Search PubMed⌕ Search

Biomedical subjects

M G Malaise

Publications and source records attributed to M G Malaise.

At least 19 recordsLinked to original sources

[Gout].

In the presence of a clinical acute monoarthritis, a differential diagnosis has to be made between septic arthritis, gout and diffuse chondrocalcinosis. Gout comes from a purine nucleotide metabolism disorder leading to serum urate level elevation. This hyperuricemia can lead to the deposition of monosodium urate crystals in the joints, causing acute attacks. After long-term evolution, others tissues as the kidneys can be involved: it is chronic gout. The definite diagnosis is based on the presence of monosodium urate crystals in the joint fluid. The diagnosis of gout should prompt a search for associated medical conditions that may affect both urate levels and longevity. These include alcoholism, various nephropathies, myeloproliferative disorders, and hypertension.

Arthritis, Infectious↗

[Familial Mediterranean fever].

Familial Mediterranean Fever (FMF) is an hereditary disease that especially affects people living around the Mediterranean sea. It is characterized by recurring fever and abdominal pain, eventually associated with localised pleuritis, synovitis or skin inflammation. The most serious complication is amyloidosis, which can lead to terminal renal failure. The attacks and complications can be avoided by life long administration of colchicine. Two independent French and American teams discovered the gene responsible for the disease in 1997. It encodes for a protein named pyrin/marenostrin involved in the homeostasis the inflammatory mechanisms. The main mutations have been identified and are henceforth accessible for molecular screening.

Amyloidosis↗

[Etoricoxib (Arcoxia)].

Etoricoxib (Arcoxia) is a novel non steroidal anti-inflammatory drug (NSAID) that selectively inhibits the inducible form of cyclo-oxygenase (COX), COX-2. Etoricoxib has a higher COX-1/COX-2 selectivity ratio than the other COX-2-selective NSAIDs as rofecoxib, valdecoxib or celecoxib. Tablets of 60, 90 and 120 mg are available. The recommended dosage of etoricoxib is 60 mg/day for osteoarthritis, 90 mg/day for rheumatoid arthritis and 120 mg/day for acute gouty arthritis. Etoricoxib's efficacy has been widely studied in comparative studies, showing the same efficacy as non-COX-2 selective NSAID, with fewer gastro-intestinal adverse effects.

Administration, Oral↗

Efficacy and safety of the fully human anti-tumour necrosis factor alpha monoclonal antibody adalimumab (D2E7) in DMARD refractory patients with rheumatoid arthritis: a 12 week, phase II study.

OBJECTIVES: To evaluate efficacy, dose response, safety, and tolerability of adalimumab (D2E7) in disease modifying antirheumatic drug (DMARD) refractory patients with longstanding, active rheumatoid arthritis (RA). METHODS: During a 12 week, double blind, placebo controlled study, 284 patients were randomly allocated to receive weekly subcutaneous injections of adalimumab 20 mg (n = 72), 40 mg (n = 70), or 80 mg (n = 72) or placebo (n = 70) without concomitant DMARDs. RESULTS: Adalimumab significantly improved the signs and symptoms of RA for all efficacy measures. ACR20 responses with adalimumab were significant at each assessment versus placebo (p</=0.01). Additionally, ACR responses with adalimumab were achieved more rapidly than with placebo, with 82/115 (71%) of the ultimate ACR20 response rate to adalimumab treatment achieved at week 2. At week 12, for adalimumab 20, 40, and 80 mg, ACR20 response rates were 50.7%, 57.1%, and 54.2%, respectively, versus 10.0% for placebo (p</=0.001 for all comparisons); ACR50 rates were 23.9%, 27.1%, and 19.4%, respectively, versus 1.4% for placebo (p</=0.001 for all comparisons); and ACR70 rates were 11.3%, 10.0%, and 8.3%, respectively, versus 0.0% for placebo (p</=0.05 for all comparisons). All adalimumab doses significantly improved all ACR core criteria at all assessments. The 40 mg and 80 mg doses provided similar benefit. Adalimumab at all doses was generally well tolerated, with only mild or moderate adverse events. Completion rates were 87% for adalimumab and 67% for placebo. CONCLUSIONS: Adalimumab given as monotreatment to patients with longstanding, severe RA refractory to traditional DMARDs produced a rapid, sustained response and was safe and well tolerated, with no dose limiting side effects.

