References of "Malaise, Michel"
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See detailIntermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind, multicenter study versus placebo
Uebelhart, D.; Malaise, Michel ULg; Marcolongo, R. et al

in Osteoarthritis and Cartilage (2004), 12(4), 269-276

Objective: To investigate the efficacy and tolerability of a 3-month duration, twice a-year, intermittent treatment with oral chondroitin sulfate (CS) in knee osteoarthritis (OA) patients. Design: A total ... [more ▼]

Objective: To investigate the efficacy and tolerability of a 3-month duration, twice a-year, intermittent treatment with oral chondroitin sulfate (CS) in knee osteoarthritis (OA) patients. Design: A total of 120 patients with symptomatic knee OA were randomized into two groups receiving either 800 mg CS or placebo (PBO) per day for two periods of 3 months during 1 year. Primary efficacy outcome was Lequesne's algo-functional index (AFI); secondary outcome parameters included VAS, walking time, global judgment, and paracetamol consumption. Radiological progression was assessed by automatic measurement of medial femoro-tibial joint space width on weight-bearing X-rays of both knees. Clinical and biological tolerability was assessed. Results: One hundred and ten of 120 patients were included in the ITT analysis. AFI decreased significantly by 36% in the CS group after 1 year as compared to 23% in the PBO group. Similar results were found for the secondary outcomes parameters. Radiological progression at month 12 showed significantly decreased joint space width in the PBO group with no change in the CS group. Tolerability was good with only minor adverse events identically observed in both groups. Conclusion: This study provides evidences that oral CS decreased pain and improved knee function. The 3-month intermittent administration of 800 mg/day of oral CS twice a year does support the prolonged effect known with symptom-modifying agents for OA. The inhibitory effect of CS on the radiological progression of the medial femoro-tibial joint space narrowing could suggest further evidence of its structure-modifying properties in knee OA. (C) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved. [less ▲]

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See detailTherapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial
Klareskog, L.; van der Heijde, D.; de Jager, J. P. et al

in Lancet (2004), 363(9410), 675-681

Background Etanercept and methotrexate are effective in the treatment of rheumatoid arthritis but no data exist on concurrent initiation or use of the combination compared with either drug alone. We aimed ... [more ▼]

Background Etanercept and methotrexate are effective in the treatment of rheumatoid arthritis but no data exist on concurrent initiation or use of the combination compared with either drug alone. We aimed to assess combination treatment with etanercept and methotrexate versus the monotherapies in patients with rheumatoid arthritis. Methods In a double-blind, randomised, clinical efficacy, safety, and radiographic study, 686 patients with active rheumatoid arthritis were randomly allocated to treatment with etanercept 25 mg (subcutaneously twice a week), oral methotrexate (up to 20 mg every week), or the combination. Clinical response was assessed by criteria of the American College of Rheumatology (ACR). The primary efficacy endpoint was the numeric index of the ACR response (ACR-N) area under the curve (AUC) over the first 24 weeks. The primary radiographic endpoint was change from baseline to week 52 in total joint damage and was assessed with the modified Sharp score. Analysis was by intention to treat. Findings Four patients did not receive any drug; thus 682 were studied. ACR-N AUC at 24 weeks was greater for the combination group compared with etanercept alone and methotrexate alone (18.3% years [95% CI 17.1-19.6] vs 14.7%-years [13.5-16.0], p<0.0001, and 12.2%-years [11.0-13.4], p<0.0001; respectively). The mean difference in ACR-N AUC between combination and methotrexate alone was 6.1 (95% CI 4.5-7.8, p<0.0001) and between etanercept and methotrexate was 2.5 (0.8-4.2, p=0.0034). The combination was more efficacious than methotrexate or etanercept alone in retardation of joint damage (mean total Sharp score -0.54 [95% CI -1.00 to -0.07] vs 2.80 [1.08 to 4.51], p<0.0001, and 0.52 [-0.10 to 1.15], p=0.0006; respectively). The mean difference in total Sharp score between combination and methotrexate alone was -3.34 (95% CI -4.86 to -1.81, p<0.0001) and between etanercept and methotrexate was -2.27 (-3.81 to -0.74, p=0.0469). The number of patients reporting infections or adverse events was similar in all groups. Interpretation The combination of etanercept and methotrexate was significantly better in reduction of disease activity, improvement of functional disability, and retardation of radiographic progression compared with methotrexate or etanercept alone. These findings bring us closer to achievement of remission and repair of structural damage in rheumatoid arthritis. [less ▲]

