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Biomedical subjects

L Macchioni

Publications and source records attributed to L Macchioni.

8 recordsLinked to original sources

Evidence that cytosolic phospholipase A2 is down-regulated by protein kinase C in intact human platelets stimulated with fluoroaluminate.

We reported that protein kinase C (PKC) inhibitors increase the release of arachidonic acid induced by fluoroaluminate (AlF4-), an unspecific G-protein activator, in intact human platelets. Now we demonstrate that this effect is independent of the extracellular Ca2+ concentration and that AlF4(-)-induced release of AA is abolished by BAPTA, an intracellular Ca2+ chelator, even in the presence of GF 109203X, a specific and potent PKC inhibitor. This compound also blocks the liberation of the secretory phospholipase A2 in the extracellular medium, indicating that this enzyme is not involved in the potentiation of arachidonic acid by PKC inhibitors. On the other hand, the latter effect is completely abolished by treatment of platelets with AACOCF3, a specific inhibitor of cytosolic phospholipase A2 (cPLA2). These observations indicate that cPLA2 is responsible for the AlF4(-)-induced release of arachidonic acid by a mechanism that is down-regulated by PKC.

Aluminum

Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome: a prospective follow up and magnetic resonance imaging study.

OBJECTIVE: To determine the clinical characteristics of patients with "pure" remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome, and to investigate its relation with polymyalgia rheumatica (PMR). Magnetic resonance imaging (MRI) was used to describe the anatomical structures affected by inflammation in pure RS3PE syndrome. METHODS: A prospective follow up study of 23 consecutive patients with pure RS3PE syndrome and 177 consecutive patients with PMR diagnosed over a five year period in two Italian secondary referral centres of rheumatology. Hands or feet MRI, or both, was performed at diagnosis in 7 of 23 patients. RESULTS: At inspection evidence of hand and/or foot tenosynovitis was present in all the 23 patients with pure RS3PE syndrome. Twenty one (12%) patients with PMR associated distal extremity swelling with pitting oedema. No significant differences in the sex, age at onset of disease, acute phase reactant values at diagnosis, frequency of peripheral synovitis and carpal tunnel syndrome and frequency of HLA-B7 antigen were present between patients with pure RS3PE and PMR. In both conditions no patient under 50 was observed, the disease frequency increased significantly with age and the highest frequency was present in the age group 70-79 years. Clinical symptoms for both conditions responded promptly to corticosteroids and no patient developed rheumatoid arthritis during the follow up. However, the patients with pure RS3PE syndrome were characterised by shorter duration of treatment, lower cumulative corticosteroid dose and lower frequency of systemic signs/symptoms and relapse/recurrence. Hands and feet MRI showed evidence of tenosynovitis in five patients and joint synovitis in three patients. CONCLUSION: The similarities of demographic, clinical, and MRI findings between RS3PE syndrome and PMR and the concurrence of the two syndromes suggest that these conditions may be part of the same disease and that the diagnostic labels of PMR and RS3PE syndrome may not indicate a real difference. The presence of distal oedema seems to indicate a better prognosis.

Age Distribution

Distal extremity swelling with pitting edema in psoriatic arthritis: evidence of 2 pathological mechanisms.

Distal extremity swelling with pitting edema due to altered lymphatic drainage has been reported in some patients with psoriatic arthritis (PsA). The edema usually affected the upper limbs in an asymmetric pattern and was resistant to therapy. We describe 2 additional cases. The distal swelling and pitting edema responded promptly and completely to corticosteroids in the first patient but persisted in the second. Lymphoscintigraphy and magnetic resonance imaging (MRI) revealed a predominant tenosynovitis in the hand without lymphedema in the first patient, and impaired lymphatic drainage without tenosynovial sheath involvement in the second. We conclude that 2 different mechanisms, characterized by a different response to therapy, may be associated with the same clinical picture of distal swelling with pitting edema in patients with psoriatic arthritis. Lymphoscintigraphy and MRI are useful in defining the structures involved and in predicting the prognosis.

