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Biomedical subjects

B Combe

Publications and source records attributed to B Combe.

At least 91 records · Page 5Linked to original sources
PubMed1992

[Therapeutic maintenance dose with methotrexate in rheumatoid polyarthritis. Prospective study of 191 cases].

One hundred and ninety one patients with rheumatoid arthritis were included in an open prospective trial with the aim of evaluating the acceptability, efficacy and therapeutic maintenance levels of methotrexate. The mean treatment duration was 19 +/- 13.2 (3-58) months and the mean weekly dose of methotrexate 10.2 +/- 0.2 mg. Analysis of the 191 patients by intention to treat showed a statistically significant improvement in all clinical parameters as well as a significant fall in sedimentation rate with a corticosteroid-sparing effect. The therapeutic maintenance level of methotrexate was 73% at one year, 65% at 2 years and 46% at 5 years. Adverse reactions occurred in 71 patients (37.1%) including 30 who stopped methotrexate permanently as a result. With cautious and strict patient selection, methotrexate could be used in RA as basic treatment of first choice.

Adult↗
PubMed1991

The B cell repertoire in rheumatoid arthritis. I. Frequency of EBV-inducible circulating precursors producing autoantibodies.

The frequency of B cell precursors producing antibodies against various autoantigens (Fc fragment of IgG, F(ab')2 fragment of IgG, type II collagen, cytoskeleton filaments and insulin) was determined in patients with rheumatoid arthritis (RA) using immortalization of peripheral blood B cells by the Epstein-Barr virus (EBV) and limiting dilution analysis. Equally large numbers of B cell precursors producing IgM-rheumatoid factors (RFs) were present in the peripheral blood of seronegative and seropositive RA patients and of controls. On average, 1 out of 15,000 B cells could be induced by EBV to secrete IgM-RFs, which represents 0.5-1% of the EBV-induced proliferating clones. By cloning or somatic hetero-hybridization of EBV cell lines derived from patients and controls, we obtained two types of monoclonal RFs: one polyreactive, reacting with Fc but also with the other autoantigens tested, and the other monoreactive, reacting with Fc only and that previously had only been found in the RA B cell repertoire. Moreover, patients and controls had similar numbers of circulating B cell precursors secreting IgM antibodies against other autoantigens that might be regarded as specific targets of RA (F(ab')2 fragment of IgG and type II collagen), and against cytoskeleton filaments that are targets of natural autoantibodies, increased in RA. The frequencies of EBV-induced B cells producing antibodies against all these autoantigens were of the same order of magnitude as the frequency of EBV-induced B cells producing RFs. The patients also possessed a similar number of precursors producing antibodies against insulin, an autoantigen irrelevant to the pathogenesis of the disease, taken as control. These data tend to demonstrate no abnormality in the autoantibody repertoire of B cells activable by EBV in RA, especially those secreting RFs. In vitro spontaneous RF secretion by circulating B cells was observed in seropositive RA patients but not in seronegative patients and in the controls tested. We enumerated the number of B cells spontaneously secreting RFs in seropositive RA patients and found that it correlated with the serum RF titer, but not with the number of RF-secreting B cells activated by EBV. The mean frequency values of B cells secreting RFs either spontaneously or after EBV infection were of the same order of magnitude, showing that the expanded population of in vivo-activated B cells was not (at least partially) infectable by EBV. This raised the possibility that EBV triggers a repertoire which may not reflect the status of B cells secreting autoantibodies in autoimmune diseases.

Age Factors↗
PubMed1991

Treatment of rheumatoid arthritis with methotrexate: a prospective open longterm study of 191 cases.

One hundred and ninety-one patients with severe rheumatoid arthritis (RA) were included in a prospective open longterm study of the safety, efficacy and maintenance of methotrexate (MTX) treatment. The mean duration of MTX treatment was 19 +/- 13.2 (3-58) months; the mean weekly dose of MTX was 10.2 +/- 0.2 mg. Analysis of the 191 patients in an intent-to-treat manner showed a significant improvement of all the clinical variables and a decrease of erythrocyte sedimentation rate with a steroid sparing effect. The probability of continuing MTX therapy for up to 2 years was 65% and for up to 5 years was 46%. Adverse effects of MTX occurred in 37.1% of the patients, but only 15.7% discontinued MTX permanently.

