Pere Benito

In Vivo Evaluation of 3-Dimensional Polycaprolactone Scaffolds for Cartilage Repair in Rabbits

Background Cartilage tissue engineering using synthetic scaffolds allows maintaining mechanical integrity and withstanding stress loads in the body, as well as providing a temporary substrate to which transplanted cells can adhere. Purpose This study evaluates the use of polycaprolactone (PCL) scaffolds for the regeneration of articular cartilage in a rabbit model. Study Design Controlled laboratory study. Methods Five conditions were tested to attempt cartilage repair. To compare spontaneous healing (from subchondral plate bleeding) and healing due to tissue engineering, the experiment considered the use of osteochondral defects (to allow blood flow into the defect site) alone or filled with bare PCL scaffold and the use of PCL-chondrocytes constructs in chondral defects. For the latter condition, 1 series of PCL scaffolds was seeded in vitro with rabbit chondrocytes for 7 days and the cell/scaffold constructs were transplanted into rabbits’ articular defects, avoiding compromising the subchondral bone. Cell pellets and bare scaffolds were implanted as controls in a chondral defect. Results After 3 months with PCL scaffolds or cells/PCL constructs, defects were filled with white cartilaginous tissue; integration into the surrounding native cartilage was much better than control (cell pellet). The engineered constructs showed histologically good integration to the subchondral bone and surrounding cartilage with accumulation of extracellular matrix including type II collagen and glycosaminoglycan. The elastic modulus measured in the zone of the defect with the PCL/cells constructs was very similar to that of native cartilage, while that of the pellet-repaired cartilage was much smaller than native cartilage. Conclusion The results are quite promising with respect to the use of PCL scaffolds as aids for the regeneration of articular cartilage using tissue engineering techniques.

Documento de consenso sobre el diagnóstico y tratamiento de la fibromialgia en Cataluña

La fibromialgia (FM) es una enfermedad cronica y compleja que provoca dolores extensos que pueden llegar a ser invalidantes, y afecta a la esfera biologica, psicologica y social del paciente. La FM es un problema de salud dada su elevada prevalencia y morbilidad, su alto indice de frecuentacion y el elevado consumo de recursos sanitarios que provoca 1 . El Pla de Salut de Catalunya 1996-1998 ya recoge este problema, fruto del cual se elaboraron unos Criterios Comunes Minimos para la Atencion de Enfermos con Fibromialgia. Debido a la evolucion de los conocimientos que ha acontecido en los ultimos anos y a la confirmacion de su alta prevalencia y morbilidad, se ha constituido un grupo de trabajo multidisciplinario con la voluntad de redactar un documento orientativo, a modo de guia de practica clinica, que estructure y homogeneice los conceptos y actitudes que se pueden aplicar a estos pacientes.

Decreased metalloproteinase production as a response to mechanical pressure in human cartilage: a mechanism for homeostatic regulation

Articular cartilage is optimised for bearing mechanical loads. Chondrocytes are the only cells present in mature cartilage and are responsible for the synthesis and integrity of the extracellular matrix. Appropriate joint loads stimulate chondrocytes to maintain healthy cartilage with a concrete protein composition according to loading demands. In contrast, inappropriate loads alter the composition of cartilage, leading to osteoarthritis (OA). Matrix metalloproteinases (MMPs) are involved in degradation of cartilage matrix components and have been implicated in OA, but their role in loading response is unclear. With this study, we aimed to elucidate the role of MMP-1 and MMP-3 in cartilage composition in response to mechanical load and to analyse the differences in aggrecan and type II collagen content in articular cartilage from maximum- and minimum-weight-bearing regions of human healthy and OA hips. In parallel, we analyse the apoptosis of chondrocytes in maximal and minimal load areas. Because human femoral heads are subjected to different loads at defined sites, both areas were obtained from the same hip and subsequently evaluated for differences in aggrecan, type II collagen, MMP-1, and MMP-3 content (enzyme-linked immunosorbent assay) and gene expression (real-time polymerase chain reaction) and for chondrocyte apoptosis (flow cytometry, bcl-2 Western blot, and mitochondrial membrane potential analysis). The results showed that the load reduced the MMP-1 and MMP-3 synthesis (p < 0.05) in healthy but not in OA cartilage. No significant differences between pressure areas were found for aggrecan and type II collagen gene expression levels. However, a trend toward significance, in the aggrecan/collagen II ratio, was found for healthy hips (p = 0.057) upon comparison of pressure areas (loaded areas > non-loaded areas). Moreover, compared with normal cartilage, OA cartilage showed a 10- to 20-fold lower ratio of aggrecan to type II collagen, suggesting that the balance between the major structural proteins is crucial to the integrity and function of the tissue. Alternatively, no differences in apoptosis levels between loading areas were found – evidence that mechanical load regulates cartilage matrix composition but does not affect chondrocyte viability. The results suggest that MMPs play a key role in regulating the balance of structural proteins of the articular cartilage matrix according to local mechanical demands.

Comparative efficacy of intra-articular hyaluronic acid and corticoid injections in osteoarthritis of the first carpometacarpal joint: results of a 6-month single-masked randomized study.

