Biomedical subjects

M Malaise

Publications and source records attributed to M Malaise.

At least 19 recordsLinked to original sources

PubMed2006

A prospective randomised multicentre study comparing continuous and intermittent treatment with celecoxib in patients with osteoarthritis of the knee or hip.

OBJECTIVE: To compare the effects of continuous and intermittent celecoxib treatment in patients with knee or hip osteoarthritis in flare. METHODS: In this 24-week, prospective, randomised, double-blind, placebo-controlled study, patients were randomly assigned to receive continuous (n = 62) or intermittent (n = 61) treatment with celecoxib 200 mg once daily. The primary efficacy end point was the area under the curve (AUC) of the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total scores between baseline and week 24 divided by the time interval. Secondary end points included the percentage of days with intake of the flare drug, the AUC of the change in the WOMAC total scores, the mean change from baseline in the WOMAC scores, and the patient's and physician's global assessment of osteoarthritis. RESULTS: There were no significant differences between patients randomised to continuous or intermittent treatment in the primary end point or most of the secondary end points, although a consistent trend supporting continuous treatment was observed. The percentage of days with intake of the flare drug was significantly lower (p = 0.031) in the group receiving continuous versus intermittent celecoxib. Both treatment regimens were well tolerated. CONCLUSION: The results of this pilot study indicate a potential clinical difference between continuous and intermittent treatment with celecoxib, and may be useful in designing future trials. A larger trial on both efficacy and safety outcomes is required for conclusive evidence in favour of either continuous or intermittent treatment.

Aged↗

PubMed2006

A long-term, open-label trial of the safety and efficacy of etanercept (Enbrel) in patients with rheumatoid arthritis not treated with other disease-modifying antirheumatic drugs.

OBJECTIVE: To evaluate the long-term safety and efficacy of etanercept in patients with rheumatoid arthritis. METHODS: 549 patients entered this 5-year, open-label extension study and received etanercept 25 mg twice weekly. All patients showed inadequate responses to disease-modifying antirheumatic drugs before entry into the double-blind studies. Safety assessments were carried out at regular intervals. Primary efficacy end points were the numbers of painful and swollen joints; secondary variables included American College of Rheumatology (ACR) response rate, Disease Activity Score and acute-phase reactants. Efficacy was analysed using the last-observation-carried-forward approach. RESULTS: Of the 549 patients enrolled in the open-label trial, 467 (85%), 414 (75%) and 371 (68%) completed 1, 2 and 3 years, respectively; 363 (66%) remained in the study at the time of this analysis. A total exposure of 1498 patient-years, including the double-blind study, was accrued. In the open-label trial, withdrawals for efficacy-related and safety-related reasons were 11% and 13%, respectively. Frequent adverse events included upper respiratory infections, flu syndrome, rash and injection-site reactions. Rates of serious infections and malignancies remained unchanged over the course of the study; there were no reports of patients with central demyelinating disease or serious blood dyscrasias. After 3 years, ACR20, ACR50 and ACR70 response rates were 78%, 51% and 27%, respectively. The Disease Activity Score score was reduced to 3.0 at 3 months and 2.6 at 3 years from 5.1. A sustained improvement was found in Health Assessment Questionnaire scores throughout the 3-year time period. CONCLUSION: After 3 years of treatment, etanercept showed sustained efficacy and a favourable safety profile.

Antirheumatic Agents↗

PubMed2005

Healthcare consumption and direct costs of rheumatoid arthritis in Belgium.

The aim of this study was to compare the socioeconomic consequences of early and late rheumatoid arthritis in Belgium and to assess the patient out-of-pocket contributions. This multicentre longitudinal study in Belgium evaluated patients with rheumatoid arthritis. Early disease was defined as diagnosis since less than 1 year. At baseline sociodemographic and disease characteristics were assessed and during the following year patients recorded all healthcare- and non-healthcare-related direct costs and out-of-pocket contributions. The study included 48 patients with early and 85 patients with late rheumatoid arthritis. Mean disease duration was 0.5 vs 12.5 years in patients with early and late rheumatoid arthritis, respectively. The disease activity score (DAS28) was comparable between both groups (4.1 vs 4.5, p = 0.14), but physical function (Health Assessment Questionnaire, HAQ) was more impaired in patients with long-standing disease (1.0 vs 1.7, p < 0.001). Work disability had increased from 2% in patients with early to 18% in patients with late disease. The annual societal direct costs per patient were 3055 Euros (median: 1518 Euros) opposed to 9946 Euros (median: 4017 Euros) for early and late rheumatoid arthritis, respectively. The higher direct cost for patients with long-standing disease was seen for all categories, but especially for physiotherapy and need for devices and adaptations. Patients with early as well as late disease contribute out of pocket about one-third to the direct healthcare costs. Within each group, HAQ was a strong determinant of costs. In Belgium, patients with long-standing rheumatoid arthritis are nine times more likely to be work disabled than patients with less than 1 year disease duration and have a threefold increase in costs. Differences in healthcare consumption between patients could be mainly explained by differences in physical function (HAQ).

