Intra-articular morphine and/or bupivacaine after total knee replacement.
(17/3950)
The postoperative analgesic effects of intra-articular injections of bupivacaine and/or morphine were examined prospectively in 437 patients who had total knee replacement for osteoarthritis. They were divided randomly into four groups. Group I received 10 mg of morphine (1 ml) and 9 ml of saline, group II received 10 ml of bupivacaine (2.5 mg/ml), group III received 10 ml of saline, and group IV received 10 mg of morphine (1 ml) and 9 ml of bupivacaine (2.5 mg/ml). All analgesics administered in the first 24 hours after operation were recorded. The patients rated their pain on the McGill-Melzack scale at 1, 6, 12 and 24 hours. No significant differences were found between any of the groups in the use of Demoral and/or Toradol in 24 hours, the length of stay in hospital or the pain rating at 1, 6, 12 or 24 hours. Patients in groups I and IV, whose injections included morphine, used significantly more morphine in the first 24 postoperative hours than did groups II or III. (+info)
Intracapsular components do not change hip proprioception.
(18/3950)
We compared joint proprioception in 12 hips in 12 patients with hemiarthroplasty after fracture of the hip, in 12 hips in 11 patients with total hip arthroplasty because of osteoarthritis and in a control group of 12 age-matched patients with no clinical complaints. There was no significant difference (p = 0.05) in joint proprioception in any of the groups. There was no decrease in joint proprioception in the group with total hip arthroplasty compared with the hemiarthroplasty group or with the control group. Other factors such as stretch receptors in the adjacent tendons and muscles may have a greater influence on proprioception in the hip than the intracapsular components. (+info)
Specific targeting of activated endothelium in rat adjuvant arthritis with a 99mTc-radiolabeled E-selectin-binding peptide.
(19/3950)
OBJECTIVE: To determine the potential of an E-selectin-binding peptide (ESbp) to specifically bind activated endothelium in rheumatoid arthritis (RA) animal models. METHODS: ESbp (KYDGDITWDQLWDLMK; 2,027 daltons) was labeled with biotin and 99mTc. The affinity of ESbp derivatives for E-selectin was measured by enzyme-linked immunosorbent assay. The binding of biotin-ESbp was compared with that of an anti-E-selectin antibody, by immunohistochemical analyses of human synovial sections and sections from the Mycoplasma pulmonis MRL-lpr/lpr mouse arthritis model. 99mTc-ESbp was sequentially imaged in vivo with a gamma camera in the rat adjuvant-induced arthritis model. RESULTS: E-selectin expression was detected in human RA synovium and mouse arthritic synovium using biotin-ESbp. Both biotin-ESbp and 99mTc-labeled ESbp had high affinity for E-selectin (dissociation constant 2-5 nM). In vivo imaging showed specific binding of 99mTc-ESbp to the rat ankle joint prior to clinical manifestations of inflammation. CONCLUSION: These results demonstrate that activated endothelium can be targeted with 99mTc-ESbp. The specificity of targeting can be used to evaluate up-regulation of E-selectin in RA models, and to follow changes in this up-regulation during treatment trials. (+info)
Expression of the activation antigen CD97 and its ligand CD55 in rheumatoid synovial tissue.