OBJECTIVE The study aim was to compare the efficacy and safety of ultrasound-guided intra-articular injections of hyaluronic acid and betamethasone in the management of patients with osteoarthritis of the thumb. METHODS Eighty-eight evaluable patients diagnosed with osteoarthritis of the thumb (Kellgren-Lawrence grade II-III) received ultrasound-guided intra-articular treatment with hyaluronic acid (48) or betamethasone (40). In total, 3 local injections were scheduled at 7-day intervals. Assessments were performed at baseline and at 7, 14, 30, 90, and 180 days. RESULTS In both study groups, the pain Visual Analogue Scale and Functional Index for Hand Osteoarthritis scores decreased significantly during follow-up compared to baseline. There were no significant differences between the groups. However, at 90 days, the functional score showed a trend towards greater clinical improvement in the hyaluronic acid group (P 0.071). A subanalysis of patients with Functional Index score≥5 and Visual Analogue Scale score≥3 at baseline showed a significantly higher median functionality score in the hyaluronic acid group (P 0.005 at 90 days and P 0.020 at 180 days). Further limiting analysis to a baseline pain score≥5 showed significantly greater improvement in functionality score (P 0.004 at 180 days), which was already apparent after the second intra-articular injection at 14 days (P 0.028). In this patient subset, the mean pain score also improved significantly at 180 days (P 0.02). CONCLUSIONS Both hyaluronic acid and betamethasone were effective and well-tolerated for the management of rhizarthrosis. Hyaluronic acid was more effective over time and more efficiently improved functionality and pain in patients with more severe symptoms.

Ease of ventilation through the cuffed oropharyngeal airway (COPA), the laryngeal mask airway and the face mask in a cardiopulmonary resuscitation training manikin.

The aim of this study was to compare ease of ventilation of a cardiopulmonary resuscitation manikin using a cuffed oropharyngeal airway (COPA), a laryngeal mask airway (LMA) and a face mask, by two groups of people with different levels of earlier experience in cardiopulmonary resuscitation (CPR). Enrolled were, 108 people identified as experienced (54), or inexperienced (54), in CPR. Training equipment included a manikin, a COPA (n=10), an LMA (n=4), a face mask (n=4) and self-inflating bag-valve device. The same investigator explained the theoretical use and practice of the three techniques with the subjects in groups of three. The variables recorded were the number of attempts needed to achieve correct placement (and a tidal volume of 200 ml, was achieved), the insertion time for the COPA and the LMA, and the average time taken to achieve the first ten correct ventilations. The face mask and LMA required fewer attempts for correct placement than did the COPA. The LMA also took less time to insert than the COPA. The face mask required a significantly shorter total time with all attempts and the mean time of placement and time to achieve ten correct ventilations was shorter than with either the LMA or the COPA (P=0.0001). We conclude that the face mask offers an easier and quicker way to provide ventilation for CPR manikins than does the COPA or the LMA. Earlier experience affects the ease of insertion of the LMA and the total time needed to achieve effective ventilation.

Characterization of opticin digestion by proteases involved in osteoarthritis development.

OBJECTIVE Opticin is a class III member of the small leucine-rich repeat proteoglycan (SLRP) family, produced in articular joint tissues. In normal and osteoarthritic (OA) cartilage, opticin is degraded. This study aimed to assess whether human cartilage opticin is degraded by the main proteases involved in OA pathophysiology, and to determine the protease cleavage sites of this SLRP. METHODS We analyzed the proteolytic activity of matrix metalloproteinases (MMPs)-1, -2, -3, -7, -8 and -9, and ADAMTS-4 and -5 on proteoglycan extracts from normal and moderately fibrillated OA human cartilage, and on recombinant human opticin. Opticin degradation was analyzed by Western blotting and cleavage sites were determined by sequence analysis. RESULTS All eight proteases digested opticin from proteoglycan extracts from both normal and OA samples, as well as recombinant human opticin, MMP-2 and MMP-7 are the proteases that degrade recombinant human opticin most efficiently. The opticin cleavage site determined for these MMPs was between the glycosylation and leucine-rich repeat domains. MMP-7 had two additional digestion sites near the N-terminal end of opticin. CONCLUSION Opticin is a substrate for several MMPs and aggrecanases involved during OA cartilage degradation, and seems to be a preferential substrate for MMP-7. The role of opticin in cartilage degeneration could be related to decreased levels of intact opticin, followed by its proteolytic degradation, which in turn may stimulate some of the modifications observed in the OA cartilage, such as neovascularisation and changes in the extracellular matrix.