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See detail15-deoxy-delta12,14-prostaglandin J2 inhibits Bay 11-7085-induced sustained extracellular signal-regulated kinase phosphorylation and apoptosis in human articular chondrocytes and synovial fibroblasts
Relic, Biserka ULg; Benoit, Valerie; Franchimont, Nathalie et al

in Journal of Biological Chemistry (2004), 279(21), 399-403

We have previously shown that nuclear factor-kappaB inhibition by adenovirus expressing mutated IkappaB-alpha or by proteasome inhibitor increases human articular chondrocytes sensibility to apoptosis ... [more ▼]

We have previously shown that nuclear factor-kappaB inhibition by adenovirus expressing mutated IkappaB-alpha or by proteasome inhibitor increases human articular chondrocytes sensibility to apoptosis. Moreover, the nuclear factor-kappaB inhibitor BAY11-7085, a potent anti-inflammatory drug in rat adjuvant arthritis, is itself a proapoptotic agent for chondrocytes. In this work, we show that BAY 11-7085 but not the proteasome inhibitor MG-132 induced a rapid and sustained phosphorylation of extracellular signal-regulated kinases (ERK1/2) in human articular chondrocytes. The level of ERK1/2 phosphorylation correlated with BAY 11-7085 concentration and chondrocyte apoptosis. 15-Deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) and its precursor prostaglandin (PG) D2 but not PGE2 and PGF2alpha rescued chondrocytes from BAY 11-7085-induced apoptosis. 15d-PGJ2 markedly inhibited BAY 11-7085-induced phosphorylation of ERK1/2. BAY 11-7085 also induced ERK1/2 phosphorylation and apoptosis in human synovial fibroblasts, and these reactions were down-regulated by 15d-PGJ2. Further analysis in synovial fibroblasts showed that only molecules that suppressed BAY 11-7085-induced phosphorylation of ERK1/2 (i.e. 15d-PGJ2, PGD2, and to a lesser extent, MEK1/2 inhibitor UO126, but not prostaglandins E2 and F2alpha or peroxisome proliferator-activated receptor-gamma agonist ciglitazone) were able protect cells from apoptosis. These results suggested that the antiapoptotic effect of 15d-PGJ2 on chondrocytes and synovial fibroblasts might involve inhibition of ERK1/2 phosphorylation. [less ▲]

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See detailLe medicament du mois. Etoricoxib (Arcoxia)
Leclercq, P.; Malaise, Michel ULg

in Revue Médicale de Liège (2004), 59(5), 345-349

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 ... [more ▼]

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. [less ▲]

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See detailFièvre méditerranéenne familiale
Leclercq, P.; Hermesse, A.; Malaise, Michel ULg

in Revue Médicale de Liège (2004), 59(5), 320-325

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 ... [more ▼]

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. [less ▲]

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See detailLa goutte
Leclercq, P.; Malaise, Michel ULg

in Revue Médicale de Liège (2004), 59(5), 274-280

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 ... [more ▼]

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. [less ▲]

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See detailLe medicament du mois. Valdecoxib (Bextra)
Scheen, André ULg; Malaise, Michel ULg

in Revue Médicale de Liège (2004), 59(4), 251-254

Valdecoxib (Bextra tablets of 10 mg and 20 mg) is a new non steroidal antiinflammatory drug (NSAID) that selectively inhibits COX-2 isoform of cyclo-oxygenase. It is indicated for the symptomatic ... [more ▼]

Valdecoxib (Bextra tablets of 10 mg and 20 mg) is a new non steroidal antiinflammatory drug (NSAID) that selectively inhibits COX-2 isoform of cyclo-oxygenase. It is indicated for the symptomatic treatment of osteoarthritis or rheumatoid arthritis (10 to 20 mg once a day) and for the treatment of primary dysmenorrhea (40 mg once a day). Valdecoxib is as efficacious as conventional non-COX-2 selective NSAIDs, but offers the advantage of a much better gastrointestinal tolerance. Valdecoxib has a prodrug that can be administered intravenously or intramuscularly (parecoxib, Dynastat) and has been developed for the short-term treatment of postsurgical pain. [less ▲]