Adult↗
PubMed1990

T cell receptor expression and activation of synovial lymphocyte subsets in patients with rheumatoid arthritis. Phenotyping of multiple synovial sites.

Two-color flow cytometry analysis of peripheral blood and synovial lymphocytes from rheumatoid arthritis patients was performed using monoclonal antibodies directed against T cell subsets, T cell activation markers, and T cell receptors. The results showed an abnormally high percentage (greater than 15%) of CD3+, CD4-, and CD8- T cells expressing a specific receptor containing a gamma chain. Phenotypic analysis of lymphocytes infiltrating both knee joints of individual rheumatoid arthritis patients revealed very similar subset distribution and activation levels, despite strong differences in the clinical status between the 2 sites.

Arthritis, Rheumatoid↗
PubMed1990

Distribution of T-cell receptor-bearing lymphocytes in the synovial membrane from patients with rheumatoid arthritis.

Using immunohistology and monoclonal antibodies directed to the T-cell receptor (TCR) chains, we have analysed the distribution of TCR-bearing lymphocytes within the membrane of rheumatoid arthritis (RA) patients. Alkaline phosphatase staining for TCR alpha beta-bearing lymphocytes showed a distribution paralleling that of the total T cells. Staining for the TCR gamma delta chains revealed a moderate and rather homogeneous distribution of T gamma delta lymphocytes within the RA synovium. As evidenced by simultaneous staining for alpha beta and gamma delta receptors, the relative count of T gamma delta to alpha beta-expressing cells is close to the peripheral count (e.g.5%), and lower than that previously observed in the synovial fluid. Interestingly, the peripheral type V gamma 9-J gamma P rearrangement using the T gamma delta cell subset was relatively decreased in the synovial membrane, as compared to synovial fluid and peripheral blood, suggesting that the T gamma delta distribution in the rheumatoid synovium resembles a thymic-like situation.

Antibodies, Monoclonal↗
PubMed1990

Anti-F(ab')2 antibody response to the injection of anticlass II HLA alloantibodies in patients with rheumatoid arthritis.

Placenta eluted gamma globulins (PEGG) contain antibodies against class II HLA antigens and have been used for treating patients with rheumatoid arthritis (RA). In view of the potential use of antibodies to class II HLA for treating autoimmune diseases we looked for the immunobiological effects of PEGG injections in patients. No modulation of class II HLA was seen at the surface of circulating mononuclear cells after one week of daily PEGG injections. In some patients, antibodies to F(ab')2 fragments of PEGG-IgG were produced. These antibodies reacted against F(ab')2 of any IgG as well and did not prevent anticlass II HLA antibodies from binding to class II HLA, thus showing no characteristics of classical antiidiotypic antibodies. The appearance of anti-F(ab')2 antibodies was not correlated with the clinical course of the disease. Their significance is discussed.

Animals↗
PubMed1990

[Long-term tolerability of tiopronin (Acadione) in the treatment of rheumatoid arthritis. Apropos of 140 personal cases].

One hundred and forty patients with classic or definite rheumatoid polyarthritis were treated with N2 mercapto-propionly-glycine: thiopronine (Acadione) at an average dose of 1 g per day over a mean duration of 11.7 months + 10.7 months. The retrospective study of these cases, followed between 1980 and 1988 by the same medical team, permits to evaluate the long-term tolerance of the product. Adverse reaction, always subsiding were observed in 55 p. cent of the patients, requiring discontinuation of the treatment in 40 p. cent of the cases. These side effects occur in 3/4 of the cases, during the first 6 months of the treatment. The intolerance mainly affect skin and mucosae: 46 cases (32.8 p. cent) resulting in 32 instances (22.8 p. cent) discontinuation of the treatment because of stomatitis, pruritus, various types of erythema, pemphigus (1 case). Fourteen patients presented a renal failure (10 p. cent) requiring in 8 instances (5.7 p. cent) discontinuation of the thiopronine because of nephrotic syndrome (3 case) and proteinuria (5 cases). Haematological disorders were observed in 13 instances (9.2 p. cent), justifying, in 10 instances (7.1 p. cent) discontinuation of the treatment because of thrombopenia or leucothrombopenia. The other side effects observed are the following: digestive disorders 15 cases (10.7 p. cent) requiring discontinuation of the treatment in 3 instances (2.1 p. cent), agueusia in 6 instances (4.2 p. cent) requiring discontinuation of the treatment in one case; miscellaneous disorders 13.5 p. cent for which the responsibility of thiopronine is not precisely established (especially hepatic cholostasis, muscle disorders), requiring discontinuation the the treatment in 1.4 p. cent of the cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗
PubMed1989

[The immunology of rheumatoid arthritis. Influence of basic treatment].