Adult↗

PubMed2005

EULAR report on the use of ultrasonography in painful knee osteoarthritis. Part 1: prevalence of inflammation in osteoarthritis.

OBJECTIVES: To assess the prevalence of inflammation in subjects with chronic painful knee osteoarthritis (OA), as determined by the presence of synovitis or joint effusion at ultrasonography (US); and to evaluate the correlation between synovitis, effusion, and clinical parameters. METHODS: A cross sectional, multicentre, European study was conducted under the umbrella of EULAR-ESCISIT. SUBJECTS: had primary chronic knee OA (ACR criteria) with pain during physical activity >or=30 mm for at least 48 hours. Clinical parameters were collected by a rheumatologist and an US examination of the painful knee was performed by a radiologist or rheumatologist within 72 hours of the clinical examination. Ultrasonographic synovitis was defined as synovial thickness >or=4 mm and diffuse or nodular appearance, and a joint effusion was defined as effusion depth >or=4 mm. RESULTS: 600 patients with painful knee OA were analysed. At US 16 (2.7%) had synovitis alone, 85 (14.2%) had both synovitis and effusion, 177 (29.5%) had joint effusion alone, and 322 (53.7%) had no inflammation according to the definitions employed. Multivariate analysis showed that inflammation seen by US correlated statistically with advanced radiographic disease (Kellgren-Lawrence grade >or=3; odds ratio (OR)=2.20 and 1.91 for synovitis and joint effusion, respectively), and with clinical signs and symptoms suggestive of an inflammatory "flare", such as joint effusion on clinical examination (OR=1.97 and 2.70 for synovitis and joint effusion, respectively) or sudden aggravation of knee pain (OR=1.77 for joint effusion). CONCLUSION: US can detect synovial inflammation and effusion in painful knee OA, which correlate significantly with knee synovitis, effusion, and clinical parameters suggestive of an inflammatory "flare".

Aged↗

PubMed2005

EULAR report on the use of ultrasonography in painful knee osteoarthritis. Part 2: exploring decision rules for clinical utility.

BACKGROUND: Synovial inflammation (as defined by hypertrophy and effusion) is common in osteoarthritis (OA) and may be important in both pain and structural progression. OBJECTIVE: To determine if decision rules can be devised from clinical findings and ultrasonography (US) to allow recognition of synovial inflammation in patients with painful knee OA. METHODS: A EULAR-ESCISIT cross sectional, multicentre study enrolled subjects with painful OA knee who had clinical, radiographic, and US evaluations. A classification and regression tree (CART) analysis was performed to find combinations of predictor variables that would provide high sensitivity and specificity for clinically detecting synovitis and effusion in individual subjects. A range of definitions for the two key US variables, synovitis and effusion (using different combinations of synovial thickness, depth, and appearance), were also included in exploratory analyses. RESULTS: 600 patients with knee OA were included in the analysis. For both knee synovitis and joint effusion, the sensitivity and specificity were poor, yielding unsatisfactory likelihood ratios (75% sensitivity, 45% specificity, and positive LR of 1.36 for knee synovitis; 71.6% sensitivity, 43.2% specificity, and positive LR of 1.26 for joint effusion). The exploratory analyses did not improve the sensitivity and specificity (demonstrating positive LRs of between 1.26 and 1.57). CONCLUSION: Although it is possible to determine clinical and radiological predictors of OA inflammation in populations, CART analysis could not be used to devise useful clinical decision rules for an individual subject. Thus sensitive imaging techniques such as US remain the most useful tool for demonstrating synovial inflammation of the knee at the individual level.

Adult↗

PubMed2005

A dose adjustment in patients with rheumatoid arthritis not optimally responding to a standard dose of infliximab of 3 mg/kg every 8 weeks can be effective: a Belgian prospective study.

