Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
9884523 [Cataract in uveitis in children]. 1998 PURPOSE: To evaluate the anatomical and functional state of eyeballs after cataract extraction in uveitis in children and to analyze the factors affecting visual outcome. MATERIAL AND METHODS: Among 182 examined eyes with uveitis we have observed cataract in 22 eyeballs of 17 children (12%). Before operation in 72.7% cases visual acuity was less or equal 0.02, in the others it was not more than 0.2. The age of patients ranged between 2 and 18 years, the mean age 8 years. The cause of uveitis was: chronic tonsillitis or sinusitis in 6 patients, juvenile rheumatoid arthritis in 2 patients, heterochromic Fuchs iridocyclitis in 2 children, in the others the cause was unknown. In 4 eyeballs (18%) we have observed increased intraocular pressure before operation. Follow-up ranged from 6 months to 15 years, the mean was 5 years. RESULTS: We have obtained normal visual acuity in 31.8% cases and better than 0.1 in 68.2% od eyes. In children with juvenile rheumatoid arthritis, 2 eyeballs lost light perception as a result of corpus vitreous fibrosis and in one case we have observed only light perception. Optic nerve glaucomatous neuropathy was the cause of poor functional result in 2 eyes (0.02 and 0.04). Another causes of not satisfactory visual acuity were: corneal dystrophy (2 eyes), cystoid macular oedema (2 eyes) and amblyopia ex anopsia (2 eyes). CONCLUSIONS: We have obtained normal or good visual acuity in majority of the operated eyes. The causes of poor vision were the anatomical changes after uveitis before the cataract extraction.
9686682 Antisense targeting of the urokinase receptor blocks urokinase-dependent proliferation, ch 1998 Jul Proliferation and invasion of synovial pannus in rheumatoid arthritis and cartilage remodeling in osteoarthritis are key events in development of disability of arthritic joints. The mechanisms that trigger these events are still poorly understood. The production of urokinase-type plasminogen activator (u-PA) by synovial cells and chondrocytes and the subsequent interaction of u-PA with its membrane receptor (u-PAR) is under the control of a variety of growth factors and cytokines released within the inflamed joints. Here we show that u-PA, on interaction with the specific receptor, regulates movement and invasion as well as proliferation of human synovial cells and chondrocytes. Targeting the urokinase receptor with an antisense oligonucleotide blocks the u-PA-dependent synoviocyte and chondrocyte proliferation and chemoinvasion, suggesting a possible use for this new class of drugs in the progression of the disease in rheumatoid arthritis and osteoarthritis.
11415720 Foot pressure distribution: methodology and clinical application for children with ankle r 1997 Apr INTRODUCTION:: Foot pressure measurements furnish information about distribution of pressures, forces, time and contact areas under the foot during standing and walking. Foot pressure measurement has been used in a number of rehabilitation and athletic applications in adults, however, little has been published regarding the clinical usefulness of this technology for children with disabilities. Children with juvenile rheumatoid arthritis (JRA) are reported to have various foot deformities and gait deviations and clinicians report that the children may have foot pain such as metatarsalgia. These may be treated with specially fitted shoes, shoe modifications or ankle foot orthoses. The purpose of this preliminary study was to describe the methodology used to quantify foot pressure distribution patterns and, further, to describe the patterns seen in individual children with JRA compared to aged matched typical children without JRA. METHODS:: Pressure, area and force were measured using the EMED-F system including a platform with 2048 capacitive pressure sensors and a computerized data collection and analysis system. Children were asked to walk comfortably and normally across the platform while time, pressure and area measurements were automatically taken. Other data collected were height and weight, observational gait analysis and lower extremity range of motion measurements. Data are reported for the entire foot, as well as particular areas of the foot that are of interest. For this study, eight discrete areas or masks were identified (medial and lateral heel, medial and lateral midfoot, first metatarsal, lateral four metatarsals, great toes and four lateral toes) for description. Information reported for each area and the total foot included force, peak pressure, total area, pressure time integral and force time integral. Data from three pairs of children were analysed and differences were described. RESULTS:: Several differences in the descriptive data were noted and will be highlighted. Children with JRA had striking asymmetries in several variables, higher peak pressures and in increased total foot pressure time integrals and force time integrals. This information is presented to improve our understanding of the patterns under the foot so that (1) appropriate treatment strategies for foot impairments may be better prescribed for children with JRA and (2) to assist in planning for treatment of gait abnormalities. This preliminary work will also form the basis for determining the clinically meaningful variables to consider in a larger study and statistical analysis.