(20/3950)
OBJECTIVE: Fibroblast-like synoviocytes (FLS) express decay-accelerating factor (CD55) at high levels. Recently, it was found that CD55 is a specific cellular ligand for the 7-span transmembrane receptor CD97. The objective of this study was to define the expression of this receptor-ligand pair in synovial tissue (ST) to provide more insight into the interaction between FLS and surrounding cells. METHODS: Antibodies against CD97 and CD55 were used for immunohistologic analysis of synovial biopsy specimens from 16 patients with rheumatoid arthritis (RA) and 15 patients with osteoarthritis (OA). In addition, an enzyme-linked immunosorbent assay system was used to determine the expression of soluble CD97 (sCD97) in synovial fluid (SF) from 30 patients with RA, 13 with OA, and 10 with reactive arthritis (ReA). RESULTS: In both RA and OA ST sections, strong expression of CD55 was confirmed on FLS in the intimal lining layer, where it was also found that all macrophages expressed CD97. The percentage of macrophages that expressed CD97 was lower in the synovial sublining (P = 0.005). The mean levels of sCD97 in SF were significantly higher in RA patients than in patients with OA or ReA (P < 0.0001). CONCLUSION: These results suggest that FLS are able to interact with macrophages via the CD97/CD55 receptor-ligand system. In this respect, the CD97/CD55 pair may account for the specific architecture of the intimal lining layer and may be of primary importance in maintaining and amplifying synovial inflammation. The specific increase in sCD97 levels in RA SF might be related to the presence of activated proteolytic systems or to the increase in synovial mass, rather than a consequence of local receptor-ligand interaction. (+info)
Inhibition of tumor necrosis factor alpha-induced prostaglandin E2 production by the antiinflammatory cytokines interleukin-4, interleukin-10, and interleukin-13 in osteoarthritic synovial fibroblasts: distinct targeting in the signaling pathways.
(21/3950)
OBJECTIVE: To investigate the effects of the antiinflammatory cytokines interleukin-4 (IL-4), IL-10, and IL-13 on tumor necrosis factor alpha (TNFalpha)-induced prostaglandin E2 (PGE2) release in the cellular signaling cascade on human osteoarthritis (OA) synovial fibroblasts. METHODS: Human OA synovial fibroblasts were cultured to explore the impact of IL-4, IL-10, and IL-13 on TNFalpha binding to TNF receptors (TNFR), soluble TNFR (sTNFR), cytoplasmic phospholipase A2 (cPLA2), and cyclooxygenase-2 (COX-2) production, and on the binding activity of the transcription factors nuclear factor kappaB (NF-kappaB), CCAAT-enhancer binding protein (C/EBP), activator protein 2 (AP-2), and cyclic AMP response element-binding protein (CREB). RESULTS: IL-4, IL-10, and IL-13 at 5 ng/ml dramatically reduced TNFalpha-induced PGE2 release by approximately 90% (P < 0.0001). IL-4 up-regulated the level of TNFalpha-induced TNFR by 47% (P < 0.06), while IL-10 down-regulated it by 71% (P < 0.02); IL-13 had no effect. Although statistical significance was not reached, all 3 cytokines up-regulated the basal level of sTNFR-55. IL-4 and IL-10, while not altering the basal level of sTNFR-75, significantly increased the TNFalpha-stimulated release of sTNFR-75. IL-4, IL-10, and IL-13 reduced the TNFalpha-induced COX-2 level, and IL-4 and IL-10 reduced the cPLA2 level. IL-4 had no effect on TNFalpha up-regulation of NF-kappaB, and a slight decrease was noted with IL-10 and IL-13 at the highest concentration used (5 ng/ml). IL-4 and IL-13 decreased the TNFa-induced C/EBP accumulation in a dose-dependent manner, while IL-10 up-regulated its basal level. AP-2 and CREB were not induced by TNFalpha. CONCLUSION: The results indicate that these antiinflammatory cytokines reversed the TNFalpha-induced release of PGE2 by OA synovial fibroblasts, by acting at various levels of the TNFa-dependent signaling cascade. These data shed new light on the mechanisms by which these cytokines reduce inflammatory processes. (+info)
Differential patterns of response to doxycycline and transforming growth factor beta1 in the down-regulation of collagenases in osteoarthritic and normal human chondrocytes.
