Synovitis of small joints: sonographic guided diagnostic and therapeutic approach.
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OBJECTIVE: The aim of this pictorial essay is to describe the sonographic guided approach to investigation and local injection therapy of a small joint in a patient with psoriatic arthritis (PA). METHODS: Sonographic pictures are obtained using a high frequency ultrasonography apparatus equipped with a 13-MHz transducer. RESULTS: Ultrasonography allows a careful morphostructural assessment of soft tissue involvement in PA patients. Sonographic findings include joint cavity widening, capsular thickening, synovial proliferation, synovial fluid changes, tendon sheath widening. Ultrasound guided placement of the needle within the joint and injection of corticosteroid under sonographic control can be easily performed. CONCLUSIONS: High frequency ultrasonography is a quick and safe procedure that allows a useful diagnostic and therapeutic approach in patients with arthritis of small joints. (+info)
Placement of intra-articular injections verified by mini air-arthrography.
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OBJECTIVE: To develop and assess a simple, inexpensive method for ascertaining the placement of intra-articular injections for knee osteoarthritis METHODS: During a one year period patients with "dry" osteoarthritis of the knee who received intra-articular therapy were tested by air-arthrography. Along with triamcinolone and lignocaine (lidocaine), 5 ml of air was injected into the joint. On subsequent lateral and anterior-posterior radiographs a correct placement was verified by a sharply defined shadow of air in the suprapatellar pouch, while extra-articular air was diffusely spread in the surrounding tissue. RESULTS: In 51 of 56 cases the injection was correctly placed. In the remaining five cases the injection was immediately repeated and positioned within the joint. No adverse events were seen that could be ascribed to the use of air during the study, although bleeding in the quadriceps was seen one week after an extra-articular injection. CONCLUSION: With mini-air arthrography, it is possible to test the placement of intra-articular injections in knee joints. The method is proposed as a learning tool as well as providing a means of quality assurance in studies involving intra-articular injections. (+info)
Adenoviral vector-mediated overexpression of IL-4 in the knee joint of mice with collagen-induced arthritis prevents cartilage destruction.
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Rheumatoid arthritis is a chronic inflammatory joint disease, leading to cartilage and bone destruction. In this study, we investigated the effects of local IL-4 application, introduced by a recombinant human type 5 adenovirus vector, in the knee joint of mice with collagen-induced arthritis. One intraarticular injection with an IL-4-expressing virus caused overexpression of IL-4 in the mouse knee joint. Enhanced onset and aggravation of the synovial inflammation were found in the IL-4 group. However, despite ongoing inflammation, histologic analysis showed impressive prevention of chondrocyte death and cartilage erosion. In line with this, chondrocyte proteoglycan synthesis was enhanced in the articular cartilage. This was quantified with ex vivo 35S-sulfate incorporation in patellar cartilage and confirmed by autoradiography on whole knee joint sections. Reduction of cartilage erosion was further substantiated by lack of expression of the stromelysin-dependent cartilage proteoglycan breakdown neoepitope VDIPEN in the Ad5E1 mIL-4-treated knee joint. Reduced metalloproteinase activity was also supported by markedly diminished mRNA expression of stromelysin-3 in the synovial tissue. Histologic analysis revealed marked reduction of polymorphonuclear cells in the synovial joint space in the IL-4-treated joints. This was confirmed by immunolocalization studies on knee joint sections using NIMP-R14 staining and diminished mRNA expression of macrophage-inflammatory protein-2 in the synovium tissue. mRNA levels of TNF-alpha and IL-1beta were suppressed as well, and IL-1beta and nitric oxide production by arthritic synovial tissue were strongly reduced. Our data show an impressive cartilage-protective effect of local IL-4 and underline the feasibility of local gene therapy with this cytokine in arthritis. (+info)
Evidence for neurogenic transmission inducing degenerative cartilage damage distant from local inflammation.