9091902 Lack of evidence of systemic inflammatory rheumatic disorders in symptomatic women with br 1997 Apr Breast implants containing silicone have been used for approximately 30 years for breast augmentation or reconstruction. In general, the implants have been well tolerated and reports have indicated a high degree of patient satisfaction. Nonetheless, there have been anecdotal reports of patients with musculoskeletal complaints that have been attributed to silicone breast implants. To investigate this further, we prospectively examined 70 women with silicone breast implants who had complaints that they or their referring physicians thought were related to their implants. On clinical examination, the majority of the patients had fibromyalgia, osteoarthritis, or soft-tissue rheumatism. One patient had rheumatoid arthritis, which predated her implants, and one had Sjõgren's syndrome. Because many of our patients had myalgic symptoms, we further evaluated these patients by measuring circulating levels of soluble factors including interleukin-6, interleukin-8, tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1, and soluble interleukin-2 receptor, which have been previously found to be elevated in patients with inflammatory diseases. We found that the levels of these molecules in women with silicone breast implants were not different from those seen in normal subjects and were significantly less than those seen when examining chronic inflammatory disorders such as rheumatoid arthritis or systemic lupus erythematosus. In summary, our clinical and laboratory evaluation of symptomatic breast implant patients argues against an association of silicone breast implants with a distinctive rheumatic disease or a systemic inflammatory disorder. Given these findings and the clinical picture, it is our impression that most symptomatic women with silicone breast implants have well-delineated noninflammatory musculoskeletal syndromes. Moreover, these data fail to support the concept that their symptoms are due to a systemic inflammatory response related to their implants.
11602484 Papulopustular skin lesions are seen more frequently in patients with Behçet's syndrome w 2001 Nov OBJECTIVE: To determine the prevalence of acneiform skin lesions (comedones, papules, and pustules) in patients with Behçet's syndrome (BS) with arthritis. METHODS: Study groups included 44 patients with BS with arthritis (32 men, 12 women, mean (SD) age 37.8 (8.9)), 42 patients with BS without arthritis (31 men, 11 women, mean age 35.5 (6.4)), 21 patients with active rheumatoid arthritis (five men, 16 women, mean age 48.8 (14)), and 33 healthy volunteers (28 men, five women, mean age 40.1 (8.1)). All probands and controls were examined by a rheumatologist and a dermatologist, in a prospective and masked protocol. An ophthalmological evaluation was performed if necessary. Skin lesions, including comedones, papules, and pustules, were counted and scored as 0: absent, 1: 1-5, 2: 6-10, 3: 11-15, 4: 16-20, and 5: >20. RESULTS: Although there was no significant difference between the four groups in the prevalence of comedones, the number of papules and pustules was significantly higher in patients with BS with arthritis (p=0.0037 for papules and p<0.0001 for pustules) than in the remaining three groups. CONCLUSION: Acneiform skin lesions (papules and pustules) seem to be more frequent in patients with BS with arthritis. This suggest that the arthritis seen in BS may possibly be related to acne associated arthritis.
10403283 Inhibitory effect of annexin I on synovial inflammation in rat adjuvant arthritis. 1999 Jul OBJECTIVE: Annexin I is an endogenous antiinflammatory mediator, expressed in rheumatoid arthritis (RA) synovium, the contribution of which to autoregulation of the synovial inflammatory response has not been examined in models of RA. We investigated the antiinflammatory role of annexin I in rat adjuvant arthritis. METHODS: Rats with adjuvant-induced arthritis (AIA) were treated with a specific anti-annexin I monoclonal antibody (mAb), isotype control IgG, and/or dexamethasone. Clinical outcomes and synovial synthesis of tumor necrosis factor alpha (TNFalpha), prostaglandin E2 (PGE2), and nitric oxide were examined, and annexin I expression was assessed by flow cytometry and reverse transcription-polymerase chain reaction. RESULTS: Anti-annexin I mAb reversed the effects of dexamethasone on the clinical features of AIA and exacerbated AIA in the absence of exogenous glucocorticoid. Clinical exacerbation of AIA by anti-annexin I mAb was accompanied by significantly increased synovial TNFalpha and PGE2, suggesting that annexin I tonically inhibits the production of these mediators. Anti-annexin I mAb treatment was associated with significantly reduced leukocyte intracellular annexin I, despite increased annexin I messenger RNA expression, consistent with a depletion effect of extracellular mAb via the cell surface. CONCLUSION: Annexin I is a key endogenous inhibitory mediator of arthritis via mechanisms that include inhibition of cytokine and effector molecule production. Moreover, a synthesis-independent depletion of intracellular annexin I by extracellular antibody supports the hypothesis that externalization of annexin I is involved in its mode of action.
