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Biomedical subjects

A Bussel

Publications and source records attributed to A Bussel.

At least 37 records · Page 2Linked to original sources

A CD2+ subset of non-malignant peripheral blood lymphocytes from patients with Sézary syndromes overexpress the low-molecular-weight GTP-binding protein Rab2.

The Rab branch of the Ras-related GTP/GDP-binding proteins currently includes at least 25 related members which are involved in the intracellular vesicular transport along the secretory and endocytic pathways in eukaryotic cells. The overexpression of the Rab2 protein in peripheral mononuclear cells is demonstrated from 13 out of 17 patients exhibiting a Sézary syndrome. Moreover, this phenomenon is detectable in other lymphoid and myeloid malignancies. Several lines of evidence are shown suggesting that the Rab2 overexpression can be related not to leukemic cells but to a subset of peripheral lymphocytes with a CD2+ phenotype. Our results provides strong evidence for the implication of a small GDP/GTP-binding protein in immunological events associated with neoplastic states. The precise cellular population involved in this process remains to be determined.

Antigens, Differentiation, T-Lymphocyte↗

[Immunoglobulins or plasma exchange? Synchronization of plasma exchange and intravenous polyvalent immunoglobulins. A consecutive study of 11 patients].

Synchronization is defined as a prescription sequence aimed at obtaining synergic response or potentialization. THEORETICAL BASIS--The concept of synchronization is based on clinical and biological observations such as similar indications and transient effectiveness. Certain mechanisms of action such as reduction of pathological autoantibodies and accelerated elimination of immune complexes are common to both methods. Inversely, long-term effects differ. Plasma exchange cannot control the synthesis (or could aggravate) of autoantibodies while gammaglobulins have a suppressor effect on autoreactive clones. The aim is to obtain a summation effect by eliminating immediately cytotoxic factors. The potentializing effect of gammaglobulin anti-idiotypes on the modification of the immunologic repertory is favoured by prior reduction in the level of circulating pathogenic antibodies. RESULTS--It is difficult to evaluate the efficacy of this therapeutic association. Only a few trials have been conducted in refractory autoimmune thrombopenic purpura (n = 8), in intra-uterine Rhesus disease (n = 3), and HIV associated pathologies. We report our experience in 11 patients in a situation of therapeutic failure including three cases of renal transplantation, two cases each of chronic polyradiculoneuritis and neurological paraneoplastic syndromes, and one case each of Wegener's syndrome, polymyositis, sclerokeratitis, and antiphospholipid antibodies during pregnancy. Immunoglobulins were injected at an initial dose of 2 g/kg following at least 3 plasma exchanges. Consolidation cures were then administered every 3 weeks at a dose of 1 g/kg. Two major complications occurred and required interruption of the treatment: acute regressive oligo-anuric renal failure (Wegener) and exacerbation of sclerokeratitis inflammatory lesions. The disease process was controlled in 7 patients. CONCLUSIONS--Despite these promising preliminary results, the proposed combination therapy is not devoid of complications and its cost is high (cost of PE for 500 mg/kg Ig is about 5,000 FF). The next step should be the study of experimental models and prospective trials on pathologies with well characterized immunological features.

Adult↗

Responsiveness of chronic lymphocytic leukemia B cells activated via surface Igs or CD40 to B-cell tropic factors.

Recent studies performed in the laboratory have established that interleukin-4 (IL-4) used in combination with anti-CD40 monoclonal antibody (MoAb) 89 presented on Ltk- mouse fibroblasts stably expressing human Fc gamma RII/CDw32 (referred to as the CD40 system) sustains long-term proliferation of normal human B cells. In the present study, B-cell chronic lymphocytic leukemias (B-CLLs) activated through slgs or CD40 were examined for their capacity to proliferate and differentiate in response to various cytokines. Our results indicate that the outcome of IL-4 stimulation on the in vitro growth of B-CLL depends on the signalling pathway used for their activation. Whereas IL-4 did not display any growth-stimulatory effect on B-CLL activated by Ig cross-linking agents, it could stimulate DNA synthesis and enhance the viable cell recovery when leukemic B cells were cultured in the CD40 system. Most B-CLL samples were induced for IgM synthesis upon Staphylococcus aureus strain Cowan I stimulation. This Ig response was potentiated by IL-2 and antagonized by IL-4. Anti-CD40 MoAb used alone or in combination with cytokines (IL-1 alpha to IL-6, interferon gamma, tumor necrosis factor gamma, and transforming growth factor beta) failed to induce Ig secretion from B-CLL cells. No evidence for Ig isotype switching was obtained with the cytokines listed above, regardless of the mode of activation. Taken together, our results suggest that B-CLL cells can be partially released from their apparent maturation block by IL-2 and Ig cross-linking agents. In contrast, combinations of IL-4 and cross-linked anti-CD40 antibodies induced entry of B-CLL cell into cycle, but poorly stimulated their differentiation into Ig secreting cells.