Rheumatoid arthritis is a disease determined and influenced by many factors genetic, environmental, endocrine, psychological and immunological. Immunological mechanisms (hyperexpression of class II HLA antigens, cytokinin anomalies, functional deficiencies of certain lymphocyte categories, polyclonal activation of B lymphocytes with production of antibodies) suffice to maintain between them the immune response, synovial inflammation, and lesions of bone and cartilage. Progress in understanding these diverse pathogenic factors in RA will eventually lead more selectively targeted treatments to supercede the present empirical use of basic treatments.

Arthritis, Rheumatoid↗
PubMed1989

Treatment of chronic knee synovitis with arthroscopic synovectomy after failure of intraarticular injection of radionuclide.

Although satisfactory results have been obtained with conventional synovectomy of the knee, there are frequent complications, and a long period of rehabilitation is necessary after this surgery. We performed arthroscopic synovectomy of the knees of 30 patients (33 knees), 22 of whom had rheumatoid arthritis. These patients underwent the procedure after failure to respond to an intraarticular injection of either osmic acid or yttrium 90. The operated knee was moved 3-5 hours after the arthroscopy, and the patients walked the next day. No rehabilitation was needed. The followup period ranged from 6 months to 36 months, with an average of 17.7 months. Except for 1 patient with severe arthritis, all patients experienced improvement. Results were rated as "good" or "very good" in 27 knees. Six months after synovectomy, the patients were asked to rate their improvement; the mean +/- SEM degree of improvement was 79.1 +/- 22.9%. All patients had significant improvement in the range of motion of the knee. One patient required manipulation of the knee (while under anesthesia) soon after the arthroscopy. There were no other complications. There was no detectable radiographic evidence of disease progression in 24 patients who were seen 1 year after the procedure or in 9 patients who were seen 2 years after the arthroscopy. Thus, arthroscopic synovectomy appears to be an effective and simple treatment for chronic knee synovitis, and has a low morbidity rate.

Adolescent↗
PubMed1989

Clinical significance of anti-RNP and anti-Sm autoantibodies as determined by immunoblotting and immunoprecipitation in sera from patients with connective tissue diseases.

Antibodies to Sm and RNP antigens have been detected by immunoblotting and immunoprecipitation of small nuclear ribonucleoproteins in 168 sera from patients with connective tissue diseases previously characterized by immunodiffusion. Anti-RNP and anti-Sm antibodies immunoprecipitated U1 and U1-U6 snRNA respectively. By immunoblotting anti-Sm reacted with B-B' and D polypeptides and we have distinguished two types of anti-RNP sera: 1) 'full spectrum' anti-RNP sera reacted with the 68 kD, A, C and B-B' polypeptides; 2) 'partially reactive' anti-RNP sera reacted with various combinations of these polypeptides but not the four of them. A strong specificity of anti-Sm antibodies for systemic lupus erythematosus (SLE) was found with all three methods but immunoblotting was more sensitive and detected anti-Sm in 76% of SLE sera. Sera containing a high titer of 'full spectrum' anti-RNP without anti-Sm activity were only detected in mixed connective tissue disease (MCTD) whereas anti-68 kD antibodies alone seemed to be less specific. This strong association between 'full spectrum' anti-RNP antibodies and MCTD supports the hypothesis that MCTD is a distinct clinical entity associated with a specific serologic marker.

Autoantibodies↗
PubMed1988

Rheumatoid nodulosis: report of two new cases and discussion of diagnostic criteria.

Two patients with typical rheumatoid nodulosis are described and compared with 24 reported cases. Rheumatoid nodulosis is a particular variant of rheumatoid arthritis associated with palindromic rheumatism, subcutaneous rheumatoid nodules, mild or no systemic manifestation and a benign clinical course. Positive rheumatoid factor and radiologic subchondral bone cysts are usual, but their absence should not eliminate the diagnosis of rheumatoid nodulosis, particularly at the onset of the disease.

Adult↗