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See detailRaloxifene protects Osteoblasts from apoptosis induced by sodium nitroprusside: Potential involvement of ceramide
Olivier, Sabine ULg; Fillet, Marianne ULg; Malaise, Michel ULg et al

in Journal of Bone and Mineral Research (2003, September), 18(Suppl. 2), 136

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See detailIdentification of the signalling pathways required for interleukin-1 beta stimulation of osteoprotegerin synthesis in osteoblastic cells
Lambert, Cecile; Ribbens, Clio ULg; Bours, Vincent ULg et al

in Journal of Bone and Mineral Research (2003, September), 18(Suppl. 2), 142

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See detailInterleukin-1beta and tumor necrosis factor-alpha enhance the shedding of Interleukin-6 receptor in osteoblastic cells: Involvement of tumor necrosis factor-alpha converting enzyme
Franchimont, N. M.; Lambert, Cecile; Ribbens, Clio ULg et al

in Arthritis and Rheumatism (2003, September), 48(9, Suppl. S), 482

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See detailRheumatoid hand joint synovitis: gray-scale and power Doppler US quantifications following anti-tumor necrosis factor-alpha treatment: pilot study
Ribbens, Clio ULg; Andre, Béatrice ULg; Marcelis, Stefaan et al

in Radiology (2003), 229(2), 562-569

PURPOSE: To evaluate by using B-mode and power Doppler ultrasonography (US) and clinical assessment the response of hand joint synovitis in patients with active rheumatoid arthritis (RA) to treatment with ... [more ▼]

PURPOSE: To evaluate by using B-mode and power Doppler ultrasonography (US) and clinical assessment the response of hand joint synovitis in patients with active rheumatoid arthritis (RA) to treatment with the anti-tumor necrosis factor-alpha agent infliximab. MATERIALS AND METHODS: Wrists, metacarpophalangeal (MCP) joints, and proximal interphalangeal (PIP) joints in 11 patients with active RA were assessed before and 6 weeks after three infliximab infusions. US assessment was performed at a single site in the MCP and PIP joints and at two sites (radiocarpal and intercarpal) in the wrists. Twenty measurements were performed in the wrists; 110 measurements, in the MCP joints; and 103 measurements, in the PIP joints. Two wrists and seven PIP joints were excluded owing to complete joint destruction. US parameters (synovial thickness, number of US-positive joints [ie, with synovial thickness > or = 1 mm], cumulative synovial thickness index, and presence of Doppler signal) and clinical parameters (swollen joint count) were independently assessed and compared with baseline values by using the McNemar chi2 and paired Student t tests. RESULTS: After infliximab treatment, there was a significant decrease in the mean numbers of swollen and US-positive joints and in the cumulative synovial thickness (P <.05). The mean synovial thickness decreased in all joints swollen at baseline and in the MCP and PIP joints not swollen at baseline (P <.01). Change from baseline cumulative synovial thickness correlated significantly with change in disease activity score (r = 0.69, P <.05). The number of positive Doppler US signals decreased significantly (in 13 US-positive joints at baseline, in five after treatment; P <.05). CONCLUSION: US is a feasible imaging modality for measurement of the response of RA small-joint synovitis to therapy. [less ▲]

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See detailEfficacy 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
van de Putte, L. B. A.; Rau, R.; Breedveld, F. C. et al

in Annals of the Rheumatic Diseases (2003), 62(12), 1168-1177

OBJECTIVES: To evaluate efficacy, dose response, safety, and tolerability of adalimumab (D2E7) in disease modifying antirheumatic drug (DMARD) refractory patients with longstanding, active rheumatoid ... [more ▼]

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. [less ▲]

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See detailCytokine production from sputum cells after allergenic challenge in IgE-mediated asthma
Bettiol, Jeanne; Sele, Jocelyne ULg; Henket, Monique ULg et al

in Allergy (2002), 57(12), 1145-1150

Background: Th2 cytokine production from airway cells is thought to govern the eosinophilic airways in ammation in allergic asthma. Induced sputum has become a widely used technique to assess airways in ... [more ▼]