Adult↗

Lack of superiority of steroids plus plasma exchange to steroids alone in the treatment of polyarteritis nodosa and Churg-Strauss syndrome. A prospective, randomized trial in 78 patients.

OBJECTIVE: To define the most effective treatment for polyarteritis nodosa (PAN) and Churg-Strauss syndrome (CSS). METHODS: We conducted a prospective, randomized, multicenter trial in which 78 patients were randomly assigned to receive either prednisone and plasma exchange (group A; n = 36) or prednisone alone (group B; n = 42) as first-line treatment of PAN and CSS. Patients with hepatitis B virus-related PAN were not included in this study. The end point of the study was control of the disease (recovery and remission) or death. RESULTS: Clinical symptoms and laboratory findings did not differ statistically in the 2 groups at study entry. Initial control of the disease was similar in both groups. The assigned treatment was stopped in 16 patients because of lack of efficacy. Oral cyclophosphamide or dapsone therapy reversed the disease evolution in 7 of these 10 group A patients and in 4 of these 6 group B patients. At 7 years of followup, 56 patients had completely recovered (27 in group A, 29 in group B), 7 patients were in clinical remission, and 15 patients had died (19.2%; 6 group A patients and 9 group B patients). The prednisone-plasma exchange combination was no more beneficial than corticosteroids alone in preventing relapses over the long term. There was no significant difference in the 7-year cumulative survival rates of the two groups (83% and 79%, respectively). CONCLUSION: Based on our data, we conclude that combined treatment with prednisone and plasma exchange is not superior to treatment with prednisone alone and must not be systematically employed for initial treatment of PAN and CSS. In most cases, cyclophosphamide as second-line treatment is effective and well tolerated.

Adult↗

Longterm followup after treatment of polyarteritis nodosa and Churg-Strauss angiitis with comparison of steroids, plasma exchange and cyclophosphamide to steroids and plasma exchange. A prospective randomized trial of 71 patients. The Cooperative Study Group for Polyarteritis Nodosa.

We attempted to define the most effective treatment for polyarteritis nodosa and Churg-Strauss angiitis, with a prospective, randomized, multicenter trial of cyclophosphamide in conjunction with corticosteroids and plasma exchanges, compared to corticosteroids and plasma exchanges. A total of 71 patients who fulfilled clinical, histological and/or arteriographic diagnostic criteria were randomly designated to receive either prednisone and plasma exchanges (group A, n = 39) or cyclophosphamide, prednisone and plasma exchanges (group B, n = 32). The end points of the study were control of the disease (recovery and remission) and death. Upon study entry clinical and laboratory features did not differ in the 2 groups. Treatment was stopped in 19 patients because of ineffectiveness in 10 (9 in Group A) and side effects in 9 (8 in Group B). Initial control of the disease was similar in both groups. At 5 years, 27 patients had completely recovered and 14 patients were in clinical remission. The cyclophosphamide-prednisone-plasma exchange association was beneficial in preventing relapses during longterm followup. Nineteen deaths were reported during the followup period. There was no difference between the 10 year cumulative survival rates of the 2 groups (respectively, 72 and 75%). Thus, the association of cyclophosphamide with corticosteroids and plasma exchanges reduced the incidence of relapses and improved the quality of the clinical response to therapy.

Adolescent↗

Peripheral polyneuropathies associated with monoclonal IgM. Antibody activity of monoclonal IgM and therapeutic implications.