Adalimumab↗

Increased matrix metalloproteinase-3 serum levels in rheumatic diseases: relationship with synovitis and steroid treatment.

OBJECTIVE: To determine matrix metalloproteinase-3 (MMP-3) serum levels in patients with rheumatic diseases and to study the relation between MMP-3 and C reactive protein (CRP) levels. METHODS: MMP-3 serum levels were determined by enzyme linked immunosorbent assay (ELISA) in (a) patients with active inflammatory rheumatic diseases: rheumatoid arthritis (RA), psoriatic arthritis, polymyalgia rheumatica, acute crystal arthritis, and ankylosing spondylitis; (b) patients with active inflammatory systemic diseases: cutaneo-articular or renal systemic lupus erythematosus (SLE), systemic sclerosis, and vasculitides; (c) patients with non-inflammatory rheumatic diseases: osteoarthritis and fibromyalgia; (d) critically ill patients without rheumatic diseases, representing an acute inflammatory control group; (e) healthy controls. RESULTS: MMP-3 serum levels were significantly increased in patients with active RA, psoriatic arthritis, and polymyalgia rheumatica, whether treated or not by corticosteroids, and in female patients with acute crystal arthritis. MMP-3 serum levels were normal in steroid-free patients with active cutaneo-articular or renal SLE, systemic sclerosis, and vasculitides but were significantly increased in steroid treated patients. MMP-3 levels were normal in fibromyalgia, osteoarthritis, ankylosing spondylitis, and acute inflammatory controls. MMP-3 was significantly correlated with CRP in RA (r=0.5, p=0.0004) but not in any of the other disease groups. CONCLUSIONS: MMP-3 serum levels are increased in inflammatory rheumatic diseases characterised by joint synovitis, such as RA, polymyalgia rheumatica, psoriatic arthritis, and acute crystal arthritis-that is, whether the diseases are acute or chronic, erosive or not. They are normal in SLE, systemic sclerosis, and vasculitides as well as in non-rheumatic inflammatory controls, but are significantly increased by steroids. These data strongly suggest that serum MMP-3 reflects synovial inflammation.

Adult↗

[Chronic thoracic pain].

The etiological diagnosis of chronic thoracic pain is wide, from benign mechanical disorders to tumors. Reaching the exact diagnosis in often time consuming. Despite the availability of new techniques of imagery, a meticulous clinical history and physical examination remain mandatory. They will lead the exploration. Idiopathic intercostal neuralgia does not exist.

Aged↗

[Osteoporosis and demineralization: a semantic confusion].

Osteoporosis is the most frequent demineralizing disease. However, when a demineralized vertebra is identified, other diseases must be ruled out in the course of diagnosis. Through three clinical cases, we analyze pitfalls that have delayed the diagnosis of one rare, but unfortunately lethal, aetiology: multiple myeloma.

Aged↗

[Synovial metastases from colonic cancer presenting as arthritis of the knee. Characterization by 18FDG PET scan].

A case of carcinomatous monoarthritis involving the left knee due to colonic adenocarcinoma is described. Large recurrent synovial effusion, that will be later hematic, lytic lesion of the bones and chondrolysis were noted. Knee positron emitting tomography scan using FDG (FDG-PET) revealed a diffuse increased uptake in soft tissues assumed to be synovium, the hypertrophy of which was identified by ultrasonography. Whole body PET scan showed extensive lymph node, visceral and bone metastases, suggesting that the increase in the synovium could also be of metastatic origin. The final diagnosis of synovial carcinomatosis secondary to the known colonic adenocarcinoma was confirmed by histological analysis of biopsies obtained by arthroscopy. A review of the literature is realised. To our knowledge, this is the first synovial metastasis studied by FDG-PET.

