[Value of orthesis canes in rheumatoid polyarthritis].
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Biomedical subjects
Publications and source records attributed to B Combe.
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A double-blind multicenter study comparing the effect of placenta eluted IgG and venoglobulins in the treatment of rheumatoid arthritis was conducted in 113 hospitalized patients. Rheumatoid arthritis was severe, classical (92 cases) or definite (21 cases), seropositive in 87 cases, with nodules in 32 cases; the mean duration of the disease was 10 years. The majority of patients had previously received numerous slow-acting drugs without result or with side-effects. A statistically significant decrease of all the quantitative indices but one (grip strength) was obtained with both products on the 8th day of treatment; the effect of placenta eluted IgG was statistically superior for the number of swollen joints (P less than 0.025), Ritchie's index (P less than 0.0005) and some extra-articular manifestations. There was no significant decrease in associated treatments and biological parameters (erythrocyte sedimentation rate, rheumatoid factor). Tolerance was excellent; some cases of benign venulitis were observed; treatment was never discontinued on account of side-effects. Further placebo-controlled of each of these immunoglobulins of placental origin are needed for firm conclusions to be drawn.
The regulation of interleukin-2 (IL-2) production was investigated using mononuclear cells from synovial fluid (SF) and peripheral blood of 12 patients with classical and active rheumatoid arthritis. Decreased phytohemagglutinin (PHA) stimulated IL-2 production by lymphocytes was observed in rheumatoid peripheral blood (5.3 +/- 10.9 units/ml) and SF (3.8 +/- 5.2 units/ml) compared to peripheral blood from 12 normal donors (18.1 +/- 15.4 units/ml) and SF from 5 patients with other rheumatic diseases (11.9 +/- 10.9 units/ml). Indomethacin, phorbol myristate acetate and irradiation of suppressor cells increased IL-2 values in rheumatoid SF and peripheral blood but did not restore normal IL-2 production. IL-2 production did not correlate with clinical activity in patients with RA.
Twelve patients suffering from an inflammatory rheumatic disorder with chronic synovitis of the knee joint were treated by synovectomy using a pneumatic chondrotome under arthroscopic control in combination with abundant articular lavage. All patients had been treated with one or several chemical or radioisotopic synovial instillations followed by failure of treatment or a rapid recurrence of synovitis. Eight patients had a rapid and good or very good therapeutic result with regression of synovitis and of pain during the first month after the synovectomy. This result appears to be maintained more than one year later in the case of the first patients treated. Four patients had a manifest but incomplete improvement. Postoperative follow-up was unremarkable, hospitalization period was short, and no physical rehabilitation was necessary. However, one patient developed stiffness of the knee joint which required its movement under general anesthesia. Arthroscopy with synovectomy and articular lavage appear to offer an interesting therapeutic resolution in case of chronic synovitis unresponsive to medical measures, both locally and systemically administered. Short-term results appear better than those obtained with conventional surgical synovectomy and postoperative follow-up is much simpler.
The authors have studied the case of a female patient with rheumatoid polyarthritis, who developed a lymphocytic proliferation in the blood, the marrow, and the liver, associated with a neutropenia. Several similar cases have been recently reported in the literature. The cellular proliferation is made of large granulous lymphocytes and the study of membrane markers enables to find the following homogeneous phenotype: E rosette+, CD8+, HNK-1+, FcR+, CD4-luminal diameter "divided by degrees - -, IgS-, HLA class II-. This lymphocytic sub-population produces little interleukin-2, responds weakly to mitogens (PHA, CON A, PWM), and inhibits the response of normal lymphocytes to the same mitogens. These lymphocytes have a weak natural killer activity but, on the contrary, develop a very strong cytotoxic activity which is antibody-dependent. Clinically, splenomegaly, anemia and infections are frequent and hepatomegaly or thrombopenia more rare. Adenopathies are never present. The evolution is chronic in nature and not very aggressive, although the lymphocytic proliferation is monoclonal in origin, as demonstrated in molecular biology studies. The neutropenia might be secondary to an inhibiting effect of lymphocytes on the granular precursors of the bone marrow. There is a definite association between this lympho-proliferative syndrome and rheumatoid polyarthritis, and this association appears to be different from the Felty's syndrome.
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We describe a rheumatoid arthritis patient who was found to have chronic T cell lymphocytosis and neutropenia. She had an increased number of lymphocytes in the peripheral blood, bone marrow, and liver, and the expanded lymphocyte subset consisted of large granular lymphocytes with a homogeneous phenotype. Of the previously described patients with these large granular lymphocytes, almost one-fourth have had rheumatoid arthritis.
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Thirty-one patients with severe rheumatoid arthritis were treated with intravenous perfusion of human placenta-eluted gammaglobulins. These gammaglobulins, which are IgG eluted from placental tissue, have strong immunomodulating properties in vitro. Several clinical trials were tested to find the optimal useful dosage. A 50 percent improvement was considered a good result and was obtained in 60 percent of patients with rheumatoid arthritis. The best results were obtained in patients receiving 1,500 mg daily seven days each month. Six subjects had a long remission of their disease after the end of treatment. The side effects were usually minor. In all patients, an immunostimulation of lymphocyte function was shown, even when they had no improvement. A control group of patients underwent perfusion with IgG from placental blood without any clinical or immunologic effect. It is suggested that the in vivo effects of placenta-eluted gammaglobulins might be mediated by polyspecific anti-HLA-DR antibodies.