Background: Th2 cytokine production from airway cells is thought to govern the eosinophilic airways in ammation in allergic asthma. Induced sputum has become a widely used technique to assess airways in ammation. Methods: By applying the technique of induced sputum to collect airways cells, we have assessed the spontaneous production of a set of cytokines, including interleukin-4, 6, 10, interferon-gamma and tumour necrosis factor-alpha 6 h after a bronchial allergenic hallenge with Dermatophagoides pteronyssinus (Dpt) in 12 sensitized asthmatics and compared the results obtained after inhalation of saline as control. A group of eight healthy non-allergic subjects was enrolled to control for any non-specific effect of Dpt. Cytokines were measured by a dynamic immunoassay during a 24-h sputum cell culture. Results: Allergen challenge in sensitized asthmatics caused an acute and a late bronchospasm together with a rise in sputum eosinophil counts. Afterwards allergen sputum cells from allergic asthmatics displayed a rise in their production of IL-4 (P < 0.01), IL-6 (P < 0.05) and IL- 10 (P < 0.05) when compared to saline. By this time sputum generation of IL- 4 in atopic asthmatics was greater than in healthy subjects (P < 0.001). Furthermore, in allergic asthmatics there was a strong correlation between the rise in interleukin-4 production from sputum cells and the rise in sputum eosinophils (r = 0.87, P < 0.001). Conclusions: Sputum cell culture is a useful model to assess cytokine production in allergic asthmatics who show a marked up-regulation of Th2 cytokines following acute allergen exposure. The rise in sputum eosinophil count following allergen challenge strongly correlates with the rise in IL-4 generation from sputum cells. [less ▲]

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See detailA positive response to infliximab in Crohn disease: Association with a higher systemic inflammation before treatment but not with-308 TNF gene polymorphism
Louis, Edouard ULg; Vermeire, S.; Rutgeerts, P. et al

in Scandinavian Journal of Gastroenterology (2002), 37(7), 818-824

Background: Two-thirds to three-fourths of patients with either refractory luminal or fistulizing Crohn disease respond to infliximab treatment. The ability or inability to respond seems to persist over ... [more ▼]

Background: Two-thirds to three-fourths of patients with either refractory luminal or fistulizing Crohn disease respond to infliximab treatment. The ability or inability to respond seems to persist over time. Biological characteristics and/or genetic background can influence the response to treatment. The aim was to assess the value of C-reactive protein and TNF-alpha serum levels before treatment as well as the TNF -308 gene polymorphism in the prediction of response to infliximab treatment in Crohn disease. Methods: Two-hundred-and-twenty-six Crohn disease patients treated in the setting of an expanded access programme to infliximab in Belgium were studied. There were 136 refractory luminal diseases and 90 refractory fistulizing diseases. Luminal diseases were treated with one single infusion; fistulizing diseases with three infusions at weeks 0, 2 and 6. A clinical response to treatment was defined as either a Crohn disease activity index <150 (complete) or a drop of 70 points (partial) at week 4, for luminal disease, and as either complete fistula healing (complete) or a decrease of at least 50% of the number of draining fistulas on two consecutive visits between weeks 0 and 18, for fistulizing disease. CRP and serum TNF-α levels were measured at week 0 before treatment and were compared between responders and non- responders. Patients were genotyped for the -308 TNF gene polymorphism, and allelic as well as genotype frequencies were compared between responders and non- responders. Results: There were 73.2% responders (46.4% complete and 26.8% partial) and 26.8% non- responders. Response rates were similar in luminal and fistulizing diseases. CRP level before treatment was significantly higher in responders than in non-responders (16.8 mg/l (5-160) versus 9.6 mg/l (5-143); P = 0.02). Furthermore, response rate was significantly higher in patients with elevated CRP (> 5 mg/l) than in patients with a normal CRP value (< 5 mg/l) before treatment (76% versus 46%; P = 0.004; OR: 0.26 (0.11-0.63)). Allelic and genotype frequencies for -308 TNF gene polymorphis m were not significantly different between responders and non- responders - with the exception of a slightly higher TNF2 frequency in nonresponders in luminal disease (22.1% versus 11.6%; P = 0.04). However, this was not associated with a significant difference in genotype frequencies. Conclusion: A positive clinical response to infliximab was associated with a higher CRP level before treatment in our population of Crohn disease patients, but there was no relevant association with -308 TNF gene polymorphism. We therefore suggest that CRP level may help to identify better candidates for infliximab treatment. [less ▲]

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See detailMaladie de Horton et atteintes artérielles extra-temporales: utilité de la tomographie par émission de positons au 18FDG. A propos de trois observations et d’une revue de la littérature.
Belhocine, Tarik; Kaye, Olivier; Delanaye, Pierre ULg et al

in Revue de Médecine Interne (2002), 23(7), 584-591

Increased glucose metabolism detected by (18)FDG PET imaging in unsuspected extra-temporal vessels locations of Horton's disease. Clinical observations and review of literature. Purpose. - We report three ... [more ▼]