Adenocarcinoma↗

[How I treat...rheumatoid arthritis. The arrival of a new therapeutic era: anti-tumor necrosis factor alpha antibodies].

Rheumatoïd arthritis (RA) is the most frequent autoimmune inflammatory arthropathy. Chronic synovial inflammation usually results in cartilage destruction, bone erosion and subsequent joint deformities with impaired physical function. These consequences are more or less delayed by standard disease-modifying antirheumatic drugs (DMARDs). A better knowledge of the basic mechanisms of the disease and new biomolecular tools led to the development of novel biological agents including TNF alpha blockers. TNF alpha is a key inflammatory cytokine that plays a critically important role in the pathogenesis of RA. TNF alpha blockers brought dramatic improvements in efficacy of RA treatment. Here we will review the pathophysiological elements of RA wich explain the therapeutic efficacy of these TNF alpha blockers and we will describe in details the molecules, Remicade (Infliximab) and Enbrel (Etanercept), wich will be very soon used in daily practice in Belgium.

Antibodies, Monoclonal↗

Increased synovial fluid levels of soluble CD23 are associated with an erosive status in rheumatoid arthritis (RA).

Synovial fluid (SF) levels of soluble CD23 (sCD23) were determined in 96 patients presenting with an inflammatory knee effusion (73 with RA and 23 with reactive arthritis (ReA) serving as a control inflammatory non-erosive group) and were correlated with the degree of joint destruction, with local immune parameters (IL-1beta, IL-3, IL-4, IL-6, IL-8, IL-10, IL-12 and sCD25) and with serum markers of inflammation, C-reactive protein and erythrocyte sedimentation rate. RA patients, classified as erosive or not according to Larsen's grade, were separated as follows: (i) 13 patients with non-erosive RA; (ii) 16 RA patients with erosions in hands but not in knees, matched for disease duration with the first group; (iii) 44 RA patients with hand and knee erosions, matched with the second group for rheumatoid factor positivity but of longer disease duration. SF sCD23 levels were significantly increased in both erosive RA groups compared with non-erosive diseases, whether RA or ReA (P < 0.05), whose SF levels were not different. SF IL-10 showed a similar profile to that of SF sCD23 and was the only other parameter characteristic of erosive RA, but no direct correlation was found between the two. SF sCD23 was significantly correlated with IL-12 (r = 0.65, P = 0.0001) and sCD25 (r = 0.39, P = 0.0019) exclusively in the two erosive RA populations. In conclusion, these data showing that increased levels of sCD23 are not only found in the SF of erosive joints but also in knee SF of patients with erosive RA but without knee x-ray-diagnosed erosions suggest that this parameter might be of predictive value for joint destruction. Longitudinal studies are however needed to confirm its potential clinical interest.

Adult↗

Synovial fluid matrix metalloproteinase-3 levels are increased in inflammatory arthritides whether erosive or not.

OBJECTIVE: To study the levels of matrix metalloproteinase-3 (MMP-3) in the knee synovial fluid (SF) of inflammatory arthropathies (rheumatoid arthritis whether erosive or not, reactive arthritis, acute crystal arthritis) and degenerative arthropathies [chronic crystal disease, osteoarthritis and (control) meniscus pathology] and to correlate them with the degree of joint destruction, local inflammatory and immune parameters and systemic markers of inflammation. METHODS: SF levels of MMP-3 (precursor, active and tissue inhibitor of MMP-bound forms), tumour necrosis factor (TNF) alpha, soluble TNF receptors I and II, interleukin (IL)-6 and soluble IL-6 receptor were measured by ELISA in 107 inflammatory and 53 degenerative arthropathies. RESULTS: MMP-3 levels in SF were (i) significantly higher in inflammatory than in degenerative arthropathies; (ii) not related to the degree of joint destruction; (iii) significantly correlated with the levels of all SF markers tested and with erythrocyte sedimentation rate and serum levels of C-reactive protein and fibrinogen. CONCLUSION: Increased MMP-3 levels in SF are found in inflammatory arthropathies and are not specific for erosive joint diseases. MMP-3 in SF is therefore a potential candidate for the assessment of the inflammatory process in joints. However, the exclusive determination of the active form could indicate the degree of joint destruction.