9182885 Amelioration of collagen II-induced arthritis in rats by the type IV phosphodiesterase inh 1997 Jun The effect of Rolipram, a selective inhibitor of the cyclic AMP specific phosphodiesterase (PDE IV) was evaluated in the rat collagen type II (RCII)-induced arthritis model in the DA rat. Rolipram was given either shortly before expected onset of disease (days 10-14) or shortly after the onset of clinically evident arthritis (days 15-19 after immunization). Administration at days 10-14 delayed the onset of arthritis for approximately 5 days, but the severity of arthritis was thereafter comparable to that seen in a non-treated control group. Rolipram treatment of animals with manifest arthritis inhibited further arthritis development and also tended to diminish its severity at a phase of disease where non-treated control animals showed a rapidly progressing disease development. Serum levels of antibodies to RCII were in all experiments similar between Rolipram-treated and control animals. An in situ hybridization method for determining cytokine mRNA synthesis in regional lymph nodes, after administration of Rolipram (at days 2-7), demonstrated a strong inhibitory effect on tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) mRNA expression, whereas no effects were seen on IL-2 mRNA synthesis after in vivo challenge with native RCII emulsified in Freund's incomplete adjuvant. The results thus demonstrate strong preventive as well as therapeutic effects of Rolipram in a model for arthritis that is very similar to human rheumatoid arthritis with respect to cytokine regulation, and suggest that Rolipram has its major effects in the effector stage of the arthritogenic immune response.
9353150 Anti-CD2 (OX34) MoAb treatment of adjuvant arthritic rats: attenuation of established arth 1997 Oct Anti-CD2 MoAbs have previously been shown to induce tolerance and to block B cell differentiation, T cell and monocyte activation. Since these immune functions are important in joint inflammation, we asked whether administration of the anti-CD2 MoAb OX34 has a beneficial effect on established rat adjuvant arthritis, a model of human rheumatoid arthritis, and how it affects CD2-bearing leucocyte subsets. Female Lewis rats with established adjuvant arthritis received a total of 5 mg OX34 or isotype-matched control MoAb starting on day 15 after adjuvant injection. Weight and arthritis score (AS) were measured in a blinded fashion. Peripheral blood cells were analysed for numbers of leucocyte subsets at various time points. Animals were killed on day 30 and lymphatic organs were processed for immunohistology. Clinically, OX34 treatment led to increased body weight and reduced AS. Although OX34 binds to CD4+ and CD8+ T cells in a comparable fashion, OX34 treatment reduced CD4+ T cells, but not CD8+ T cells. Among CD4+ T cells CD45RC+ ('naive') T cells virtually disappeared; CD45RC- ('recently activated') T cells were slightly reduced. A reduction of CD4+ T cells was also found in the lung, liver, bone marrow, spleen and lymph nodes. Down-modulation of the CD2 molecule by OX34, again, affected CD4+ T cells, suggesting a specific signal for CD4+ but not CD8+ T cells. In conclusion, the anti-CD2 MoAb OX34 attenuates established rat adjuvant arthritis. In spite of similar binding to CD4+ and CD8+ T cells, OX34 depletes only CD4+ T cells and down-modulates the CD2 molecule on these cells. These results suggest a therapeutic benefit from CD2-directed therapy for chronic types of arthritis.
10607494 Macromolecular transport across the superficial layer of articular cartilage. 2000 Jan OBJECTIVE: To study the role of the superficial layer of articular cartilage in the transport of macromolecular solutes. DESIGN: The articular cartilage of intact bovine carpal bones was incubated with(125)I-labeled bovine serum albumin, human IgG, or horse ferritin for 4 hours. Quadruplicate samples were first incubated with polymorphonuclear neutrophil elastase for 30 minutes to remove the outermost layer covering the articular surface. The rates of exchange of each macromolecule from excised tissue explants in the absence of a concentration gradient were measured at six different time points. The results were expressed as the fraction of radioactive protein exiting the cartilage per mm(2)of tissue, or as picomoles of labeled solute per mm(2). RESULTS: Exchange rates correlated well with molecular mass, and no apparent differences were detected between intact and elastase-treated tissues. However, when the results were expressed in terms of the total number of molecules within the tissue, it was apparent that IgG molecules accumulated in the intact cartilage in larger than expected numbers. This finding was not observed in experiments using elastase-treated tissue. CONCLUSION: These observations suggest that the outermost surface layer does not constitute a barrier to the transport of macromolecules into the deeper zones of the tissue. The higher IgG accumulation observed in intact cartilage suggests that the acidic outer layer of cartilage exhibited attractive interactions, probably ionic in nature, with the cationic fraction of IgG. These observations may relate to our previous work demonstrating that the sequestered immune complexes in the superficial zone of articular cartilage in rheumatoid arthritis, and in the antigen-induced arthritis model, are formed because pre-existing antibody normally present in cartilage irreversibly traps antigen within the tissue.