Osteonecrosis vertebral y vertebroplastia percutánea

La osteonecrosis vertebral se caracteriza por presentar el fenomeno de vacio intravertebral. Es un proceso poco frecuente y aunque puede ser debido a diferentes afecciones, la causa mas frecuente es la postraumatica. La explicacion de que aparezca gas intravertebral no es del todo conocida. Presentamos el caso de una paciente de 74 anos que despues de sufrir un traumatismo vertebral inicio clinica de dolor dorsolumbar intenso. El estudio radiologico simple, la tomografia computarizada y la resonancia magnetica confirmaron el fenomeno del vacio intravertebral. Hemos hecho una revision de este signo radiologico y comentamos la evolucion despues de vertebroplastia percutanea.Vertebral osteonecrosis is characterized by the presence of the intravertebral vacuum phenomenon. It is a relatively uncommon disease and although it may be caused by different pathologies, the most frequent cause is posttraumatic. The explanation for the presence of intravertebral gas is not known completely. We present the case of a 74-year-old patient who after suffering a vertebral traumatism, to complain of intense vertebral pain. A simple radiological study, CT scan, and magnetic resonance confirmed the presence of intravertebral vacuum phenomenon. We studied this radiological sign and then commented on its evolution after percutaneous vertebroplasty.

Eficacia de la gabapentina en el tratamiento del síndrome del túnel carpiano

BACKGROUND AND OBJECTIVE: To evaluate the analgesic efficacy and safety of gabapentin in the treatment of carpal tunnel syndrome (CTS), as well as the electromyographic (EMG) evolution after 6 months. PATIENTS AND METHOD: A prospective study with a 6-month follow-up of patients with EMG diagnosis of primary CTS starting treatment with 1.800 mg/day of gabapentin. At baseline visit and after 6 months of treatment a complete clinical evaluation and an EMG study were performed. Adverse effects of gabapentin were also registered. RESULTS: Twenty-five patients were included, mean age (standard deviation) 58.88 (7.69) years. After 6 months of treatment, a statistically significant reduction of pain (p = 0.001) and improvement of severity of symptoms (p = 0.008) were observed, although functional capacity did not change. EMG was performed in 19 patients at 6 months. Compared to baseline EMG: 52.6% patients showed no changes in EMG findings, while 5.3% patients showed improvement and in 26.3% the EMG was normal. Progression was only seen in 15.8% of patients after 6 months of treatment. In 28% of the patients gabapentin was stopped because of side effects. CONCLUSIONS: In our series, gabapentin was effective in the reduction of pain and improvement of the severity of the symptoms. Results of EMG after 6 months of treatment showed no changes, with improvement and/or remission in 84.2% of the cases. The drug was safe and well tolerated.

Brain imaging of pain sensitization in patients with knee osteoarthritis

Abstract A relevant aspect in osteoarthritic pain is neural sensitization. This phenomenon involves augmented responsiveness to painful stimulation and may entail a clinically worse prognosis. We used functional magnetic resonance imaging (fMRI) to study pain sensitization in patients with knee osteoarthritis. Sixty patients were recruited and pain sensitization was clinically defined on the basis of regional spreading of pain (spreading sensitization) and increased pain response to repeated stimulation (temporal summation). Functional magnetic resonance imaging testing involved assessing brain responses to both pressure and heat stimulation. Thirty-three patients (55%) showed regional pain spreading (simple sensitization) and 19 patients (32%) showed both regional spreading and temporal summation. Sensitized patients were more commonly women. Direct painful pressure stimulation of the joint (articular interline) robustly activated all of the neural elements typically involved in pain perception, but did not differentiate sensitized and nonsensitized patients. Painful pressure stimulation on the anterior tibial surface (sensitized site) evoked greater activation in sensitized patients in regions typically involved in pain and also beyond these regions, extending to the auditory, visual, and ventral sensorimotor cortices. Painful heat stimulation of the volar forearm did not discriminate the sensitization phenomenon. Results confirm the high prevalence of pain sensitization secondary to knee osteoarthritis. Relevantly, the sensitization phenomenon was associated with neural changes extending beyond strict pain-processing regions with enhancement of activity in general sensory, nonnociceptive brain areas. This effect is in contrast to the changes previously identified in primary pain sensitization in fibromyalgia patients presenting with a weakening of the general sensory integration.

Economic evaluation of tramadol/paracetamol in the management of pain in patients with osteoarthritis in Spain

Abstract Objective To compare the costs of treating osteoarthritis (OA) pain using combination tramadol/paracetamol tablets, Non-Steroidal Anti-Inflammatory Agents (NSAID) alone or NSAID plus proton pump inhibitors (PPI) from the perspective of the Spanish National Health System. Methods A decision-analytical model was constructed to analyze the cost associated with three treatment strategies over 6 months. A cost-minimization approach was used, which considered data related to resource use, medication costs and costs for the treatment of adverse events. Results In the base-case analysis, costs for 6 months of treatment of OA pain using tramadol/paracetamol were €232.86, compared with €274.60 for NSAID + PPI and €133.75 for NSAID alone. This provided a savings of €41.74 per patient over 6 months for tramadol/paracetamol compared with NSAID + PPI and a cost increase of €99.11 compared with NSAID alone. When renal adverse events associated with NSAID were considered, tramadol/paracetamol was cost saving compared with all NSAID-based regimens (saving €140.02 vs NSAID alone, €280.86 vs NSAID + PPI). Conclusion Based on the results of a theoretical decision-analytic model, the data obtained may suggest that tramadol/paracetamol is cost saving compared with NSAID + PPI for the treatment of OA pain over a period of 6 months. Tramadol/paracetamol is also cost saving compared with treatment with NSAID alone if considering renal adverse events