Adult↗

Matrix metalloproteinase-3 serum levels are correlated with disease activity and predict clinical response in rheumatoid arthritis.

OBJECTIVE: To demonstrate that serum matrix metalloproteinase-3 (MMP-3) is a variable associated with disease activity and with the response to treatment in rheumatoid arthritis (RA). METHODS: Serum MMP-3 levels were measured and compared to biological and clinical disease activity variables in 20 patients with active RA assessed serially during a one year prospective open label trial with methotrexate or tenidap. RESULTS: MMP-3 levels were significantly correlated with C-reactive protein (CRP) and interleukin 6 serum levels as well as with the disease activity score (DAS), not only at start in untreated patients but also during the 12 month followup period in both treated groups. Early changes (after 0.5, 1, 2, or 3 months) in MMP-3 levels were significantly associated with change in DAS observed 4 to 6 months later. CONCLUSION: In addition to CRP, a systemic marker of inflammation, serum MMP-3 may serve as a consistent synovial derived marker of RA disease activity, early changes of which predict disease outcome.

Anti-Inflammatory Agents, Non-Steroidal↗

[The non-recommendations in the treatment of osteoarthritis and rheumatoid arthritis, or why is evidence-based medicine so difficult (still) to apply to rheumatology?].

The speed with which the phrase "Evidence-Based Medicine" has entered our language has been astonishing. Virtually all medical areas are concerned, but it probably applies best when clearcut diagnosis can be made or when mortality or well-defined morbidity are the outcomes, two conditions not really frequently encountered in rheumatology. We will discuss why rheumatology is probably not ready yet for the concept and will systematically review why "Evidence-Based Medicine" could in fact be "evidence-biased medicine". We will emphasize why evidence-based medicine can not replace the personal experience and knowledge of patients, two major corner-stones in the clinician's daily work, but should simply be an access to scientific data for the benefit of both patient and physician.

Arthritis, Rheumatoid↗

Increased synovial fluid levels of interleukin-12, sCD25 and sTNF-RII/sTNF-RI ratio delineate a cytokine pattern characteristic of immune arthropathies.

The assessment of cytokines and their soluble receptors in the synovial fluid (SF) of inflammatory arthropathies may be useful in studying pathogenetic and immunoregulatory mechanisms underlying different diseases. The aim of this work was to study the cytokine network occurring in inflammatory arthropathies and to identify a cytokine profile which is characteristic of an immune-mediated synovitis. Levels of IL-12, as well as IL-4, IL-8, IL-10, IFN-gamma, sCD25, TNF-alpha and its soluble receptors were measured in the SF of various arthropathies, i.e. non-inflammatory arthropathies: "control" meniscus pathology (n = 21), osteoarthritis (n = 22) and chronic crystal arthritis (n = 9); a non-immune inflammatory arthropathy: acute crystal arthritis (n = 11); 2 immune inflammatory arthropathies: reactive arthritis (ReA) (n = 23) and rheumatoid arthritis (RA) (n = 44). SF levels of IL-10, TNF-alpha and sTNF-RII were found to be increased in the three inflammatory arthropathies compared to the "control" meniscus group. Within the inflammatory group, acute crystal arthritis was characterized by a significantly higher sTNF-RI/TNF-alpha ratio and ReA by a significantly lower sTNF-RII/TNF-alpha ratio compared to the two other diseases. The two immune arthropathies, RA and ReA, were characterized by increased SF levels of IL-12, sCD25 and of the sTNF-RII/sTNF-RI ratio. ReA differed however from RA by showing lower IL-8 and IL-4 levels, higher IFN-gamma levels and a higher IL-12/IL-10 ratio, suggesting a more prevalent Th1 profile in ReA SF. Our data indicate that the measurement of SF cytokines and soluble receptors may discriminate between each inflammatory arthropathy and might be useful in clinical practice.