Adult

Psoriatic arthritis.

Recent population-based studies have examined the incidence, prevalence, and survival rates of patients with psoriatic arthritis (PsA). Although there are still no completely satisfactory diagnostic criteria for PsA, Moll and Wright's criteria--although not a true classification/diagnostic scheme--are the most used. The sensitivity of these criteria is low (61%), as are the sensitivities of the European Spondyloarthropathy Study Group and Amor classification criteria for the whole spectrum of spondyloarthropathy. In some patients, PsA can occur only with peripheral enthesitis, particularly Achilles tendinitis or dactylitis. These patients may represent a subset of PsA that is not defined by the Moll and Wright or European. Spondyloarthropathy Study Group criteria and is, therefore, poorly recognized as such. Recent studies have analyzed the expression of adhesion molecules, cytokines, and chemokines in the synovial fluid and synovial membrane of patients with PsA. The therapeutic approach to PsA must be multidisciplinary, involving dermatologists and rheumatologists. Currently the most widely used second-line drugs are methotrexate, sulfasalazine, and cyclosporine. Used in combination, these drugs will probably become a well-established therapy for PsA.

Arthritis, Psoriatic

Proximal bursitis in active polymyalgia rheumatica.

BACKGROUND: The cause of musculoskeletal symptoms in the proximal extremities of patients who have polymyalgia rheumatica is not completely understood. The diffuse and severe discomfort can only be partially explained by the mild joint synovitis that is observed in these patients. OBJECTIVE: To determine the involvement of the synovial structures of the shoulder girdle of patients who have active symptoms of polymyalgia rheumatica. DESIGN: Case-control study. SETTING: 2 secondary referral centers of rheumatology. PATIENTS: 13 case-patients who had active symptoms of polymyalgia rheumatica seen during a 6-month period, 9 control-patients who had early symptoms of elderly-onset rheumatoid arthritis, and 10 age-matched healthy controls. MEASUREMENTS: Magnetic resonance imaging of the shoulder was done on the 13 case-patients, 9 control-patients, and 10 healthy controls. RESULTS: The frequency of subacromial and subdeltoid bursitis was significantly higher in the case-patients (who had polymyalgia rheumatica) than in the control-patients (who had elderly-onset rheumatoid arthritis). The frequencies of synovitis of the joints and tenosynovitis of the biceps did not significantly differ between the 13 case-patients and the 9 control-patients. None of the healthy controls showed evidence of fluid accumulation in the joints, bursae, or sheaths of the long head of the biceps. CONCLUSIONS: Inflammation of subacromial and subdeltoid bursae in association with synovitis of the glenohumeral joints and tenosynovitis of the biceps may contribute to the diffuse discomfort in the shoulder girdle observed in patients with polymyalgia rheumatica.

Aged

Therapy with cyclosporine in psoriatic arthritis.

OBJECTIVE: To evaluate the efficacy and toxicity of cyclosporin A (CsA) in the treatment of patients with psoriatic arthritis (PsA). METHODS: We reviewed the literature dealing with CsA treatment of PsA. RESULTS: In the 1980s, some studies evaluating CsA in severe cases of psoriasis documented an improvement in the associated arthritis. Subsequently, open prospective studies included patients with active peripheral arthritis. Using initial CsA dose of 3 to 6 mg/kg/day, improvement in the clinical parameters was noted. A controlled trial showed that CsA and methotrexate (MTX) are equally effective treatment for PsA. CsA and MTX combination was effective in PsA patients resistant to previous second-line therapy. No studies have evaluated the efficacy of CsA on axial disease and on the progression of radiological damage. The most important side effect was nephrotoxicity. However, of 170 CsA-treated patients in 16 studies, only 10 (6%) discontinued the drug because of renal side effects. CONCLUSIONS: CsA seems to be an effective and safe therapy for PsA. However, controlled studies on large number of patients are necessary.

Antirheumatic Agents