Dual effect of nitric oxide in articular inflammatory pain in zymosan-induced arthritis in rats.
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The contribution of nitric oxide (NO) to articular pain in arthritis induced by zymosan (1 mg, intra articular) in rats was assessed by measuring articular incapacitation (AI). Systemic treatment with the non-selective NO synthase (NOS) inhibitor L-NAME (10 - 100 mg kg(-1) i.p.) or with the selective iNOS inhibitors aminoguanidine (AG; 10 - 100 mg kg(-1) i.p.) or 1400W (0.5 - 1 mg kg(-1) s.c.) inhibited the AI induced by injection of zymosan 30 min later. Local (intra articular) treatment with the NOS inhibitors (L-NAME or AG, 0.1 - 1 micromol; 1400W, 0.01 (micromol) 30 min before zymosan also inhibited the AI. Systemic or local treatment with the NOS inhibitors (L-NAME; AG, 100 mg kg(-1) i.p. or 0.1 micromol joint(-1); 1400W, 1 mg kg(-1) s.c. or 0.01 micromol joint(-1)), 2 h after zymosan did not affect the subsequent AI. Local treatment with the NO donors SNP or SIN-1, 2 h after zymosan did inhibit AI. L-NAME and AG, given i.p. inhibited nitrite but not prostaglandin E(2) (PGE(2)) levels in the joints. L-NAME (100 mg kg(-1)) but not AG (100 mg kg(-1)) increased mean arterial blood pressure. Neither L-NAME, AG nor the NO donor SIN-1 altered articular oedema induced by zymosan. In conclusion, inhibitors of iNOS decrease pain in zymosan arthritis only when given before the zymosan. This was not due to inhibition of articular PGE(2) release or oedema. NO donors also promoted antinociception in zymosan arthritis without affecting oedema. (+info)
The efficacy and safety of intraarticular corticosteroid therapy for coxitis in juvenile rheumatoid arthritis.
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OBJECTIVE: To study the efficacy and safety of intraarticular triamcinolone hexacetonide (IATH) for the treatment of coxitis in patients with juvenile rheumatoid arthritis (JRA). METHODS: Fifty consecutive patients with JRA and coxitis were studied prospectively. Forty-eight children received IATH in 67 arthritic hips. The remaining 2 children exhibited 3 cases of femoral head necrosis (FHN) at the initial assessment and were only followed up; both were receiving long-term systemic steroids. After a minimum of 2 years, the study was concluded with a final evaluation that included magnetic resonance imaging. RESULTS: In 39 of 67 hip joints (58%), remission of the coxitis for a period of 2 years was obtained through a single administration of IATH, while another 12 hip joints showed remission of coxitis after repeated TH injections (total remission rate 76%). We observed 2 patients with FHN following IATH. Both of these children were receiving long-term systemic steroids. During the period between onset of JRA and screening assessment for this study, the children exhibited 2.4 cases of FHN per 100 patient-years, while 1.5 cases of FHN per 100 patient-years were observed between IATH treatment and final followup. All 5 observed cases of FHN occurred among the 20 children who received long-term systemic steroids, while no necrosis occurred in the 30 children who did not receive systemic corticosteroids (P = 0.009 by Fisher's exact test). CONCLUSION: IATH for juvenile rheumatoid coxitis was an effective treatment that did not increase the rate of FHN. Systemic steroids, however (or their covariable, severity of JRA), may increase the risk of FHN in JRA. (+info)
C3-Tat/HIV-regulated intraarticular human interleukin-1 receptor antagonist gene therapy results in efficient inhibition of collagen-induced arthritis superior to cytomegalovirus-regulated expression of the same transgene.
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OBJECTIVE: To achieve disease-inducible expression of recombinant antiinflammatory proteins in order to allow autoregulation of drug dose by natural homeostatic mechanisms. METHODS: We compared the inducible 2-component expression system (C3-human immunodeficiency virus/transactivator of transcription [C3-Tat/HIV]) with the constitutive cytomegalovirus (CMV) promoter in the polyarticular collagen-induced arthritis (CIA) model in mice. DBA/1 mice were immunized with bovine type II collagen and were given boosters on day 21. On day 22, mice were injected intraarticularly with the adenoviral vectors AdCMVLuc, AdCMVhIL-1Ra, AdC3-Tat/HIV-Luc, or AdC3-Tat/HIV-hIL-1Ra. The injected knee joints and hind paws were then scored for signs of arthritis, and knee joint histology was compared. RESULTS: The CMV-driven interleukin-1 receptor antagonist (IL-1Ra) expression resulted in a high constitutive expression and amelioration of CIA. C3-Tat/HIV-driven IL-1Ra expression could be detected only on days 24, 29, and 35. Fourteen days after injection of the vectors, CIA was significantly better inhibited by the C3-Tat/HIV-driven IL-1Ra expression compared with the CMV-driven IL-1Ra expression. Moreover, prevention of CIA in the knee joints also prevented CIA in the untreated hind paws. CONCLUSION: Our data demonstrate for the first time the feasibility of an inducible expression system for local production of IL-1Ra for treatment of arthritis in the CIA model. (+info)
An instructional program to facilitate teaching joint/soft-tissue injection and aspiration.
