Transforaminal versus intra-articular facet steroid injections for the treatment of cervical radiculopathy : a randomized, double-blinded, controlled study.

Cette étude a été subventionnée par le Fonds de recherche du Québec - Santé (FRQ-S, grant # 21230 – 2)

Evaluating intra-articular drug delivery for the treatment of osteoarthritis in a rat model.

Osteoarthritis (OA) is a degenerative joint disease that can result in joint pain, loss of joint function, and deleterious effects on activity levels and lifestyle habits. Current therapies for OA are largely aimed at symptomatic relief and may have limited effects on the underlying cascade of joint degradation. Local drug delivery strategies may provide for the development of more successful OA treatment outcomes that have potential to reduce local joint inflammation, reduce joint destruction, offer pain relief, and restore patient activity levels and joint function. As increasing interest turns toward intra-articular drug delivery routes, parallel interest has emerged in evaluating drug biodistribution, safety, and efficacy in preclinical models. Rodent models provide major advantages for the development of drug delivery strategies, chiefly because of lower cost, successful replication of human OA-like characteristics, rapid disease development, and small joint volumes that enable use of lower total drug amounts during protocol development. These models, however, also offer the potential to investigate the therapeutic effects of local drug therapy on animal behavior, including pain sensitivity thresholds and locomotion characteristics. Herein, we describe a translational paradigm for the evaluation of an intra-articular drug delivery strategy in a rat OA model. This model, a rat interleukin-1beta overexpression model, offers the ability to evaluate anti-interleukin-1 therapeutics for drug biodistribution, activity, and safety as well as the therapeutic relief of disease symptoms. Once the action against interleukin-1 is confirmed in vivo, the newly developed anti-inflammatory drug can be evaluated for evidence of disease-modifying effects in more complex preclinical models.

Progress in intra-articular therapy.

Diarthrodial joints are well suited to intra-articular injection, and the local delivery of therapeutics in this fashion brings several potential advantages to the treatment of a wide range of arthropathies. Possible benefits over systemic delivery include increased bioavailability, reduced systemic exposure, fewer adverse events, and lower total drug costs. Nevertheless, intra-articular therapy is challenging because of the rapid egress of injected materials from the joint space; this elimination is true of both small molecules, which exit via synovial capillaries, and of macromolecules, which are cleared by the lymphatic system. In general, soluble materials have an intra-articular dwell time measured only in hours. Corticosteroids and hyaluronate preparations constitute the mainstay of FDA-approved intra-articular therapeutics. Recombinant proteins, autologous blood products and analgesics have also found clinical use via intra-articular delivery. Several alternative approaches, such as local delivery of cell and gene therapy, as well as the use of microparticles, liposomes, and modified drugs, are in various stages of preclinical development.

Estudo comparativo do uso de meloxicam por via intra-articular e sistêmica no controle da osteoartrite experimentalmente induzida em joelho de coelhos

Objective: This study aimed to evaluate morphologic changes, as well as chondroprotective and intra-articular effects of meloxicam on joint repair in rabbits induced by experimental trochleoplasty, minimizing possible adverse side effects. Methods: Thirty-five rabbits were divided into four groups: the control group, which did not undergo surgery, and operated groups, which used different ways of administering the anti-inflammatory agent: systemic, 0.2 mg/kg; intra-articular, 0.5 mg/kg; positive group control, without meloxicam. Each operated group was divided according to the periods of 7 or 30 days evaluation after surgery. Results: Regarding macroscopic and histological evaluation of cartilage, after 30 days, most animals showed almost complete joint repair, the presence of few or no inflammatory cells; whereas part of the animals treated with meloxicam presented necrosis in the trochlear ridge and absence of inflammatory cells after 7 days. In positive control group, it was observed moderate inflammation and connective tissue proliferation. None of the animals in the operated groups showed irregularities 30 days after surgery. Conclusion: Either intra-articular or systemic, meloxicam revealed to be favorable to be used for joint repair and control of inflammatory reaction. © 2013 Sociedade Brasileira de Ortopedia e Traumatologia.

