change from neutral to flexion (0.14, 0.15 and 0.18 MPa, respectively) (P>0.05). The devices apparently eliminated the pressure change from neutral to lateral bending (Dynesys 0.01 MPa, Fixator 0.01 MPa and intact 0.24 MPa), but due to large variations in the intact and defect states the differences were not significant (P>0.05). In axial rotation, the pressure change for the internal fixator was reduced compared to the intact state; however, the change was only significant in left axial rotation (P<0.05). The Dynesys showed no significant differences (P>0.05) in axial rotation. No changes in IDP were seen in the adjacent discs for either the Dynesys or the internal fixator. Our results showed that the IDPs for both devices were similar, but altered compared to the intact disc.


Asunto(s)
Artroplastia/instrumentación , Disco Intervertebral/fisiología , Vértebras Lumbares/fisiología , Adulto , Femenino , Humanos , Disco Intervertebral/cirugía , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Dispositivos de Fijación Ortopédica , Presión , Soporte de Peso
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