9767454 An anti-inflammatory role for interleukin-11 in established murine collagen-induced arthri 1998 Sep Interleukin-11 (IL-11) is a cytokine belonging to the IL-6 family which has both pro- and anti-inflammatory potential. Like IL-6 it can diminish tumour necrosis factor-alpha and IL-1 production, and augment immunoglobulin synthesis. We have explored the immunomodulatory effects of IL-11 treatment in mice in a model of inflammatory autoimmune joint disease, collagen-induced arthritis (CIA). Recombinant human IL-11 was administered at various doses to DBA/1 mice after the onset of CIA. IL-11 treatment caused a significant reduction in the clinical severity of established CIA, which was associated with protection from joint damage, as assessed by histology. Although there was a suggestion at high doses of IL-11 that the anticollagen type II (CII) response may have been augmented, there was no statistically significant effect of IL-11 treatment on anti-CII antibody levels. Similarly, the acute-phase reactant serum amyloid P was only elevated in mice receiving very high doses (50-100 microgram/day) of IL-11. Endogenous IL-11 was abundantly produced in synovial membrane cultures derived from CII-immunized mice with active disease, suggesting that, as in rheumatoid arthritis, this cytokine is spontaneously produced in the inflammatory response in CIA. The results presented here demonstrate an anti-arthritic immunoregulatory role for IL-11 in murine CIA, and suggest that IL-11 is a candidate therapeutic molecule for human inflammatory arthritic diseases.
9067522 Cytokine production in synovial tissue of mice with collagen-induced arthritis (CIA). 1997 Mar The kinetics of cytokine production in arthritic limbs of mice with CIA was determined by using modified immunohistochemical techniques. Tissue cryostat sections of undecalcified whole paws were analysed for the presence of tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-2, IL-4, IL-5 interferon-gamma (IFN-gamma), transforming growth factor-beta 2 (TGF-beta2) and TGF-beta3. Locally produced TNF-alpha, IL-6 and TGF-beta2 were observed within the lining layer, sublining and pannus at all stages of disease. The staining of TNF-alpha was particularly intense at the cartilage-pannus junction. In contrast to the monokines, IFN-gamma and TGF-beta3 were only expressed in scattered cells within the deeper layers of the synovia. Interestingly, IFN-gamma was not present in the late phase of CIA, despite the continued presence of TNF-alpha and IL-6 in the pannus. Production of IL-2, IL-4 or IL-5 was not detected in any joint. The observed pattern of a relative paucity of T cell-derived cytokines and an abundance of monokines during the late phase of T cell-dependent CIA indicates that the synovial cytokine pattern previously described in rheumatoid arthritis (RA) is fully compatible with a pathogenic role of T cells. The temporal as well as spatial dissociation between expression of T cell-derived cytokines and monokines indicates that T cell-independent mechanisms may also be of importance in the triggering of monokine production during arthritis.
11583059 The treatment of juvenile arthritis. 2001 Jul Until recently, two different classification systems for juvenile arthritis (JA) were utilised, each with its own terminology and subclassification. It has been recognised that particularly within the polyarticular and pauciarticular groups, many distinct subsets exist each with a different prognosis. As a result, a new classification system for JA has been developed. It is hoped that this will allow more accurate assessment of incidence and aetiology of the various subtypes in future generations and in time will allow therapy to be targeted at those most likely to achieve benefit. Since there is a new classification system for JA, the vast majority of published clinical studies were performed using the old classification system. For the purposes of this review, unless otherwise stated, the American College of Rheumatology classification will be used. This is outlined in Table 1 with clinical features of the major subtypes described in Table 3. This review will cover current best practice and discuss future directions for research using the recent advances in the treatment of rheumatoid arthritis (RA) as a model.