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OBJECTIVE: To investigate involvement of the nervous system in ipsilateral and contralateral joint inflammation. METHODS: Freund's complete adjuvant (CFA; 1 mg or 1 microg) was injected unilaterally and the messages (a) from the hind paw to the ipsilateral and contralateral knees and (b) from one knee to the contralateral knee were analyzed. The degenerative impact of the local injury on distant cartilage was assessed using patellar proteoglycan synthesis as an indicator. Neurogenic mechanisms were blocked either by spinal cord compression or by injection of neurokinin 1 (NK-1) antagonist, or they were mimicked by intraarticular injection of substance P. The data were compared with those gathered in a model of systemic inflammation, characterized by fever and serum interleukin-6 production. RESULTS: After unilateral subcutaneous injection of CFA, proteoglycan anabolism decreased bilaterally. Spinal cord compression and administration of the NK-1 antagonist inhibited the response in the contralateral limb. Following 1 mg CFA subcutaneous injection, the ipsilateral response implicated both neurogenic and systemic mechanisms, whereas the nervous system alone was implicated after 1 microg subcutaneous CFA injection. The 1 microg CFA intraarticular injection induced a degenerative contralateral signal, which was abolished by spinal cord compression and by pretreatment with the NK-1 antagonist. Intraarticular injection of 1 microg CFA also induced an ipsilateral increase of anabolism, which was enhanced by spinal cord compression. Similar results were obtained after intraarticular injections of substance P. These effects were not reproduced with turpentine treatment, a systemic model, in which spinal cord compression had no effect. CONCLUSION: A unilateral inflammation can induce, by neurogenic mechanisms, distal bilateral degeneration of articular cartilage, implicating involvement of neuropeptides. (+info)
Intra-articular delivery of a herpes simplex virus IL-1Ra gene vector reduces inflammation in a rabbit model of arthritis.
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To evaluate the use of HSV-based vectors for arthritis gene therapy we have constructed a first-generation, ICP4 deficient, replication defective herpes simplex virus (HSV) vector (S/0-) and a second-generation HSV vector derivative (T/0-) deficient for the immediate-early genes ICP4, 22 and 27, each carrying a soluble TNF receptor or IL-1 receptor antagonist transgene cassette. A rabbit synovial-fibroblast line in culture, infected by either vector enabled high-level expression of the transgene product. However, following a single intra-articular injection of the vectors into rabbit knee joints, only the second-generation, HSV T/0- vector expressed detectable levels of soluble TNFR in synovial fluid. Synovial lavage fluid from inoculated joints con- tained up to 12 ng/ml of soluble receptor that persisted at detectable, but reduced levels for at least 7 days. When tested in an experimental model of arthritis generated by intra-articular overexpression of interleukin-1beta using retrovirus transduced synovial cells, the HSV T/0- vector expressing the interleukin-1 receptor antagonist was found to inhibit leukocytosis and synovitis significantly. The improved levels and duration of intra-articular transgene expression achieved via HSV-mediated gene delivery suggest that an HSV vector system could be used for therapeutic applications in patients with rheumatoid arthritis (RA) and other joint-related inflammatory diseases. (+info)
BACKGROUND: Spontaneous tremor is relatively common in normothermic patients after operation and has been attributed to many causes. The hypothesis that nonthermoregulatory shivering-like tremor is facilitated by postoperative pain was tested. In addition, the effects of intravenous lidocaine on nonthermoregulatory tremor were evaluated. METHODS: Patients undergoing knee surgery were anesthetized with 2 microg/kg intravenous fentanyl and 0.2 mg/kg etomidate. Anesthesia was maintained with 1.7 +/- 0.8% (mean +/- SD) isoflurane. Intraoperative forced-air heating maintained normothermia The initial 44 patients were randomly allocated to receive an intra-articular injection of 20 ml saline (n = 23) or lidocaine, 1.5% (n = 21). The subsequent 30 patients were randomly allocated to receive an intravenous bolus of 250 microg/kg lidocaine followed by an infusion of 13 microg x kg(-1) x h(-1) lidocaine or an equivalent volume of saline when shivering was observed. Patient-controlled analgesia was provided for all patients: 3.5 mg piritramide, with a lockout interval of 5 min, for an unlimited total dose. Shivering was graded by a blinded investigator using a four-point scale. Pain was assessed by a 100-mm visual analog scale (0 = no pain and 100 = worst pain). The arteriovenous shunt status was evaluated with forearm-minus-fingertip skin-temperature gradients. RESULTS: Morphometric characteristics and hemodynamic responses were similar in the four groups. Core and mean skin temperature remained constant or increased slightly compared with preoperative values, and postoperative skin-temperature gradients were negative (indicating vasodilation) in nearly all patients. After intra-articular injection of saline, pain scores for the first postoperative hour averaged 46 +/- 32 mm (mean +/- SD), and 10 of the 23 (43%) patients shivered. In contrast, the pain scores of patients who received intra-articular lidocaine were significantly reduced to 5 +/- 9 mm and shivering was absent in this group (P < 0.05). In the second portion of the study, neither intravenous lidocaine nor saline reduced the magnitude or duration of nonthermoregulatory tremor or the patients' pain scores. CONCLUSIONS: Intra-articular, but not intravenous, lidocaine reduced surgical pain and prevented nonthermoregulatory shivering. Therefore, these data indicate that postoperative pain facilitates nonthermoregulatory shivering. (+info)
Persistence of mild, early inflammatory arthritis: the importance of disease duration, rheumatoid factor, and the shared epitope.
