Rheumatoid Arthritis: Appelboom T

Appelboom T, Gangji V, Margaux J, Steinfeld S. · No affiliation provided · Rev Med Brux. · Pubmed #12584936 No free full text.

Abstract: Actually, 18 rheumatologists and specialists in physical therapy are collaborating in the Department, allowing to develop possibilities for the diagnosis and therapeutic challenge of patients suffering from disorders of the locomotor system. Accordingly, the knowledge, the know-how, the experience plus the willingness to make a good job are used for helping the patient, for contributing to medical progress and also for the education of future medical doctors. Our department has significantly contributed to a better understanding and therapeutic approach of rheumatoid arthritis, Sjogren's syndrome, aseptic necrosis, osteoporosis, osteoarthritis, and inflammation; it has been among the first in the world to offer new therapeutic modalities, otherwise not accessible and, to help a series of hopeless patients. In addition, a new sector for a performing rehabilitation has been recently developed. Accordingly, during these mast twenty years, a performing department with a motivated team has been developed offering a maximum of medical services for the community and ready for the challenges of tomorrow.

Appelboom T. · Division of Rheumatology and Physical Medicine, Erasmus University Hospital, University of Brussels, Brussels, Belgium. · Bone. · Pubmed #12008165 No free full text.

Abstract: Salmon calcitonin (especially intranasal) provides an interesting analgesic effect in a series of painful conditions including reflex sympathetic dystrophy syndrome, adhesive capsulitis, ankylosing spondylitis, rheumatoid arthritis, vertebral crush fractures and metastasis, phantom limb pain, etc. In addition, in preliminary series, calcitonin shows an unexpected benefit to vasomotor changes and peptic ulcer. Yet the experience in these conditions is limited and needs confirmation. By comparison with the injectable, the intranasal route seems particularly interesting because of less undesirable effects, and a more rapid and probably more powerful analgesia.

Moreland LW, Alten R, Van den Bosch F, Appelboom T, Leon M, Emery P, Cohen S, Luggen M, Shergy W, Nuamah I, Becker JC. · Spain Rehabilitation Center, University of Alabama at Birmingham, 1717 6th Avenue South, Room 068, Birmingham, AL 35294-7201, USA. · Arthritis Rheum. · Pubmed #12115176 links to  free full text

Abstract: OBJECTIVE: T cells are involved in the pathogenesis of rheumatoid arthritis (RA). In animal models of autoimmune diseases, blockade of costimulatory molecules on antigen-presenting cells has been demonstrated to be effective in preventing or treating this disease by preventing T cell activation. To date, the effect of costimulatory blockade in patients with RA is unknown. The goal of this multicenter, multinational study was to determine the safety and preliminary efficacy of costimulatory blockade using CTLA-4Ig and LEA29Y in RA patients who have been treated unsuccessfully with at least 1 disease-modifying agent. METHODS: CTLA-4Ig, LEA29Y (0.5, 2, or 10 mg/kg), or placebo was administered intravenously to 214 patients with RA. Patients received 4 infusions of study medication, on days 1, 15, 29, and 57, and were evaluated on day 85. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (ACR20). All patients were monitored for treatment safety and tolerability. RESULTS: CTLA-4Ig and LEA29Y infusions were well tolerated at all dose levels. Peri-infusional adverse events were carefully monitored, and showed similar incidence across all dose groups with the exception of headaches, which were slightly more frequent in the 2 treatment groups. The incidence of discontinuations due to worsening of RA was 19%, 12%, and 9% at 0.5, 2, and 10 mg/kg, respectively, in the CTLA-4Ig-treated patients and 3%, 3%, and 6% at 0.5, 2, and 10 mg/kg, respectively, in the LEA29Y-treated patients (versus 31% in the placebo group). ACR20 responses on day 85 had increased in a dose-dependent manner (23%, 44%, and 53% of CTLA-4Ig-treated patients and 34%, 45%, and 61% of LEA29Y-treated patients at 0.5, 2.0, and 10 mg/kg, respectively, versus 31% of placebo-treated patients). CONCLUSION: Both of the costimulatory blocking molecules studied were generally safe and well tolerated. As compared with placebo, both CTLA-4Ig and LEA29Y demonstrated efficacy in the treatment of RA.