OBJECTIVES: To analyse the effect of a dose increase in patients with severe rheumatoid arthritis (RA) with insufficient clinical response to 3 mg/kg infliximab every 8 weeks. METHODS: Patients suffering from active refractory RA despite methotrexate, were treated with i.v. infusions of infliximab (3 mg/kg) on week 0, 2, 6 and every 8 weeks thereafter. Based on the clinical judgement at week 22, patients received a dose increase of 100 mg from week 30 on. The American College of Rheumatology (ACR) core set for disease activity measures was regularly assessed. RESULTS: Five hundred and eleven RA patients were included. At week 22, 61.4, 34 and 14.1% of all patients met ACR 20, ACR 50 and ACR 70 criteria, respectively, and 6.1% of patients were in remission. A low swollen joint count at baseline was correlated with improvement at week 22 for ACR 20 (P < 0.06), ACR 50 (P < 0.06) and ACR 70 (P < 0.005). The change in HAQ score between weeks 0 and 22 was predictive for response at week 54 (P < 0.01). The dose of infliximab was increased by 100 mg in 22% of the patients. Most baseline values of patients requiring dose increase were higher (P < or = 0.001) than the baseline values of the remaining patients. Increasing the dose of infliximab by one vial from week 30 on could circumvent the partial loss of response in these patients. CONCLUSION: Infliximab use in this large out-patient cohort resulted in a significant clinical improvement. A subgroup that partially lost response during the first 22 weeks could regain response by adding 100 mg of infliximab to the subsequent doses. Due to the current study design, however, a regression to the mean like effect could not be ruled out.

Adult↗

PubMed2004

Rapid improvement of bone metabolism after infliximab treatment in Crohn's disease.

BACKGROUND: Crohn's disease is associated with low bone mineral density and altered bone metabolism. AIM: To assess the evolution of bone metabolism in Crohn's disease patients treated with infliximab. METHODS: We studied 71 Crohn's disease patients treated for the first time with infliximab for refractory Crohn's disease. Biochemical markers of bone formation (type-I procollagen N-terminal propeptide, bone-specific alkaline phosphatase, osteocalcin) and of bone resorption (C-telopeptide of type-I collagen) were measured in the serum before and 8 weeks after infliximab therapy and compared with values in a matched healthy control group. RESULTS: Eight weeks after treatment with infliximab, a normalization of bone markers was observed with a median increase in formation markers of 14-51% according to marker and a lower but significant decrease in resorption marker (median 11%). A clinically relevant increase in bone formation markers was present in 30-61% of patients according to the marker. A clinically relevant decrease in C-telopeptide of type-I collagen was present in 38% of patients. No association was found with any tested demographic or clinical parameter. CONCLUSION: Infliximab therapy in Crohn's disease may rapidly influence bone metabolism by acting either on bone formation or bone resorption. This improvement seems to be independent of clinical response to infliximab.

Adolescent↗

PubMed2004

Increased expression of receptor activator of NF-kappaB ligand (RANKL), its receptor RANK and its decoy receptor osteoprotegerin in the colon of Crohn's disease patients.

Crohn's disease (CD) is associated with low bone mass due to chronic inflammation and other factors. Receptor activator of NF-kappaB ligand (RANKL), its receptor RANK and its decoy receptor osteoprotegerin (OPG) are potentially involved in this process as they regulate osteoclastogenesis and are influenced by pro-inflammatory cytokines. The aim of this study was to determine the levels of soluble RANKL (sRANKL), RANK and OPG expression both in the serum and in the colon of CD patients. Levels of sRANKL and OPG were assessed in the serum and the supernatants of cultured colonic biopsies in patients with CD and controls by ELISA. RANK expression was explored by immunostaining and immunofluorescence of fixed colonic samples. OPG and sRANKL levels were higher in the serum of CD patients as compared to age- and sex-matched controls. Levels of sRANKL and OPG were significantly enhanced in cultured colonic biopsies from CD, and OPG levels correlated with histological inflammation, and pro- and anti-inflammatory cytokine levels. No significant correlation was found for sRANKL. RANK+ cells were increased in the colon of CD, particularly in inflamed areas. These cells were positive for CD68 or S100 protein. We conclude that serum and local levels of sRANKL and OPG are increased in CD. Moreover, RANK is expressed in the colonic mucosa by subpopulations of activated macrophages or dendritic cells at higher levels in CD compared to normal colon.

Adolescent↗

PubMed2004

A randomised placebo controlled 12 week trial of budesonide and prednisolone in rheumatoid arthritis.