The activity of natural killer cells in the synovial fluid, the synovial tissue and the peripheral blood was studied in 23 patients with active rheumatoid arthritis and was found to be significantly lower than that in the blood of 28 controls. This decrease was inversely related to the erythrocyte sedimentation rate. The preincubation of mononuclear cells with indomethacin significantly increased the natural killer activity in the blood of the controls and the patients with rheumatoid arthritis, but did not have any effect in the synovial compartment. The elimination of the adherent cells increased the natural killer activity in the blood of the controls and the patients with rheumatoid arthritis, but decreased this activity in the synovium. The stimulatory effect of synovial macrophages and the suppressor effect of the blood macrophages on the natural killer activity were confirmed when the adherent and non-adherent populations were mixed and these effects were reproduced by using supernatants of total mononuclear cells. The stimulation of the natural killer activity by interleukin 2 and poly-I:C, an interferon inducer, is independent of the macrophages in rheumatoid arthritis. These results suggest a deficient natural killer activity in active rheumatoid arthritis and a difference in the modulation of these natural killer cells by macrophages in rheumatoid synovium and normal or rheumatoid arthritis blood.
Several aspects of interleukin-2 (IL-2) generation and function were studied employing mononuclear cells from synovial fluid (SF), synovial tissue (ST) and peripheral blood (PB) of patients with rheumatoid arthritis (RA). Decreased PHA stimulated IL-2 production by lymphocytes from rheumatoid ST, SF (P less than 0.02), and PB (P less than 0.01) was observed when compared to normal blood and SF of patients with gout. The proliferative response of rheumatoid lymphocyte blasts exposed to exogenous IL-2 was also defective (P less than 0.05-0.001). This defect was greater in SF than in rheumatoid PB (P less than 0.05-0.001). In addition to the proliferative response, the effect of IL-2 on interferon-gamma (IFN-gamma) production was also examined. Rheumatoid lymphocytes from both PB and SF produced less IFN-gamma after overnight treatment with IL-2 than did normal PB lymphocytes. This decreased IFN-gamma induction was discordant with the excellent enhancement by IL-2 of natural killer activity. Removal of adherent cells in synovial fluid did not correct this deficit. Abnormalities in the biology of IL-2 and IFN-gamma suggest that impaired T cell function could contribute to the immunopathogenesis of RA.
Natural killer (NK) cell activity and its regulation in synovial fluid (SF), synovial tissue (ST), and peripheral blood (PB) was studied in 23 patients with active rheumatoid arthritis (RA). NK activity was reduced in PB (P less than 0.005), SF (P less than 0.002), and ST of patients with RA compared to the PB of 28 healthy controls. NK activity in SF was inversely correlated with disease activity as measured by erythrocyte sedimentation rate (r = -0.561; P less than 0.02). Poly I:C, an interferon inducer, stimulated NK activity in RA patients' PB and SF and control subjects' PB to similar extents. However, augmentation of NK activity by interleukin-2 was significantly greater in SF than in PB of RA (P less than 0.02). Preincubation of mononuclear cells with indomethacin significantly increased the NK activity of normal and RA PB but had no effect on that of SF. These observations suggest that the NK activity may be reduced in both PB and SF of RA and that functional differences between populations of cells with NK-like activity and/or differences in the control or modulation of NK activity exist between PB and SF.
Recently, in another study, we observed that indomethacin, a prostaglandin synthetase inhibitor, significantly increased NK activity in both normal and rheumatoid arthritis (RA) peripheral blood (PB) but not in RA synovial fluid (SF). Because macrophages are a major source of prostaglandins, we examined the effect of macrophage-enriched adherent cells (AC) on NK activity as measured by a 3-hr Cr-release assay with K 562 cells. The removal of AC resulted in increased (p less than 0.01) NK activity in both normal and RA PB. In contrast, the removal of AC from RA SF resulted in a significant decrease (p less than 0.001) of NK activity. By using only nonadherent cells (NAC), NK activity in RA SF and synovial tissue (ST) was significantly reduced when compared to autologous RA PB (p less than 0.001). Enhancement of NK activity of SF NAC by both poly I:C and IL 2 was not dependent on AC. Mixing experiments demonstrated that the addition of synovial AC for 16 hr increased NK activity of synovial NAC to a level similar to that of unseparated mononuclear cells, whereas autologous PB AC suppressed NK activity of PB NAC. PB AC, when added to SF NAC, also increased NK activity. Supernatants from synovial mononuclear cells were stimulatory of synovial NAC NK activity, whereas normal PB mononuclear supernatants were suppressive. These observations document 1) a significant reduction of NAC-mediated NK activity in the rheumatoid joint as compared to PB from the same patient, and 2) that AC modulate NK activity differently in the rheumatoid joint as compared to RA or normal PB.
Arthroscopy of the knee, including synovial biopsy under direct vision, was performed in 22 patients (21 cases of arthritis, 1 of osteoarthrosis), treated 15 days to 12 months previously by osmic or isotopic synoviorthesis. The aspects seen after the 16 failures were compared with those seen after good results (4 cases) and after recurrences (2 cases). In arthritis, failure was due either to persistent synovitis, to synovial necrosis or to a combination of the two. Arthroscopy is useful since the discovery of inflammatory lessions justifies repeat synoviorthesis, whilst necrosis indicates the need for articular lavage.
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Spondylodiscitis due to Citrobacter diversus is rare. An unusual case of bifocal cervical spondylodiscitis following transurethral prostatectomy is reported. C. diversus was detected by urinary cultures and locally by intervertebral disc puncture. Satisfactory recovery occurred after treatment with imipenem and amikacin, and then imipenem alone. Citrobacter infections are still rare in adults but are increasing in immunocompromised patients and sometimes occur in healthy subjects following surgery.
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