Steinfeld SD, Demols P, Salmon I, Kiss R, Appelboom T. · Department of Rheumatology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. · Arthritis Rheum. · Pubmed #11665979 No free full text.

Abstract: OBJECTIVE: Tumor necrosis factor alpha (TNFalpha) is a proinflammatory cytokine involved in the pathogenesis of Sjögren's syndrome (SS), and blockade of TNFalpha may reduce the activity of the disease. The purpose of this study was to evaluate the safety and potential efficacy of infliximab, a chimeric human-mouse anti-TNFalpha monoclonal antibody, in patients with active primary SS. METHODS: This was a single-center, open-label pilot study. Sixteen patients with active primary SS received 3 infusions of infliximab (3 mg/kg) at 0, 2, and 6 weeks. Standard clinical assessment, complete ophthalmologic testing, and functional evaluation of salivary flow were performed at baseline and at weeks 2, 6, 10, and 14. RESULTS: All patients completed the study. There was statistically significant improvement in all clinical and functional parameters, including global assessments (patient's global assessment, patient's assessment of pain and fatigue, physician's global assessment), erythrocyte sedimentation rate, salivary flow rate, the Schirmer I test, tender joint count, fatigue score, and dry eyes and dry mouth. This clinical benefit was observed at week 2 and was maintained throughout the study and the 2-month followup period. The treatment was well tolerated in all patients, and no significant adverse events were seen. No lupus-like syndrome was observed, and no anti-double-stranded DNA antibodies were observed that were attributable to infliximab therapy. CONCLUSION: In patients with active primary SS, a loading-dose regimen of 3 infusions of infliximab provided a fast and significant clinical benefit without major adverse reactions. It was possible to maintain statistically significant improvement for up to 8 weeks after the third infusion.

Steinfeld SD, Demols P, Van Vooren JP, Cogan E, Appelboom T. · Division of Rheumatology, Erasmus Academic Hospital, Université Libre de Bruxelles, Brussels, Belgium. · Rheumatology (Oxford). · Pubmed #10515640 links to  free full text

Abstract: OBJECTIVE: To evaluate the efficacy of the administration of zidovudine (AZT), an antiretroviral drug, in patients with primary Sjögren's syndrome (SS). METHODS: Seven female patients (age 57 +/- 8.6 yr) with primary SS were enrolled in an open, uncontrolled trial of AZT (250 mg b.i.d.) for the treatment of primary SS. The efficacy variables were oral and ocular dryness symptoms, fatigue, tender points, physician's and patient's global assessments (GA), ocular function tests (fluorescein tear break-up time, Schirmer's test, Rose Bengal staining) and laboratory parameters [erythrocyte sedimentation rate (ESR), serum IgG, IgA and IgM]. RESULTS: A significant improvement was observed in all subjective manifestations, as well as the objective parameters of ocular dryness. The treatment was well tolerated, except for mild and transitory gastrointestinal disturbances in 6/7 patients. Laboratory parameters did not change significantly. The clinical benefit persisted in 5/7 patients 1 month after the end of therapy. CONCLUSION: AZT seems to be effective and well tolerated in patients with primary SS.

Terrones-Munoz V, Mélot C, Gangji V, Steinfeld S, Appelboom T. · Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. · Eur J Pediatr. · Pubmed #16602001 No free full text.

