[CTLA4-Ig interferes and downregulates the proinflammatory activities of rheumatoid synovial macrophages in monoculture]. / CTLA4-Ig influenza e inibisce le attività proinfiammatorie di macrofagi sinoviali reumatoidi in monocoltura.

OBJECTIVE: CTLA4-Ig, a biologic agent employed in rheumatoid arthritis (RA) treatment, downregulates the immune response and exerts anti-inflammatory effects acting on different cells including dendritic/T cells interaction and directly on osteoclasts. We investigated the anti-inflammatory effects of CTLA4-Ig in primary monocultures of RA synovial macrophages (SM). METHODS: SM were obtained, from 8 RA patients (7 F, 1 M; DAS28>5.2) who underwent therapeutic arthroscopic synoviectomy and were cultured in the absence and in the presence of CTLA4-Ig at the concentration of [500 microg/ml], the most reliable dose related to the previous pharmacological clinical and experimental experiences. Inflammatory cytokine (IL-6, TNFalpha, IL-1beta) expression was evaluated by immunocytochemistry (ICC with relative image analysis), western blot (WB), and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: ICC analysis revealed that CTLA4-Ig treatment significantly downregulated cytokine expression (p<0.001 for IL-6, TNFalpha and IL-1beta) when compared to untreated RA SM. WB and qRT-PCR confirmed partially the data. CONCLUSIONS: CTLA4-Ig was found to exert a direct and significant anti-inflammatory effect on primary monocultures of RA SM, suggesting a therapeutic power in different phases of the disease activity.

Presence of estrogen-binding sites on macrophage-like synoviocytes and CD8+, CD29+, CD45RO+ T lymphocytes in normal and rheumatoid synovium.

OBJECTIVE: To study the presence of estrogen-binding sites (EBS) in the synovial tissues of male and female patients with rheumatoid arthritis (RA) and in age- and sex-matched healthy controls. METHODS: Both type 1 (high affinity, low binding capacity) and type 2 (reduced affinity, higher binding capacity) EBS were investigated in both soluble and nuclear fractions of homogenized synovial tissue samples by a dextran-coated charcoal method. To determine what type of synovial cell was positive for EBS, cryosections of synovial tissues were immunostained with a specific monoclonal anti-estrogen receptor antibody (anti-ER MAb) using both immunofluorescence and immunoperoxidase techniques. Double immunostaining with the anti-ER MAb and with specific MAb to detect different macrophage antigens (Ber-MAC3, MAC387, CD68) and CD8+ T cell subsets (CD29+, CD45RO+ and CD29-, CD45RO-) was performed. RESULTS: Higher affinity EBS were found mostly in nuclear cell fractions of either RA or control synovial tissues (28 of the 33). These EBS were present to a lesser extent in soluble cell fractions (11 of the 33). Immunostaining showed the estrogen receptor-positive cells to be the macrophage-like synoviocytes and the CD8+, CD29+ T cells both in RA and in control synovial tissues. Higher nuclear content of EBS was consistent with more intense nuclear staining of synoviocytes and T cells. CONCLUSION: It is conceivable that the immunomodulatory activity exerted by estrogens is at least partly mediated through their interaction with EBS that are present on macrophage-like synoviocytes, functioning as antigen-processing and antigen-presenting cells, and on antigen-experienced (memory) CD8+ T lymphocytes (CD29+, CD45RO+).

Evidence for the presence of androgen receptors in the synovial tissue of rheumatoid arthritis patients and healthy controls.

OBJECTIVE: To study the presence of androgen receptors in the synovial tissue of male and female patients with rheumatoid arthritis (RA) and matched healthy controls. METHODS: Both site I (high affinity, low binding capacity) and site II (reduced affinity, higher binding capacity) androgen receptors were investigated in soluble and nuclear fractions of homogenized synovial samples, using the dextran-coated charcoal method. The finding of pure, high-affinity site I receptors in both fractions was considered indicative of androgen receptor positivity. In order to determine what type of synovial cell was positive for androgen receptors, cryosections of synovial tissues were immunostained with a specific monoclonal anti-androgen receptor antibody (MAb), using both immunofluorescence and immunoperoxidase techniques. Double immunostaining with this MAb and specific MAb directed toward different macrophage/granulocyte antigens was also performed. RESULTS: Remarkable differences were found between male and female controls: Most males were positive for androgen receptors, and most females were negative. The fetomolar content of androgen receptor in the nuclear fraction was fairly constant, but the soluble fraction showed a higher femtomolar concentration in female RA patients than in controls of either sex, as well as in male RA patients compared with female RA patients. The androgen receptor-positive cells in both RA and control synovial cryosections were found by immunostaining to be macrophage-like synoviocytes, and were also found to be HLA-DR positive. CONCLUSIONS: The immunosuppressive action exerted by androgens might, at least in part, be mediated through their interaction with macrophage-like synoviocytes functioning as antigen-processing and antigen-presenting cells in rheumatoid synovia.

[Double-contrast arthrography in recurrent luxations of the shoulder]. / L'artrografia a doppio contrasto nella lussazione recidivante della spalla.

One hundred and ninety-three shoulder arthrographies were performed between 1979 and 1985 on patients affected by recurrent dislocations. The diagnostic doubt was cleared up in 162 cases (83%). Arthrographic diagnosis was confirmed by pathological findings in 92% of the patients who underwent surgery. The double-contrast technique under local anaesthesia with anterior access is suggested, since it allows several arthrograms in different projections. Thus, an analytic study of the articular damage can be carried out. The patterns of each projection are briefly shown. Revision of case histories points out that: a) the use of arthrography should always be assessed on a clinical-radiological basis for each patient; b) there is no doubt as to the usefulness of this examination as a direct means of exploration, as far as the articular damage is concerned, not only as an aid to future surgery, but also in the follow-up of the results of the treatment in the long run.

A comparative study of trochanteric and basicervical fractures of the femur treated with the Ender and McLaughlin techniques.

Endomedullary nailing as proposed by Ender is an important alternative in the treatment of trochanteric and basicervical fractures of the femur (Amici et al., 1980; Carret et al., 1980; Ender, 1970; Kempf et al., 1979; Zinghi et al., 1979). Rush's concept (Eiffel Tower, for the distal epiphysis) is reproposed with some variations and transposed to the femoral neck. The aim of the operation differs from that of the nail and plate technique in that, instead of trying to achieve anatomical reconstruction, an immediate functional by-pass of the fractured part is attempted. After using this technique for three years, we compared the old method, which we had not abandoned, the McLaughlin nail and plate, with the new Ender nail.