Adult↗

The frequency of cutaneous vasculitis is not increased in patients with rheumatoid arthritis treated with methotrexate.

OBJECTIVE: To analyse the frequency, type, and immunohistological features of clinical cutaneous vasculitis developing in patients with rheumatoid arthritis (RA) treated or not with methotrexate as well as their demographic, clinical and biological characteristics. METHODS: Ninety-one patients with RA receiving 9.5 mg/wk of methotrexate (MTX) were compared for an average observation time of 18 months to 130 matched patients with RA treated with various drugs excluding MTX. RESULTS: Whether receiving MTX or not, 5.4% of patients with RA developed a clinical cutaneous vasculitis. There were significant differences between both groups for 2 variables only: a higher percentage of polyneuropathies and a higher level of immune complex-plasma levels in non-MTX patients. The immunohistological analysis did not differentiate both groups. CONCLUSION: The percentage of cutaneous vasculitis that developed under MTX therapy was not different from that occurring as a natural complication of longstanding severe RA.

Adult↗

The use of Sandimmun (cyclosporin A) in severe refractory rheumatoid arthritis: the Belgian experience.

OBJECTIVE: To investigate practicability, efficacy and tolerability of low starting doses of Sandimmun (cyclosporin A) (2.5 mg/kg daily) in patients with severe refractory rheumatoid arthritis in the short (6 months) and middle (12 months) term. METHODS: Fifty-nine patients, presenting with active and severe rheumatoid arthritis unresponding to conventional DMRADs were allowed to start Sandimmun at the dose of 2.5 mg/kg daily. This dose was progressively increased by steps of 25 mg daily up to a maximum of 5 mg/kg daily according to the renal function and blood pressure. RESULTS: A mean maintenance dose of 3.9 mg/kg daily was reached after 5 months and maintained throughout the study. Twenty-one patients (36%) completed the one year study. The reasons for discontinuation were: inefficacy (13), adverse events (17), both inefficacy and adverse events (5) and non-compliance (3). For those patients who completed the trial, clinical relevant improvements were observed within 3 months of treatment and were maintained until the end of the study for the Lee functional and the Ritchie articular index, as well as for the number of tender and swollen joints. No changes for the grip strength, the biological and immunological parameters were observed. Mean serum creatinine values rose from 0.81 mg/dl at start to 1.1 mg/dl after 5 months of therapy and remained at that level throughout the study. In patients who discontinued, the serum creatinine level nearly normalized after one month of Sandimmun withdrawal. One hundred and sixty-two side effects were reported of which most were minor and known to occur with Sandimmun. Twenty-two cases (37% of patients) dropped out for adverse events before 1 year treatment. The criteria to withdraw the patients from the study differed greatly from centre to centre. CONCLUSIONS: Managing RA patients presenting with very long and severe disease remains difficult. Therefore low dose Sandimmun (2.5-5 mg/kg daily) appears to be a valuable therapeutic opportunity in RA patients refractory to various other conventional drugs, including methotrexate.

Adolescent↗

Low-dose methotrexate: an effective corticosteroid-sparing agent in the musculoskeletal manifestations of sarcoidosis.

Extrapulmonary sarcoidosis, and particularly the presence of musculoskeletal complications of the disease, may require chronic corticosteroid therapy. In five patients with biopsy-proven sarcoidosis and presenting recalcitrant forms of the disease, we introduced low-dose oral methotrexate (MTX) [10 mg/week (7.5-15)] for 30 months (16-34) to control the clinical and biological symptoms as well as to try to reduce the intolerated steroid posology. Beneficial effects were observed within 8-12 weeks in all patients, which allowed a reduction of 59% (35-75) of the corticosteroid posology, and maintained with a follow-up of 3 yr in 4/5 patients. No significant toxicity was observed. MTX appears to be an efficient, safe and corticosteroid-sparing therapeutic agent for the treatment of recalcitrant musculoskeletal manifestations of sarcoidosis.

Administration, Oral↗