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Appelboom T. · Erasmus Hospital, University of Brussels, Belgium. · Rheumatology (Oxford). · Pubmed #15840609 links to  free full text

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Appelboom T, Emery P, Tant L, Dumarey N, Schoutens A. · Division of Rheumatology, Erasmus University Hospital, Brussels, Belgium. · Rheumatology (Oxford). · Pubmed #12777638 links to  free full text

Abstract: OBJECTIVE: To study the frequency of technetium-99m-positive ciprofloxacin scans (Infecton scintigraphy) thought to be specific for bacterial DNA in patients with arthritis and to assess the clinical relevance of positive scans. METHODS: Four groups of adults with arthritis were studied. Group 1: 53 patients with inflammatory arthritis, 36 with spondylarthropathy (SpA) and 17 with rheumatoid arthritis (RA); group 2: five patients with crystal arthropathy; group 3: those patients with osteoarthritis (OA) of the knee, wrist or spine; and group 4: 28 patients who had no arthritis but were being investigated for renal infection. Patients were injected with 10 mCi 99Tcm-ciprofloxacin with isotope uptake analysis at 4 h. Clinically swollen joints were assessed by a rheumatologist and the positive scans assessed by a physician in nuclear medicine. RESULTS: Increased Infecton uptake was noted in inflamed joints independent of the pathology. It was seen in 10 of 17 patients with SpA, 12 of 17 with RA, all five with crystal arthropathy, eight with knee OA, two with wrist OA, none with spinal OA and none in uninflamed joints. A close correlation between clinically swollen joints and articular Infecton uptake was noted (P = 0.0003), with the uptake being in the distribution of the synovial perimeter. Additional uptake was noted in the abdomen (n = 9) and pulmonary region (n = 2) of SpA patients. CONCLUSION: The Infecton scan is not specific for infection but may be a reliable procedure for identifying the presence and distribution of the inflammation within joints. It has the potential for monitoring the response of inflamed joints to treatment.

Steinfeld SD, Demols P, Appelboom T. · Department of Rheumatology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. · Arthritis Rheum. · Pubmed #12483735 links to  free full text

Abstract: OBJECTIVE: To evaluate the safety and efficacy of a maintenance regimen of infliximab in patients with active primary Sjögren's syndrome (SS) over a 1-year period. METHODS: This followup study included 10 of the 16 patients with primary SS who participated in a pilot study. Patients who continued to have symptoms received additional infusions of infliximab for 1 year. RESULTS: All patients completed the 1-year followup for evaluation of efficacy. After 1 year, a statistically significant decrease in global and local disease manifestations was observed in all 10 patients. Treatment was generally well tolerated, with the main side effect being a mild, self-limited infusion reaction. CONCLUSION: Sustained improvement of active primary SS may be possible with infliximab treatment.

Steinfeld SD, Appelboom T, Delporte C. · Erasme University Hospital Christine Delporte, Brussels, Belgium. · Arthritis Rheum. · Pubmed #12209534 links to  free full text

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Appelboom T. · Erasmus University Hospital, University of Brussels, 808 route de Lennik, B-1070 Brussels, Belgium. · Rheumatology (Oxford). · Pubmed #12173278 links to  free full text

Abstract: Preserved human remains, artefacts and works of art contain records of the existence and prevalence of arthropathies, even in the absence of medical texts or formal written accounts, although these also exist for some epochs and cultures. Example objects from the Museum of Medical History in Brussels have been used to illustrate the magnitude of the burden of pain throughout the ages and how rheumatic diseases have indiscriminately afflicted people regardless of their positions in life or occupations. These include both osteoarthritis (OA) and rheumatoid arthritis (RA), as well as the seemingly ubiquitous gout and various skeletal deformities. Adequate pain management has been severely hampered, historically, by obstacles to a comprehensive and systematic classification of diseases posed by the social, religious and philosophical mores of the time, which made differential diagnosis almost impossible to achieve. However, despite this shortcoming, serendipitous events meant that precursors of modern medicines, such as willow bark extracts, were in routine use from the earliest recorded times. It has taken several millennia, however, before empirical treatment has given way to pharmacological rationale. The first clinically acceptable synthetic derivative of the active principle in willow, aspirin, became available only at the turn of the nineteenth century, while non-steroidal anti-inflammatory drugs (NSAIDs) did not arrive on the market until some 60 yr later. At the cusp of the twentieth and twenty-first centuries, physicians have a wider choice of analgesics available than ever before, including the cyclooxygenase-2 inhibitors, which represent the first major advance in NSAID development since the synthesis of the latter compounds themselves.