OBJECTIVES: To compare budesonide, a locally acting glucocorticoid with minimal systemic exposure, with conventional glucocorticoid treatment and placebo in rheumatoid arthritis. METHODS: A double blind, randomised, controlled trial over 12 weeks in 143 patients with active rheumatoid arthritis, comparing budesonide 3 mg daily, budesonide 9 mg daily, prednisolone 7.5 mg daily, and placebo. Particular attention was paid to the pattern of clinical response and to changes in the four week period following discontinuation of treatment. RESULTS: There were improvements in tender joint count and swollen joint count on budesonide 9 mg compared with placebo (28% for tender and 34% for swollen joint counts, p<0.05). Prednisolone 7.5 mg gave similar results, while budesonide 3 mg was less effective. ACR20 response criteria were met by 25% of patients on placebo, 22% on budesonide 3 mg, 42% on budesonide 9 mg, and 56% on prednisolone 7.5 mg. A rapid and significant reduction in symptoms and signs in response to budesonide 9 mg and prednisolone 7.5 mg was evident by two weeks and maximal at eight weeks. There was no evidence that budesonide provided a different pattern of symptom control from prednisolone, or that symptoms became worse than placebo treatment levels after discontinuation of glucocorticoid treatment. Adverse effects attributable to glucocorticoids were equally common in all groups. CONCLUSIONS: The symptomatic benefits of budesonide 9 mg and prednisolone 7.5 mg are achieved within a short time of initiating treatment, are maintained for three months, and are not associated with any rebound in symptoms after stopping treatment.

Adult↗

PubMed2004

Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed.

OBJECTIVE: To evaluate the efficacy and safety of monotherapy with adalimumab in patients with RA for whom previous DMARD treatment has failed. METHODS: In a 26 week, double blind, placebo controlled, phase III trial, 544 patients with RA were randomised to monotherapy with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, 40 mg weekly, or placebo. The primary efficacy end point was > or =20% improvement in the ACR core criteria (ACR20 response). Secondary efficacy end points included ACR50, ACR70, EULAR responses, and the Disability Index of the Health Assessment Questionnaire (HAQ DI). RESULTS: After 26 weeks, patients treated with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, and 40 mg weekly had significantly better response rates than those treated with placebo: ACR20 (35.8%, 39.3%, 46.0%, 53.4%, respectively v 19.1%; p< or =0.01); ACR50 (18.9%, 20.5%, 22.1%, 35.0% v 8.2%; p< or =0.05); ACR70 (8.5%, 9.8%, 12.4%, 18.4% v 1.8%; p< or =0.05). Moderate EULAR response rates were significantly greater with adalimumab than with placebo (41.5%, 48.2%, 55.8%, 63.1% v 26.4%; p< or =0.05). Patients treated with adalimumab achieved better improvements in mean HAQ DI than those receiving placebo (-0.29, -0.39, -0.38, -0.49 v -0.07; p< or =0.01). No significant differences were found between adalimumab and placebo treated patients for serious adverse events, serious infections, or malignancies. Injection site reaction occurred in 10.6% and 0.9% of adalimumab and placebo treated patients, respectively (p< or =0.05). CONCLUSION: Among patients with RA for whom previous DMARD treatment had failed, adalimumab monotherapy achieved significant, rapid, and sustained improvements in disease activity and improved physical function and was safe and well tolerated.

Adalimumab↗

PubMed2004

[Valdecoxib (Bextra)].

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.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2002

[Horton's disease and extra-temporal vessel locations: role of 18FDG PET scan. Report of 3 cases and review of the literature].

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.

Aged↗

PubMed2002

Cytokine production from sputum cells after allergenic challenge in IgE-mediated asthma.

BACKGROUND: Th2 cytokine production from airway cells is thought to govern the eosinophilic airways inflammation in allergic asthma. Induced sputum has become a widely used technique to assess airways inflammation. 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 challenge 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.

Adult↗

PubMed2002

A positive response to infliximab in Crohn disease: association with a higher systemic inflammation before treatment but not with -308 TNF gene polymorphism.

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-alpha 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 polymorphism were not significantly different between responders and non-responders--with the exception of a slightly higher TNF2 frequency in non-responders 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.

Adolescent↗

PubMed2001

The occurrence of the ilio-lumbar syndrome in a spinal cord injury patient.