The impact of early intra-articular corticosteroid injections on the outcome of oligoarticular juvenile idiopathic arthritis

Contexte Un objectif important de la prise en charge de l'arthrite juvénile oligoarticulaire serait d'altérer le cours de la maladie à l'aide d'une thérapie hâtive. Nous avons étudié l'effet des injections intra-articulaires de corticostéroïdes hâtives sur les chances d'atteindre un décompte d'articulation active de zéro et une maladie inactive. Méthode Les données démographiques, cliniques et thérapeutiques des patients avec oligoarthrite juvénile enrôlés dans une étude prospective longitudinale pancanadienne ont été collectées pendant 2 ans. Une injection hâtive était définie comme étant reçue dans les 3 premiers mois suivant le diagnostic. Les équations d'estimation généralisées ont été utilisées pour l'analyse statistique. Résultats Trois cent dix patients ont été inclus. Cent onze (35.8%) ont reçu une injection hâtive. Ces derniers avaient une maladie plus active lors de l'entrée dans l'étude. Les patients exposés à une injection hâtive avaient une chance similaire d'obtenir un décompte d'articulation active de zéro, OR 1.52 (IC95% 0.68-3.37), p=0.306 mais étaient significativement moins à risque d'avoir une maladie inactive, OR 0.35 (IC95% 0.14-0.88), p=0.026. Interprétation Dans cette cohorte de 310 patients avec oligoarthrite juvénile, les injections hâtives de corticostéroïdes n'ont pas mené à une probabilité plus élevée d'atteindre un décompte d'articulation active de zéro ou une maladie inactive. Des problématiques méthodologiques intrinsèques à l'utilisation de données observationnelles pour fins d'estimation d'effets thérapeutiques auraient pu biaiser les résultats. Nous ne pouvons affirmer avec certitude que les injections hâtives n'améliorent pas le décours de la maladie. Des études prospectives adressant les limitations soulevées seront requises pour clarifier la question.

Uso da S(+) cetamina por via intra-articular em modelo de osteoartrite em ratos: análise da imunoexpressão da ciclooxigenase 2

A osteoartrite (OA) é uma doença degenerativa que afeta grande parte da população e resulta em significativa morbidade e incapacidade. O presente estudo teve como objetivo investigar os efeitos periféricos da S(+) cetamina na expressão da ciclo-oxigenase 2 (COX-2). Foram utilizados modelos experimentais de osteoartrite em ratos. Inicialmente setenta e dois ratos foram utilizados no estudo. Foram divididos em três grupos de 24 animais cada. Em dois grupos foi induzida a OA através de 2mg de MIA (monoiodo acetato de sódio) por via intra-articular (i.a), em um volume máximo de 50μL e em um dos grupos não foi realizada a indução da OA. No sétimo dia após a indução, dois grupos, incluindo o sem OA, receberam injeção i.a de salina 0,9% em volume máximo de 50μL e o terceiro grupo recebeu injeção de S(+) cetamina na dose de 0,5mg/kg. Nos dias 7, 14, 21 e 28 os animais foram anestesiados e sacrificados para coleta da membrana sinovial e análise imuno-histoquímica da ciclo-oxigenase-2. Durante o estudo ocorreram 29 perdas do material a ser analisado, totalizando um n = 43. O protocolo adotado para a interpretação imuno-histoquímica foi a imunomarcação citoplasmática da COX-2 em células da membrana sinovial, tecido conjuntivo e adiposo, conforme a intensidade da coloração. A análise dos resultados foi realizada através do teste do quiquadrado. A reatividade da COX-2 foi positiva em 53,8% dos animais do grupo sem OA, em 60% do grupo OA com salina e em 80% dos animais do grupo OA com cetamina, sem diferença estatisticamente significante entre os grupos (p = 0,3069). Esse estudo sugeriu que a S(+) cetamina por via intra-articular não inibiu a expressão da COX-2 em modelos de osteoartrite em ratos.

An integrated analysis of five double-blind, randomized controlled trials evaluating the safety and efficacy of a hyaluronan product for intra-articular injection in osteoarthritis of the kneel

Objective: Five double-blind, randomized, saline-controlled trials (RCTs) were included in the United States marketing application for an intra-articular hyaluronan (IA-HA) product for the treatment of osteoarthritis (OA) of the knee. We report an integrated analysis of the primary Case Report Form (CRF) data from these trials. Method. Trials were similar in design, patient population and outcome measures - all included the Lequesne Algofunctional Index (LI), a validated composite index of pain and function, evaluating treatment over 3 months. Individual patient data were pooled; a repeated measures analysis of covariance was performed in the intent-to-treat (ITT) population. Analyses utilized both fixed and random effects models. Safety data from the five RCTs were summarized. Results: A total of 1155 patients with radiologically confirmed knee OA were enrolled: 619 received three or five IA-HA injections; 536 received. placebo saline injections. In the active and control groups, mean ages were 61.8 and 61.4 years; 62.4% and 58.8% were women; baseline total Lequesne scores 11.03 and 11.30, respectively. Integrated analysis of the pooled data set found a statistically significant reduction (P < 0.001) in total Lequesne score with hyaluronan (HA) (-2.68) vs placebo (-2.00); estimated difference -0.68 (95% CI: -0.56 to -0.79), effect size 0.20. Additional modeling approaches confirmed robustness of the analyses. Conclusions: This integrated analysis demonstrates that multiple design factors influence the results of RCTs assessing efficacy of intra-articular (IA) therapies, and that integrated analyses based on primary data differ from meta-analyses using transformed data. (C) 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Intra-articular pressure profiles of the cadaveric equine fetlock joint in motion