Emery P, Reginster JY, Appelboom T, Breedveld FC, Edelmann E, Kekow J, Malaise M, Mola EM, Montecucco C, Sanda M, Sany J, Scott DL, Serni U, Seydoux G. · University of Leeds, Rheumatology and Rehabilitation Research Unit, 36 Clarendon Road, Leeds LS2 9NZ, UK. · Rheumatology (Oxford). · Pubmed #11426031 links to  free full text

Abstract: 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.

Steinfeld S, Maho A, Chaboteaux C, Daelemans P, Pochet R, Appelboom T, Kiss R. · Divisions of Rheumatology, Erasme University Hospital, Brussels, Belgium. · Lab Invest. · Pubmed #11092531 No free full text.

Abstract: Various proteases are expressed in the minor salivary glands (MSG) of patients with Sjögren's syndrome (SS), and as we have already shown, prolactin is neosynthesized in the acinar cells of patients with SS. The present study aims to characterize the influence of PRL on the expression of cathepsin B and D in the MSG of patients with SS. Cathepsin B and D expression was investigated immunohistochemically in MSG of 30 patients with SS and 15 healthy volunteers. The presence of cathepsin B and D mRNAs was checked in three SS patients and three control subjects by means of reverse transcription-polymerase chain reaction (RT-PCR). The specificity of the anti-cathepsin B and D antibodies used for the immunohistochemistry was checked by means of western blotting analysis. The influence of prolactin on the immunohistochemical expression of cathepsin B and D was quantitatively assayed by computer-assisted microscopy at three different doses (5, 50, and 500 ng/ml) on eight MSGs (four control subjects and four patients with SS) maintained ex vivo under organotypic cultures. This influence was also investigated at the mRNA level. Whereas cathepsin B immunopositivity was absent from glandular epithelial cells of healthy subjects and only slightly present in SS patients, cathepsin D immunoreactivity was considerably greater (p < 0.0001) in both the acini and the ducts of patients with SS as compared with control subjects. Cathepsin B, but not D, was also expressed in about 20% of infiltrating mononuclear cells of SS patients. Treatment of both healthy and SS minor salivary glands with PRL significantly (p < 0.05 top < 0.0001) enhanced cathepsin B and D expression in acinar and ductal cells at both protein and mRNA levels. PRL produced locally in MSGs of SS patients, but not those of healthy subjects, could play a role in the pathogenesis of Sjogren's syndrome, if only through the activation of proteolytic activity on the part of cathepsins B and D.

Steinfeld S, Penaloza A, Decaestecker C, Rommes S, André S, Schüring MP, Danguy A, Appelboom T, Kiss R, Gabius HJ. · Department of Rheumatology, Erasmus Academic Hospital, Brussels, Belgium. · J Rheumatol. · Pubmed #10955332 No free full text.