Increased glucose metabolism detected by (18)FDG PET imaging in unsuspected extra-temporal vessels locations of Horton's disease. Clinical observations and review of literature. Purpose. - We report three cases of Horton's disease, in which F18-Fluorine-2-Deoxy-D-Glucose ((18)FDG) positron emission tomography (PET) demonstrated a clinically unsuspected extra-cranial vessels hypermetabolism. Methods. - Fully corrected whole-body PET was performed in three patients (two women, one man) for exploring a marked inflammatory syndrome. Scanning was acquired 60 min after i.v. injection of 222 MBq of (18)FDG in average. Results. - In two patients with histologically proven Horton's disease, PET alone showed increased glucose metabolism involving the carotid and sub-clavian arteries as well as the ascending aorta, aortic arch, thoracic and abdominal aorta, and the iliac and femoral arteries. In the third patient, by detecting cervical, thoracic and abdominal vessel hypermetabolism, PET non-invasively contributed to the diagnosis of giant cell arteritis. All patients had complete clinical and biological response to corticoids. PET controls performed 3- to 6-months post-treatment, confirmed the disappearance of the metabolic stigma. Conclusion. - (18)FDG PET may show an increased glucose metabolism in asymptomatic extra-cranial vessels locations of Horton's arteritis. If these observations are confirmed on controlled trials, PET could be particularly useful for non-invasive diagnosing, staging and monitoring atypical clinical forms of Horton's disease. The metabolic imaging could also contribute to a better understanding of the pathogenesis of GCA. (C) 2002 Editions scientifiques et medicales Elsevier SAS. [less ▲]

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See detailMaladie de Horton et atteintes arterielles extratemporales: utilite de la tomographie par emission de positons au 18FDG. A propos de trois observations et d'une revue de la litterature
Belhocine, T.; Kaye, O.; Delanaye, Pierre ULg et al

in Revue de Médecine Interne (2002), 23(7), 584-91

PURPOSE: We report three cases of Horton's disease, in which F18-Fluorine-2-Deoxy-D-Glucose (18FDG) positron emission tomography (PET) demonstrated a clinically unsuspected extra-cranial vessels ... [more ▼]

PURPOSE: We report three cases of Horton's disease, in which F18-Fluorine-2-Deoxy-D-Glucose (18FDG) positron emission tomography (PET) demonstrated a clinically unsuspected extra-cranial vessels hypermetabolism. METHODS: Fully corrected whole-body PET was performed in three patients (two women, one man) for exploring a marked inflammatory syndrome. Scanning was acquired 60 min after i.v. injection of 222 MBq of 18FDG in average. RESULTS: In two patients with histologically proven Horton's disease, PET alone showed increased glucose metabolism involving the carotid and sub-clavian arteries as well as the ascending aorta, aortic arch, thoracic and abdominal aorta, and the iliac and femoral arteries. In the third patient, by detecting cervical, thoracic and abdominal vessel hypermetabolism, PET non-invasively contributed to the diagnosis of giant cell arteritis. All patients had complete clinical and biological response to corticoids. PET controls performed 3- to 6-months post-treatment, confirmed the disappearance of the metabolic stigma. CONCLUSION: 18FDG PET may show an increased glucose metabolism in asymptomatic extracranial vessels locations of Horton's arterities. If these observations are confirmed on controlled trials, PET could be particularly useful for non-invasive diagnosing, staging and monitoring atypical clinical forms of Horton's disease. The metabolic imaging could also contribute to a better understanding of the pathogenesis of GCA. [less ▲]

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See detailTNF-alpha protects human primary articular chondrocytes from nitric oxide-induced apoptosis via nuclear factor-kappaB
Relic, Biserka ULg; Bentires-Alj, Mohamed; Ribbens, Clio ULg et al

in Laboratory Investigation : Journal of Technical Methods & Pathology (2002), 82(12), 1661-1672

TNF-alpha plays a key role in rheumatoid arthritis, but its effect on chondrocyte survival is still conflicting. In the present study, we tested how TNF-alpha influences chondrocyte survival in response ... [more ▼]