STUDY DESIGN: Case report of a 71-year-old man having sustained a spinal cord injury (SCI) for 26 years. He started to suffer from low back pain 21 years after his onset and this was diagnosed as ilio-lumbar syndrome (ILS). OBJECTIVES: To describe the problem of low back pain occurring after a change of wheelchair in a SCI, and to indicate the importance of the ilio-lumbar syndrome as a possible cause of low back complaint. OUTCOME: Clinical findings supported by echotomography confirmed the diagnosis of ILS in our case. CONCLUSION: ILS should be considered when some changes and deterioration of the status of SCI occur due to low back complaint.

Aged↗

PubMed2001

Relationship between bone mass density and tensile strength of the skin in women.

BACKGROUND: Skin and bone may be affected similarly during the climacteric and during long-term corticotherapy. Little is known about the correlation between the respective alterations in bone mass density (BMD) and tensile strength of the skin. MATERIALS AND METHODS: A total of 100 women aged 19-88 years, receiving, or not, hormone replenishment therapy or systemic corticosteroids, were enrolled in the study. Tensile strength of the inner forearm skin was measured using the suction method operated in both the steep and progressive-force application modes. BMD was measured by dual X-ray absorptiometry at the hip, femoral neck and lumbar spine. RESULTS: Being heterogeneous, the population of volunteers yielded a wide range of BMD and cutaneous tensile strength values. However, significant correlations were found between BMD and tensile skin parameters. In particular, a positive correlation was yielded between the biological elasticity of skin and the BMD of the hip and femoral neck. CONCLUSION: An overall correlation is shown between skin elasticity on a relatively sun-protected area and cortico-trabecular BMD.

Absorptiometry, Photon↗

PubMed2001

Increased response of blood eosinophils to various chemotactic agents in quiescent Crohn disease.

BACKGROUND: The number of eosinophils is increased in the mucosae of the digestive and the respiratory tracts in Crohn disease, even clinically quiescent. The mechanisms underlying this panmucosal eosinophilia are unknown. METHODS: The response of blood eosinophils to various chemotactic agents was assessed in 15 patients with clinically quiescent Crohn disease. The results were compared with 15 healthy controls. After purification, eosinophils were placed in Boyden microchambers and the chemotactic effect of PAF (10(-7) M), RANTES (50 ng/ml), IL-5 (0-20 ng/ml), IL-8 (0-50 ng/ml), Eotaxin (0-50 ng/ml) was evaluated. The number of eosinophils in induced sputum of these Crohn disease patients and controls was also assessed and the correlation between chemotaxis and eosinophil count in induced sputum was studied. RESULTS: PAF and RANTES induced a chemotactic effect both in Crohn disease patients and controls. The chemotactic index was significantly higher in Crohn than controls for PAF (2.09+/-0.24 versus 1.37+/-0.14; P < 0.05) but not RANTES. With IL-5, IL-8 and Eotaxin, there was no detectable chemotactic effect in controls while in Crohn, we observed a significant dose-dependent chemotactic effect. Furthermore, with Eotaxin 50 ng/ml, the chemotactic index was significantly higher in Crohn disease patients than controls (2.42+/-0.18 versus 1.56+/-0.28; P < 0.05). A significant increase in sputum eosinophil count and a significant decrease in sputum macrophage count in Crohn disease were observed. However, there was no correlation between eosinophil chemotaxis and sputum eosinophil count in individual patients. CONCLUSION: There is an increased response of blood eosinophils to various chemotactic agents, mainly PAF and Eotaxin, in clinically quiescent Crohn disease. This may participate in the mucosal infiltration by eosinophils in this disease.

Adult↗

PubMed2001

WHO Collaborating Centre consensus meeting on anti-cytokine therapy in rheumatoid arthritis.

Severe adult rheumatoid arthritis is a cause of progressive disability and increased mortality across Europe. A cure for the disease remains elusive, but control of symptoms and maintenance of individual independence is possible. Anti-cytokine therapies offer a new approach to disease management. They are effective after the failure of full doses of methotrexate, and are at least as effective as methotrexate in retarding the progression of radiological changes. Until more is known about the long-term safety and efficacy of these drugs they should be reserved for patients with severe disease who are progressing despite adequate doses of methotrexate or other disease-modifying anti-rheumatic drugs. They should be continued until therapeutic failure or intolerance. A comprehensive health economic evaluation is needed to optimally direct the use of these drugs. This should be undertaken when long-term safety and efficacy studies are completed.

Antibodies, Monoclonal↗