(22/3950)
OBJECTIVE: To investigate the ability of doxycycline, transforming growth factor beta1 (TGFbeta1), and phorbol myristate acetate (PMA) to modulate collagenase synthesis in osteoarthritic (OA) chondrocytes. METHODS: Levels of fibroblast collagenase (matrix metalloproteinase 1 [MMP-1]), neutrophil collagenase (MMP-8), and collagenase 3 (MMP-13) proteins and messenger RNA (mRNA) were measured in chondrocytes isolated from involved and uninvolved areas of OA cartilage and from normal human chondrocytes, after treatment with doxycycline, TGFbeta1, and PMA. RESULTS: Chondrocytes isolated from cartilage immediately adjacent to the OA lesion had, on average, 1.8-3.9-fold higher basal levels of MMP mRNA. These cells down-regulated collagenase proteins and mRNA upon incubation with TGFbeta1. In contrast, chondrocytes from areas located more distant from the macroscopic lesion increased MMP-13 mRNA, while MMP-1 and MMP-8 decreased after stimulation with TGFbeta1. Discoordinate regulation was observed after stimulation with PMA, with an increase in MMP-1 and MMP-8 but a decrease in MMP-13. Incubation of OA chondrocytes with doxycycline (1-10 microg/ml), at pharmacologically achievable levels, decreased levels of mRNA of all 3 collagenases, but not G3PDH. In addition, doxycycline inhibited the increase in mRNA for these enzymes in normal chondrocytes stimulated with tumor necrosis factor alpha. CONCLUSION: These findings suggest that regulation of MMP-1, MMP-8, and MMP-13 in OA chondrocytes, although mediated by differing pathways, can be decreased by treatment with doxycycline at low concentrations. Our data provide a rationale for the use of doxycycline in the treatment of OA. (+info)
Beyond disability: measuring the social and personal consequences of osteoarthritis.
(23/3950)
OBJECTIVE: Measuring the impact of osteoarthritis has traditionally focused on the disease (measures of impairment), functional disability and latterly, general health status or quality of life. This paper highlights the importance of measuring the wider personal and social consequences of OA both at a population and an individual patient level. DESIGN: The World Health Organisation definition of handicap is used to describe this wider impact of disease and measures of handicap, both generic and disease-specific are reviewed. The measurement of handicap in OA is illustrated by the use of the Disease Repercussion Profile in a clinical trial of orthopaedic out-patients with OA and low back pain. These data are compared to routine clinical handicap data collected on consecutive patients with rheumatoid arthritis attending a different outpatient clinic. RESULTS: OA patients reported handicap in six areas of their lives: functional and social activities, relationships, socio-economic status, emotional well-being and body image. The prevalence was similar to that reported by RA patients. OA patients reported more severe handicap than RA patients in each of the 6 areas (F ratios 4. 97-55.67) and the differences were statistically significant (P values 0.03-0.0001) for all dimensions except functional and social handicap. The LBP patients scored slightly more severe handicap on all dimensions than the OA patients but these differences did not reach statistical significance. However, they scored significantly more severe handicap than the RA patients (F ratios 8.49-174.72, P< 0.0001). CONCLUSIONS: These data suggest that the psychosocial impact of OA may have been underestimated and highlight the importance of going beyond disability in assessing the impact of OA. Measurement of the wider impact of OA can be achieved using disease-specific and generic measures of handicap. The choice of tool will depend upon the setting (research or clinical practice) and the purpose of measurement. (+info)
The role of joint innervation in the pathogenesis of arthritis.
(24/3950)
Recently, an expanding body of knowledge has documented the nature and functions of receptors in joint tissues and their potential importance in preserving the smooth normal functioning of the motor-skeletal system and in amplifying the inflammatory response to joint injuries and diseases. This review summarizes the current knowledge of the anatomical and physiological substrates of these mechanisms. The distribution, morphologic and functional characteristics of joint receptors have been well described. In the past decade there has been a new appreciation of the major role played by sensory neurons in promoting regional inflammatory responses, and many of the specific neuronal mechanisms and molecules that mediate these reflexes have been identified. This knowledge promises to significantly improve the selectivity and effectiveness of pharmacologic approaches to pain, trauma and regional inflammatory disorders. Other investigations have revealed important contributions of joint receptors to motor function. These refer not to proprioception or the sense of limb position in space, but rather to a more sophisticated tailoring of muscle activity to increase joint stability and to protect joint structures from damaging loads. Whether a loss of these reflexes may play a role in the pathogenesis of osteoarthritis remains controversial. However, there is a growing consensus that a loss of these reflexes may contribute to the morbidity associated with disruption of the anterior cruciate ligament. Synovial joints are sites of major interactions between the musculoskeletal and the nervous systems. Understanding the mechanisms that activate and control these interactions will certainly offer the opportunity to develop new, more effective treatments for patients with joint disorders. (+info)