The study of the influence of motion and initial intra-articular pressure (IAP) on intra-articular pressure profiles in equine cadaver metatarsophalangeal (MTP) joints was undertaken as a prelude to in vivo studies, Eleven equine cadaver MTP joints were submitted to 2 motion frequencies of 5 and 10 cycles/min of flexion and extension, simulating the condition of lower and higher (double) rates of passive motion. These frequencies were applied and pressure profiles generated with initial normal intra-articular pressure (-5 mmHg) and subsequently 30 mmHg intra-articular pressure obtained by injection of previously harvested synovial fluid.The 4 trials performed were 1) normal IAP; 5 cyles/min; 2) normal IAP; 10 cycles/min; 3) IAP at 30 mmHg; 5 cycles/min and 4) IAP at 30 mmHg; 10 cycles/min. The range of joint motion applied (mean +/- s.e.) was 67.6 +/- 1.61 degrees with an excursion from 12.2 +/- 1.2 degrees in extension to 56.2 +/- 2.6 degrees in flexion, Mean pressure recorded in mmHg for the first and last min of each trial, respectively, were 1) -5.7 +/- 0.9 and -6.3 +/- 1.1; 2) -5.3 +/- 1.1 and -6.2 +/- 1.1; 3) 58.8 +/- 8.0 and 42.3 +/- 7.2; 4) 56.6 +/- 3.7 and 40.3 +/- 4.6. Statistical analyses showed a trend for difference between the values for the first and last minute in trial 3 (0.05>P<0.1) with P = 0.1 and significant difference (P = 0.02) between the mean IAP of the first and last min in trial 4. The loss of intra-articular pressure associated with time and motion was 10.5, 16.9, 28.1 and 28.9% for trials 1-4, respectively. As initial intraarticular pressure and motion increased, the percent loss of intra-articular pressure increased.The angle of lowest pressure was 12.2 +/- 1.2 (mean +/- s.e.) in extension in trials 1 and 2, In trials 3 and 4, the lowest pressures were obtained in flexion with the joints at 18.5 +/- 2.0 degrees (mean +/- s.e.). This demonstrated that the joint angle of least pressure changed as the initial intra-articular pressure changed and there would not be a single angle of least pressure for a given joint.The volume of synovial fluid recovered from the MTP joints in trial 3 compared to 4 (trials in which fluid was injected to attain IAP of 30 mmHg) was not significantly different, supporting a soft tissue compliance change as a cause for the significant loss of intra-articular pressure during the 15 min of trial 4.The pressure profiles generated correlate well with in vivo values and demonstrated consistent pressure profiles. Our conclusions are summarised as follows:1. Clinically normal equine MTP joints which were frozen and then later thawed were found to have mostly negative baseline intra-articular pressures, as would be expected in living subjects,2. Alternate pressure profiles of the dorsal and plantar pouch at baseline intra-articular pressure document the presence of pressure forces that would support 'back and forth' fluid movement between joint compartments. This should result in movement of joint fluid during motion, assisting in lubrication and nutrition of articular cartilage,3. If joint pressure was initially greater than normal (30 mmHg), as occurs in diseased equine MTP joints, joint motion further increased joint capsule relaxation (compliance) and, therefore, reduced intra-articular pressure.4. Peak intra-articular pressures reached extremely high values (often >100 mmHg) in flexion when initial pressure was 30 mmHg. Joint effusion pressures recorded for clinical MCP joints are frequently 30 mmHg. These IAP values are expected to produce intermittent synovial ischaemia in clinical cases during joint flexion.5, Additional in vivo studies are necessary to confirm our conclusions from this study and to identify the contributions of fluid absorption and the presence of ischaemia in a vascularised joint.

Estudo clínico-laboratorial das articulações de cães naturalmente infectados com leishmaniose visceral e experimentalmente inoculados com Leishmania chagasi por via intra-articular

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Método de utilização de membrana de celulose bacteriana intra articular sobre superfície lesada de patela

The present invention discloses the use of the bacterial cellulose membrane in ligament, tendon and synovial capsule reconstructions according to the methods described in the technical description of the invention. Said material could be used in the reconstruction of ligaments and tendons (the knee cruciate ligaments, patellar ligament, Achilles tendon, quadriceps tendon, etc.) and the synovial capsule.