TNF-alpha plays a key role in rheumatoid arthritis, but its effect on chondrocyte survival is still conflicting. In the present study, we tested how TNF-alpha influences chondrocyte survival in response to nitric oxide (NO)-related apoptotic signals, which are abundant during rheumatoid arthritis. Human primary articular chondrocytes or cartilage explants were pretreated with TNF-alpha for 24 hours and then treated with the proapoptotic NO donor sodium-nitro-prusside (SNP) for an additional 24 hours. TNF-alpha pretreatment markedly protected chondrocytes from SNP-induced cell death. Preincubation of chondrocytes with TNF-alpha inhibited both SNP-induced high-molecular weight DNA fragmentation and annexin V-FITC binding. Of interest, TNF-alpha induced persistent nuclear factor-kappaB (NF-kappaB)-DNA binding activity even in the presence of SNP, mirroring apoptosis protection effects. Both the TNF-alpha antiapoptotic effect and NF-kappaB-DNA binding activity were significantly inhibited by NF-kappaB inhibitors, Bay 11-7085, MG-132, and adenovirus-expressing mutated IkappaB-alpha. Phosphatidylinositol-3 kinase inhibitor LY 294002 also markedly inhibited the antiapoptotic effect of TNF-alpha. In primary chondrocytes, TNF-alpha induced expression of the antiapoptotic protein Cox-2, which persisted in the presence of SNP, and a specific Cox-2 inhibitor significantly blocked the TNF-alpha protective effect. We therefore conclude that TNF-alpha-mediated protection of chondrocytes from NO-induced apoptosis acts through NF-kappaB and requires Cox-2 activity. [less ▲]

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See detailDynamic T cell receptor clonotype changes in synovial tissue of patients with early rheumatoid arthritis: effects of treatment with cyclosporin A (Neoral)
VanderBorght, Ann; De Keyser, Filip; Geusens, Piet et al

in Journal of Rheumatology (2002), 29(3), 416-426

OBJECTIVE: To study T cell receptor (TCR) repertoire changes in synovial membrane over a 16 week period in patients with early rheumatoid arthritis (RA); and to study the influence of cyclosporin A (CSA ... [more ▼]

OBJECTIVE: To study T cell receptor (TCR) repertoire changes in synovial membrane over a 16 week period in patients with early rheumatoid arthritis (RA); and to study the influence of cyclosporin A (CSA) on TCR repertoire in a subgroup of these patients. METHODS: Synovial tissue biopsies and paired blood samples were obtained from 12 patients with early RA at 2 time points. Seven patients were treated with CSA (Neoral-Sandimmun, 3 mg/kg/day) and 5 patients with placebo for 16 weeks. TCR V gene repertoires were analyzed by semiquantitative PCR-ELISA. CDR3 spectratyping and sequence analysis was used to compare TCR clonotype distributions. RESULTS: TCR-specific mRNA was detected in all synovial tissue biopsies at the first sampling, but in only 8/12 biopsies 16 weeks later (4/7 CSA group, 4/5 placebo group). Overrepresented TCR BV genes were found in biopsies of 10/12 patients at the first time point, and in 7/12 patients after 16 weeks (3/7 CSA, 4/5 placebo). CDR3 sequence analysis revealed dynamic repertoire changes with only a few persisting clonotypes in the synovial tissue of placebo controls. Persisting T cell clonotypes were more frequently found in the synovial tissue of CSA treated patients compared to the placebo group. CONCLUSION: These data suggest a dynamic process of T cell recruitment in the joints of RA patients. This process, possibly due to activation and subsequent infiltration of new T cell clones, apparently is influenced by CSA treatment. Synovial tissue T cells were no longer detected after 16 weeks' CSA treatment in 3 patients. In the other CSA treated patients, new T cell clones infiltrated, while other clones were persistently represented in the joints. These data may have important consequences for the design of T cell targeted therapies for RA. [less ▲]

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See detailDéminéralisation et ostéoporose: une confusion sémantique
Kaiser, Marie-Joëlle ULg; Malaise, Michel ULg

in Revue Médicale de Liège (2002), 57(5), 274-279

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 ... [more ▼]

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. [less ▲]

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See detailComment je traite ... une polyarthrite rhumatoïde. L'avènement d'une nouvelle ère thérapeutique: les anticorps anti-TNF-alpha
Kaiser, Marie-Joëlle ULg; Malaise, Michel ULg

in Revue Médicale de Liège (2002), 57(8), 486-492

Rheumatoid arthritis (RA) is the most frequent autoimmune inflammatory arthropathy. Chronic synovial inflammation usually results in cartilage destruction, bone erosion and subsequent joint deformities ... [more ▼]

Rheumatoid 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. [less ▲]

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