11036835 Treatment of established collagen induced arthritis with prostaglandin E1 incorporated in 2000 Oct OBJECTIVE: In view of evidence obtained from in vitro and in vivo experiments that prostaglandin E1 (PGE1) has regulatory effects on disordered immune responses and inflammation, we investigated whether lipo-PGE1, an efficient drug delivery system incorporating PGE1 into lipid microspheres, can ameliorate arthritis in the collagen induced arthritis (CIA) model of rheumatoid arthritis (RA). METHODS: DBA/1J male mice were immunized with bovine type II collagen in adjuvant, and treated daily from onset of clinical arthritis with intravenous administration of lipo-PGE1 (5-50 microg/kg) or lipid vehicle as a control. Arthritis was assessed over a 10 day treatment period by monitoring for paw swelling and clinical score. Histopathology of the arthritic hind paws was also evaluated. Lipo-PGE1 accumulation in arthritic joint tissues was measured using 3H labeled PGE1 incorporated in lipid microspheres. RESULTS: Arthritis was significantly suppressed in lipo-PGE1 treated mice compared with lipid vehicle treated controls (p < 0.05, p < 0.016, respectively) in a dose-dependent manner. Histopathological assessment showed a significant reduction of pannus formation and joint destruction in lipo-PGE1 treated mice compared with controls (p < 0.05). Lipo-PGE1 preferentially accumulated in arthritic joints for a longer period than free PGE1. CONCLUSION: Using an efficient drug delivery system, PGE1 can suppress CIA, and lipo-PGE1 may have a potential therapeutic role in RA.
11695304 [Sweet syndrome in a female patient with intestinal multiple lipomas and diverticular dise 2001 Oct Sweet's syndrome (SS), or acute febrile neutrophilic dermatosis, is a condition characterized by the sudden onset of fever, leukocytosis, and painful, erythematous, well-demarcated papules and plaques which show dense, neutrophilic infiltrates on histologic examination. Myalgias and arthralgias are common. Although it may occur in the absence of other known disease, SS is often associated with hematologic disease (including leukemia), and immunologic disease (rheumatoid arthritis, inflammatory bowel disease). A case of SS is reported. Furthermore the patient presented multiple intestinal lipomas and diverticular colon disease. The authors, on the ground of recent studies which correlate SS with several digestive system disorders, hypothesize an association between acute febrile neutrophilic dermatosis and patient's intestinal diseases. Treatment with systemic corticosteroids is usually successful.
10728453 Development of a Spanish (Castillian) version of the Childhood Health Assessment Questionn 2000 Jan OBJECTIVE: To demonstrate that the Spanish (Castillian) version of the Childhood Health Assessment Questionnaire (cHAQ-S) is a valid and reliable instrument for measuring the health status of children with juvenile chronic (or rheumatoid) arthritis (JCA) and is sensitive to change. METHODS: A conceptual translation of the original questionnaire into Spanish and two back-translations were performed. The cHAQ-S was completed by the parents of young children (aged 1 to 19 years) affected by JCA, and additionally by those children aged over 9. A second cHAQ-S was administered at least 15 months after the first one. RESULTS: The cHAQ-S was administered to 79 patients of patients affected by JCA. The test-retest reliability was evaluated among 16 patients, and no significant differences between the first and second administration were found (0.88 versus 0.84; p > 0.6; intraclass correlation coefficient R = 0.94). The Cronbach's alpha coefficient was 0.948, indicating an excellent internal reliability with a mean correlation between the different components of the questionnaire varying from 0.3557 to 0.7831. For the between-observer reliability, an intraclass correlation coefficient of 0.96 was obtained. Correlations between DI (Disability Index) and several measures of disease activity were all statistically significant (Spearman's R ranged from 0.42 to 0.87; p < 0.005). Patients who improved showed similar improvement in the DI (p = 0.015), while patients who worsened showed a worsening of the DI (p = 0.1) and patients whose condition was stable showed no change in DI (p = 0.6). CONCLUSION: The cHAQ-S is a feasible, reliable and valid instrument for the determination of the health status of Spanish children suffering from JCA. It is also sensitive to changes in the child's health status.