T1 assessment of hip joint cartilage following intra-articular gadolinium injection: a pilot study

This pilot study defines the feasibility of cartilage assessment in symptomatic femoroacetabular impingement patients using intra-articular delayed gadolinium-enhanced MRI of cartilage (ia-dGEMRIC). Nine patients were scanned preliminary to study the contrast infiltration process into hip joint cartilage. Twenty-seven patients with symptomatic femoroacetabular impingement were subsequently scanned with intra-articular delayed gadolinium-enhanced MRI of cartilage. These T(1) findings were correlated to morphological findings. Zonal variations were studied. This pilot study demonstrates a significant difference between the pre- and postcontrast T(1) values (P < 0.001) remaining constant for 45 min. We noted higher mean T(1) values in morphologically normal-appearing cartilage than in damaged cartilage, which was statistically significant for all zones except the anterior-superior zone. Intraobserver (0.972) and interobserver correlation coefficients (0.933) were statistically significant. This study outlines the feasibility of intra-articular delayed gadolinium-enhanced MRI of cartilage for assessment of cartilage changes in patients with femoroacetabular impingement. It can also define the topographic extent and differing severities of cartilage damage.

Intravenous versus intra-articular delayed gadolinium-enhanced magnetic resonance imaging in the hip joint: a comparative analysis

The purpose of this study was to investigate whether T1-mapping of hip joint with intra-articular delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (ia-dGEMRIC) is comparable to the already established intravenous (iv)-technique for assessing different grades of cartilage degeneration.

Antinociceptive activity of pre- versus post-operative intra-articular bupivacaine in goats undergoing stifle arthrotomy

OBJECTIVE: To evaluate the peri-operative analgesic efficacy of intra-articular bupivacaine administered before or after stifle arthrotomy. STUDY DESIGN: Prospective, randomized, blind, placebo-controlled experimental trial. ANIMALS: Thirty-nine healthy goats. METHODS: The goats were allocated randomly to one of three intra-articular treatment groups: group PRE (bupivacaine before and saline after surgery), group POST (saline before and bupivacaine after surgery) and group CON (saline before and after surgery). Anaesthesia was maintained with a constant end-tidal sevoflurane of 2.5%. Intra-operatively heart rate (HR), respiratory rate and mean arterial blood pressure (MAP) after critical surgical events (CSE) were recorded and compared with pre-incision values. Propofol requirements to maintain surgical anaesthesia were recorded. Flunixin was administered for 5 days. Post-operative pain assessment at 20 minutes, 2 hours, 4 hours after recovery and on day 2 and 3 included a multidimensional pain score (MPS), a lameness score and mechanical nociceptive threshold (MNT) testing. Rescue analgesia consisted of systemic opioids. Data were analysed using Kruskal-Wallis, Mann-Whitney, Friedman or chi-square tests as appropriate. RESULTS: Intra-operatively, group PRE had lower HR and MAP at several CSEs than groups POST/CON and required less propofol [0 mg kg(-1) (0-0 mg kg(-1))] than group POST/CON [0.3 mg kg(-1) (0-0.6 mg kg(-1))]. Post-operatively, group POST had significantly higher peri-articular MNTs than groups PRE and CON up to 4 hours after recovery. No treatment effect was detected for MPS, lameness scores and rescue analgesic consumption at any time point. CONCLUSIONS AND CLINICAL RELEVANCE: Pre-operative intra-articular bupivacaine provided notable intra-operative analgesia in goats undergoing stifle arthrotomy but did not reduce post-operative pain. Post-operative intra-articular bupivacaine provided a short lasting reduction of peri-articular hyperalgesia without affecting the requirements for systemic analgesia. Multimodal perioperative pain therapy is recommended to provide adequate analgesia for stifle arthrotomy in goats.

Intra-articular calcium phosphate cement: Its fate and impact on joint tissues in a rabbit model

Clinical application of injectable ceramic cement in comminuted fractures revealed penetration of the viscous paste into the joint space. Not much is known on the fate of this cement and its influence on articular tissues. The purpose of this experimental study was to assess these unknown alterations of joint tissues after intra-articular injection of cement in a rabbit knee. Observation periods were from 1 week up to 24 months, with three rabbits per group. Norian SRS cement was injected into one knee joint, the contralateral side receiving the same volume of Ringers' solution. Light microscopic evaluation of histologic sections was performed, investigating the appearance of the cement, inflammatory reactions, and degenerative changes of the articular surface. No signs of pronounced acute or chronic inflammation were visible. The injected cement was mainly found as a single particle, anterior to the cruciate ligaments. It became surrounded by synovial tissues within 4 weeks and showed signs of superficial resorption. In some specimens, bone formation was seen around the cement. Degeneration of the articular surface showed no differences between experimental and control side, and no changes over time became apparent. No major degenerative changes were induced by the injected cement. The prolonged presence of cement still seems to make it advisable to remove radiologically visible amounts from the joint space.