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OBJECTIVE: We developed an instructional program to teach aspiration and injection techniques of the knee and shoulder to medical students and residents. METHODS: Residents and fourth-year medical students participating in a rheumatology elective were assigned by deterministic allocation into 3 groups: the Traditional group received no specific instruction in arthrocentesis but simply rotated through rheumatology, learning injection techniques only if they saw patients who required them; the Lecture-only group received only the didactic lecture and did not have the opportunity to practice on the models; the Program group participated in the newly developed program of instruction that combined a didactic lecture and a hands-on workshop using the anatomic models to practice arthrocentesis techniques. RESULTS: The scores on the written examination for those in the Program group (mean score 37.46 out of 40 possible) and the Lecture-only group (mean 37.75) were significantly higher than those of the Traditional group (mean 33.15) (P <.05). The scores on the practical examination for those in the Program group (mean score 24.08 out of 26 possible) were significantly higher than those of the Lecture-only (mean 20.50) and Traditional (mean 17.33) (P <.05) CONCLUSION: The addition of this type of instruction to supplement a traditional internal medicine rotation can enhance a learner's ability to perform joint/soft-tissue injection and aspiration. (+info)
Four cases of a secondary Cushingoid state following local triamcinolone acetonide (Kenacort) injection.
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Intra-articular, paratendinous or other soft tissue corticosteroid injections are well-recognised treatment modalities for rheumatic conditions in which a debilitating inflammatory component persists. A corticosteroid injection that is locally administered only sporadically evokes adverse effects. We report four cases of secondary Cushingoid state, twice due to single, and twice due to repetitive triamcinolone acetonide (TCA: Kenacort) injection. A consulted general practitioner, internist and gynaecologist were not aware of the possibility that such a local injection may evoke a Cushingoid state with moon face, buffalo hump and/or disturbance of the menstrual cycle. Therefore we describe here the four cases we recently encountered. (+info)
Efficacy of intraarticular hyaluronic acid in patients with osteoarthritis--a prospective clinical trial.
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AIM: The goal of this study was to determine whether or not the intraarticular administration of hyaluronic acid can improve functional parameters, such as isokinetic muscle strength or total work and clinical test results in patients with osteoarthritis (OA) of the knee. METHOD: As part of a prospective, controlled study 43 patients with osteoarthritic changes of both knees (radiographic Kellgren stage II-III) were followed in a right/left comparison. The influence of intraarticularly injected hyaluronic acid (20mg hyaluronic acid/2ml Hyalart) on functional and clinical parameters was analysed. We used the isokinetic system Cybex 600 for measuring maximal isokinetic muscle strength and total work. A total of 20 males and 23 females fulfilled the inclusion criteria with an age between 55-78 years and underwent five injections of hyaluronic acid (one injection per week). The injected knee represented the treatment group, while the contralateral knee served as the control. RESULTS: The maximum peak torque of the knee extensors in the treatment group was measured between 57+/-26.15/32.33+/-19.63Nm prior to the injections and 77.17+/-32.54/47.83+/-21.43Nm following the hyaluronic acid therapy (P< 0.01). The analysis of the knee flexors at angular velocities of 60 degrees /s and 180 degrees /s revealed values of 40.44+/-21.58/22.89+/-16.64Nm and 53.55+/-24.26/34.05+/-17.37Nm (P< 0.01) respectively. The evaluation of the total work of the knee flexors and extensors revealed a significant difference (P< 0.01) between the treatment and control group. The Lequesne score was reduced from 13.57+/-1.88 prior to the injections to 7.94+/-2.53 after the treatment (P< 0.01). The pain score was documented with the help of a visual analog scale. The VAS values were reduced at rest from 3.83+/-1.72cm to 1.36+/-1.42cm and during weight bearing from 7.57+/-1.34cm to 3.75+/-1.32cm in the treatment group (P< 0.01). CONCLUSIONS: This controlled prospective clinical trial confirmed that 5 weekly intraarticular injections of HA (Hyalart) in patients with OA of the knee provide pain relief and functional improvements. (+info)
Reduction of CpG-induced arthritis by suppressive oligodeoxynucleotides.
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OBJECTIVE: Bacterial DNA contains immunostimulatory CpG motifs that cause inflammation when injected into the knee joints of normal mice. We examined whether synthetic oligodeoxynucleotides (ODN) that suppress CpG-induced immune responses prevent CpG-induced arthritis. METHODS: CpG, suppressive, and/or control ODN were injected into the knees of BALB/c mice. Joint swelling and inflammation were evaluated by physical measurement, by histologic analysis of joint tissue, and by magnetic resonance imaging. RESULTS: Immunostimulatory CpG DNA induced local arthritis, characterized by swelling of the knee joints, the presence of inflammatory cell infiltrates, the perivascular accumulation of mononuclear cells, and hyperplasia of the synovial lining. Administering suppressive (but not control) ODN reduced the manifestations and severity of arthritis up to 80%. CONCLUSION: Suppressive ODN may be useful for the prevention or treatment of arthritis induced by bacterial DNA. (+info)
Effect of intra-articular inj-ction of radioactive colloids of erbium and yttrium on the growth of rabbit legs.
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The effect of the intra-articular injection of radioactive erbium 169 and yttrium 90 on the growth of the leg in rabbits has been studied. I colloid state these isotopes are used clinically for synovial ablation. These beta emitters slow down bone growth in proportion to the amount of radioactivity injected. If the joint has previously been damaged by an inflammatory arthritis the effect of the radiation on the bone growth is reduced. (+info)