Monoclonal IgM from patients with peripheral neuropathy react in nearly 80% of the cases with some components of myelin. The main target is myelin associated glycoprotein (50% of the cases); several types of glycolipids or gangliosides have been identified as the reactive antigen in the other cases. Anti-MAG IgM share little cross reactive idiotopes. Only primate antisera identified a combining site related public idiotope. In fact, these IgM use various light and heavy chains belonging to different variability subgroups. The preliminary results of an ungoing trial aimed to establish the benefit of plasmapheresis in these patients are discussed.

Adult↗

[Comparative study of the efficacy and tolerability of 2 plasma substitutes used as vascular-loading solutions during plasma exchange].

A 4% human albumin solution in association with colloids was tested in an attempt to reduce the cost of replacement fluids during plasma exchange. In a retrospective study, from May 1988 to December 1989, the efficiency and tolerance of gelatin (Plasmion) and dextran 40 (Plasmacair) were compared. Since June 12, 1989, dextran 40 infused only after administration of dextran 1000 (Promit). Seven hundred and forty eight plasma exchanges were performed in 75 patients; 37 received gelatin (7.24 plasma exchanges/patient), 50 dextran (9.6 plasma exchanges/patient) and 12 both solutions after clinical evidence of intolerance to gelatin. No reaction was noted with dextran 40 used alone or in association with haptenic prevention. The gelatin solution induced 2 immediate allergic reactions and one delayed cutaneous reaction. No cross-reactive allergy was observed between the 2 colloids. Dextran 1000 injections were well tolerated. Gelatin infusions were associated with 10 times more episodes of hypovolemia (5.6 versus 0.62%). This difference is probably linked to a faster elimination of gelatin from the vascular compartment and necessitates the infusion of a larger volume of gelatin, as compared to dextran 40, for the same volume of plasma exchanged.

Drug Hypersensitivity↗

Treatment of severe cytomegalovirus infection with ganciclovir and high-dose intravenous immunoglobulin in patients with allogeneic bone marrow transplants. A pilot study.

Cytomegalovirus (CMV) infection is the leading infectious cause of death after bone marrow transplantation (BMT) because of the high mortality rate associated with CMV pneumonia. However, very interresting results were recently reported when treating CMV penumonia with the combination of ganciclovir and high doses of intravenous anti-CMV immunoglobulin. In order to achieve an even better therapeutic efficacy, we have conducted a pilot study consisting of early administration of the combination therapy, as soon as CMV was isolated from the material obtained by bronchoalveolar lavage (BAL). A BAL was performed when symptoms of severe CMV infection were present and sometimes also systematically when an asymptomatic CMV viremia was diagnosed. Out of 18 BMT patients with CMV isolated from BAL in the absence of pulmonary signs, 9 became long-term survivors without any episode of CMV pneumonia and 9 died. However, only 2 patients died because of CMV pneumonia. Early treatment with the combination of ganciclovir and anti CMV immunoglobulin seems thus to decrease the incidence of CMV pneumonia (2/18) as it is known that about half of the untreated patients with CMV viremia will develop CMV pneumonia. We have also used the combination therapy to treat 3 cases of CMV pneumonia. As 2 patients survived the CMV pneumonia episode, this confirms the possible effectiveness of the combination therapy for the treatment of established CMV pneumonia. However, our pilot study points out the usefulness of an early treatment. At such an early stage, application of the combination therapy could affect the intensity and length of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Transplantation↗

Treatment of progressive systemic sclerosis by plasma exchange: long-term results in 40 patients.

The efficacy of plasma exchanges (PE) during the course of scleroderma has only been investigated for short periods. The aim of this study was to follow patients over a long enough period to observe the course of the clinical and paraclinical symptoms in the short, medium, and long term. Forty patients, 24 women and 16 men, were treated by PE and observed for 1-3, 3-12 and over 12 months. Immunological, biological and clinical course and any undesirable side effects were evaluated using a detailed questionnaire. Concomitant therapies were reported and most frequently consisted of corticosteroids, colchicine, factor XIII or vasodilators (nifedipine, captopril). The therapeutic effectiveness of PE was assessed on the basis of improvements in cutaneous, digestive, joint, muscular, lung, cardiovascular and renal lesions. Our findings confirmed the effectiveness of short-term PE on scleroderma (52% of the patients improved during the first 3 months). However, this improvement was transient (5% improvement between 3 and 12 months and only 2.5% over 12 months) and limited to the cutaneous and muscular lesions. Thus, PE cannot be recommended for the treatment of progressive systemic sclerosis.

Adolescent↗