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OBJECTIVE: To determine the factors that predict clinical outcome at 6 months for patients with mild, early inflammatory arthritis. METHODS: Sixty-three patients with mild, untreated, early arthritis were given a single dose of corticosteroids at presentation. Administration was intramuscular if disease was polyarticular (n = 53) or intraarticular if patients had <5 synovitic joints (n = 10). The primary outcome measure was clinical disease remission or persistence of arthritis at 6 months following injection. RESULTS: At 6 months following injection, 49 of the 63 patients (78%) had persistent inflammatory joint disease. The other 14 (22%) had clinical disease remission. Regression analysis showed that only disease duration was significantly associated with persistent arthritis (P < 0.05). The other significant factor (by chi-square test) was the presence of the shared epitope (SE). Of the patients fulfilling the American College of Rheumatology (ACR) criteria at presentation (51% of the total), 53% with disease duration of < or = 12 weeks at presentation had persistent disease 6 months later, compared with 94% of those who presented with disease duration of >12 weeks. CONCLUSION: The strongest predictor of persistent disease was a disease duration of >12 weeks. Rheumatoid factor and SE were also predictors to a lesser extent. Patients who both fulfilled the ACR classification criteria for rheumatoid arthritis (RA) and had a short disease duration included some with an excellent prognosis. Therefore, 12 weeks may be a more appropriate disease duration to use for the RA classification criteria. Administering a bolus of corticosteroids may be a useful diagnostic/therapeutic approach. (+info)
Pro-inflammatory effects of the aminobisphosphonate ibandronate in vitro and in vivo.
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OBJECTIVES: To investigate the effects of the aminobisphosphonate, ibandronate, on the course of joint inflammation in rat antigen-induced arthritis (AIA) and the release of pro-inflammatory cytokines in partially purified human peripheral blood mononuclear cells (PBMC). METHODS: Rats with AIA received a single intra-articular injection of ibandronate (1 mg) 7 days post-arthritis induction and knee swelling was measured for 7 days thereafter. The effects of ibandronate (300 microg/ml) on PBMC cytokine production and activation marker expression were determined using polymerase chain reaction (PCR)/ELISA and FACS analysis, respectively. RESULTS: Joint swelling, associated with AIA, was sustained in ibandronate-treated rats compared with saline-treated control rats. Ibandronate stimulated the production of interferon gamma (IFN-gamma) in adherent PBMC, and increased the surface expression of FcgammaRI and HLA DP, DQ, DR on the adherent monocyte population. Activation by lipopolysaccharide (LPS) of PBMC previously incubated with ibandronate led to enhanced levels of tumour necrosis factor alpha (TNF-alpha) secretion, and this could be partially inhibited by neutralizing antibodies to IFN-gamma. CONCLUSIONS: The enhanced production of TNF-alpha by ibandronate-treated PBMC in vitro involves stimulation of adherent monocytes by IFN-gamma prior to LPS-induced activation. Similar cellular interactions may be involved in the pro-inflammatory effects of ibandronate in vivo. (+info)