Abstract: OBJECTIVE: The profile of glycans and their recognition by endogenous receptors (lectins) are increasingly attributed to disease process. Monitoring this can provide information on the pathogenesis of Sjögren's syndrome (SS). Commonly, plant lectins are employed for phenomenological glycan mapping. To go beyond this approach restricted to binding of exogenous probes, new markers measure ligand properties of glycans to human (not plant) lectins and the presence of sugar receptors completing a protein-carbohydrate recognition system. Carrier-immobilized sugar epitopes (neoglycoproteins) and purified human lectins establish this innovative panel. METHODS: The host defence molecules mannan binding lectin, serum amyloid P component, and the macrophage migration inhibitory factor-binding sarcolectin, selected for their involvement in cell destructive mechanisms, were purified and labeled. The plant lectins SNA and MAA were employed to monitor regulation of potential ligand sites for I-type lectins and galectins. Asialofetuin was tested as a "pan-galectin selective" probe. The specific binding characteristics were determined by quantitative morphometry and statistical analysis. RESULTS: Diagnostic information emerged from this analysis. The percentage of stained tissue area was significantly different between SS and control specimens after processing with GlcNAc and Man-bearing neoglycoproteins and the 2 tested serum lectins. For separation of cases of primary and secondary SS, the staining intensity with the asialoglycoprotein, sarcolectin, and the exogenous alpha2,6-sialylated glycan-binding lectin SNA was statistically significant. CONCLUSION: Saccharide-presenting probes to measure the cellular capacity to bind glycan epitopes and human lectins as sensors for endogenous binding sites have proven to be useful as diagnostic tools. We suggest the differences we observed reflect aberrations from the normal cellular homeostasis with relevance for the pathogenesis of SS and its manifestation as a primary or secondary syndrome.

Steinfeld S, Rommes S, François C, Decaestecker C, Maho A, Appelboom T, Heizmann CW, Kiss R, Pochet R. · Division of Rheumatology, Erasme University Hospital, Brussels, Belgium. · Lab Invest. · Pubmed #10701693 No free full text.

Abstract: Characterization of endogenous synthesis of prolactin (PRL) proteins and their cellular localization in labial salivary glands of patients with Sjogren's syndrome (SS) were achieved. PRL, PRL-receptors (PRL-R), and S100A6 protein were detected by immunohistochemistry. In situ prolactin synthesis was investigated in controls and SS patients by ex vivo incubation of minor salivary glands biopsies and immunoprecipitation assay. Increased PRL-immunoreactivity was found in cytoplasmic acinar epithelial cells in SS patients compared with normal subjects. PRL-R was distributed only in ductal epithelial cells in which S100A6 protein (a PRL-R-associated protein) was also present. PRL, PRL-R, or S100A6-immunoreactivity was not detected in infiltrating mononuclear cells. Immunoprecipitation demonstrated that PRL synthesis occurred in minor salivary glands with increased synthesis of two distinct PRL-like proteins (one major band at 60 kDa and a minor at 16 kDa) in SS glands compared with normal glands. Expression of PRL gene was demonstrated in SS salivary glands using RT-PCR. A positive correlation was found between the presence of PRL-like proteins in acinar epithelial cells of SS patients and clinical extraglandular manifestations. The presence of anti-Ro and anti-La antibodies also positively correlated with a higher percentage of PRL in acinar epithelial cells. In conclusion, PRL-like proteins are synthetized and overexpressed in glandular epithelial cells of labial salivary glands from SS patients and correlate with the aggressiveness of the disease.

Penaloza A, Decaestecker C, Ribaï P, Nagy N, Salmon I, Appelboom T, Danguy A, Kiss R, Steinfeld S. · Laboratory of Histology, Faculty of Medicine, Université Libre de Bruxelles, Belgium. · Clin Exp Rheumatol. · Pubmed #10609070 No free full text.

Abstract: OBJECTIVE: To investigate the composition and expression of sialic acid in the labial salivary glands (LSG) in Sjögren's syndrome (SS). METHODS: LSG of 19 patients with primary SS (n = 11) or secondary SS (n = 8) were studied. Specimens from 7 healthy women served as controls. Computer-assisted microscopy was employed to quantitatively determine the percentage of positive structures, the staining intensity and the heterogeneity for the 4 biotinylated plant lectins Tritricum vulgaris L. (WGA), Maackia amurensis (MAA), Sambucus nigra (SNA) and Canavalia ensiformis L. (Con A). RESULTS: In the acini there was a significant decrease in the staining heterogeneity of WGA in SS compared to controls; the same was observed with respect to MAA staining in the connective tissue and extralobular ducts. In the intralobular ducts, primary SS differed from normal and secondary SS mainly in terms of a decrease in the percentage of positively labeled MAA tissue. In addition, Con A stained acinar cells were significantly more numerous in secondary SS compared with primary SS. CONCLUSION: Differences in the degree of glycoconjugate sialylation were found in SS labial salivary glands, and may play a role in the disease process.

Durez P, Appelboom T, Pira C, Stordeur P, Vray B, Goldman M. · Hôpital Erasme, Department of Rheumatology, Université Libre de Bruxelles, Brussels, Belgium. · Int J Immunopharmacol. · Pubmed #10501627 No free full text.

Abstract: Mycophenolate mofetil (MMF) is a new immunosuppressive agent currently used in organ transplantation and under evaluation in immune-mediated inflammatory disorders such as rheumatoid arthritis. Although MMF was shown to inhibit purine nucleotide synthesis in lymphocytes, it is still unclear whether it might also exert direct antiinflammatory actions in vivo. To address this question, we evaluated the effects of MMF administration on the responses of mice to a single challenge with bacterial lipopolysaccharide (LPS). We observed that MMF treatment inhibits the release of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) upon LPS injection whereas it promotes IL-10 production. In parallel, MMF was found to protect mice from LPS-induced lethality. Inhibition of TNF-alpha release was also observed in IL-10-deficient mice indicating that it does not exclusively depend on the upregulation of IL-10 endogenous synthesis. In view of the differential effects of MMF on the LPS-induced production of TNF-alpha and NO on one hand and that of IL-10 on the other hand, we conclude that beside its immunosuppressive action at the lymphocyte level, MMF is also endowed with antiinflammatory properties.

Steinfeld S, Noel JC, Appelboom T. · Erasmus University Hospital, Brussels, Belgium. · Arthritis Rheum. · Pubmed #10323467 links to  free full text

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Steinfeld S, Penaloza A, Ribaï P, Decaestecker C, Danguy A, Gabius HJ, Salmon I, Appelboom T, Kiss R. · Department of Rheumatology, Erasmus Academic Hospital, Brussels, Belgium. · J Rheumatol. · Pubmed #10229404 No free full text.

Abstract: OBJECTIVE: Sjögren's syndrome (SS) is an autoimmune exocrinopathy. The mannose binding lectin (MBL), a pluripotent molecule of the innate immune system, is involved in the pathogenesis of autoimmune diseases. We investigated whether specific ligands for MBL and MBL related structures could be reliable markers in cases of SS. METHODS: The labial salivary glands of 19 patients fulfilling the diagnostic criteria for primary (n=11) and secondary SS (n=8) were studied. Seven healthy women served as controls. Computer assisted microscopy was employed to determine quantitatively the percentage of positive structures (acini, ducts, and interlobular connective tissue), the staining intensity, and the level of staining heterogeneity for 4 glycohistochemical probes including wheat germ agglutinin and concanavalin (Con A) as lectins, and mannose and N-acetylglucosamine as parts of neoglycoproteins. The data were evaluated by discriminant analysis. RESULTS: The data strongly suggest that MBL related structures, if not MBL itself, could play distinct roles in the pathogenesis of primary versus secondary SS. Further, quantitative determination of the level of expression of D-mannose and N-acetylglucosamine and their respective binding sites in labial salivary gland acini offers a powerful diagnostic tool for distinguishing primary from secondary SS. CONCLUSION: In SS labial salivary glands, determination of the level of acceptor sites for wheat germ agglutinin, Con A, D-mannose, and N-acetylglucosamine provides information on the roles played by glycoforms in SS. The methodology and data described in this paper should provide pathologists with objective diagnostic markers for SS. Our results should enhance the biological understanding of this pathology.

Hatem S, Hoyaux D, De Decker V, Appelboom T, Pochet R, Steinfeld S. · No affiliation provided · Clin Exp Rheumatol. · Pubmed #12175122 No free full text.

This publication has no abstract.