11307318 [Advances in immunoserology tests in clinical medicine: autoantibodies, immune complexes a 2001 Mar I reviewed first the history of detection for autoantibodies and the methods to detect the circulating immune complexes. Then I presented several unusual tests for detecting autoantibodies which I had experienced. They are agglutination tests in agarose gel using the particulate antigens of human tissues or lipid antigens and the mixed agglutination test using the cultured cells. The characteristics of rheumatoid factor(RF) were analyzed by the following methods: 1) solid-phase radioimmunoassay for IgG-RF using the formalinized sheep RBC, 2) mixed agglutination test for IgG-RF on the slide glass smeared with the sensitized sheep RBC, 3) hemolysis in agarose gel for competitive reaction of RF with complement to the IgG hemolysin and 4) ELISA for detecting the complement-fixation of the monoclonal IgM-RF. The IgG-Fc and C3b receptors on the tissue sections of the mammalian aorta were detected by an adhesion of the IgG-sensitized or C3b-bound RBC. DNA-analysis studies using the molecular biology techniques which were done in the Department of Internal Medicine II, Fukushima Medical University were presented. 1) Nucleic acid sequences of the cloned DNA polypeptide fragments in the serum of patients with systemic lupus erythematosus. 2) SSCP analysis for clonality of Vb repertoires in T cell receptors in the patients with rheumatoid arthritis, primary biliary cirrhosis or CREST syndrome. 3) Detection of mRNA of TNFa and Fas ligand in the mononuclear cells(FICL-PCR) in the synovial fluids of RA patients.
9296125 [Late onset myasthenia: 34 cases in patients over 65 years of age]. 1997 Mar This study, a retrospective view of 34 patients with myasthenia gravis, compared the course of the disease for patients with onset before 65 and after 65 years. 70% of those under 65 were female while 55.8% of those over 65 were male. Bulbar symptoms were more frequent in older patients. Only 3 patients had another immune disease (rheumatoid arthritis, diabetes mellitus, thyroid pathology), and two a thymoma. All patients were treated with anticholinesterases. Prednisone was used in 44% of cases and rarely Azathioprine. In our cases and in the review of the literature there is no significant difference between age groups except for the sex ratio and the outcome in the older group in case of thymoma or respiratory failure.
11924920 Stem cell transplantation for autoimmune diseases. 2001 Dec Much progress has been made in the field of haemopoietic stem cell transplants (HSCTs) for severe autoimmune disorders. Theoretical considerations, animal data and anecdotal evidence suggested some time ago that intensive immunoablation followed by autologous HSCT could restore normal immune reactivity in patients with severe autoimmune disorders. Based on a concept statement issued in 1995, two European societies, the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation (EBMT) began collecting phase I/II trial data in an international collaborative network. Sufficient information from more than 350 patients allows a preliminary assessment with level three evidence. Autologous HSCTs can induce remissions in all disease categories tested so far. Remissions can be transient or durable. HSCTs are associated with significant morbidity and mortality. Treatment-related mortality (TRM) is near 10% at 1 year and is associated with the intensity of the conditioning and the stage of the disease at the time of transplant. Marked interdisease differences exist. There are few data available in haematological autoimmune diseases, more in systemic sclerosis (SSc), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA) and multiple sclerosis (MS). Patient selection has been recognized as a crucial element from the phase I-II trials. Patients with advanced disease, severely compromised organ function or irreversible organ damage should not be considered as candidates for HSCT. Prospective randomized studies should now determine the value of HSCT compared to standard therapy. Such trials are ongoing for patients with systemic sclerosis (ASTIS trial--Autologous Stem Cell Transplantation International Scleroderma Trial) or are planned for patients with multiple sclerosis (ASTIMS trial--Autologous Stem Cell Transplantation International Multiple Sclerosis Trial) and rheumatoid arthritis (ASTIRA trial--Autologous Stem Cell Transplantation International Rheumatoid Arthritis Trial). More phase II data are needed for other indications such as SLE and JIA.
11083272 Evaluation of antineutrophil cytoplasmic antibody seroconversion induced by minocycline, s 2000 Nov OBJECTIVE: Case reports have suggested that minocycline, sulfasalazine, and penicillamine are associated with antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. This study evaluated ANCA seroconversion due to these agents in serum samples prospectively collected in randomized, double-blind, controlled trials. METHODS: The sources of study sera were 3 clinical trials: 1) a 48-week trial of minocycline for early rheumatoid arthritis, with 64 patients receiving minocycline compared with 68 receiving placebo; 2) a 37-week trial of sulfasalazine for rheumatoid arthritis, with 51 receiving sulfasalazine compared with 38 receiving placebo; and 3) a 104-week trial of penicillamine for early systemic sclerosis, with 15 undergoing high-dose penicillamine treatment versus 12 receiving low-dose penicillamine. ANCA were measured in the baseline and study-end serum samples by indirect immunofluorescence (IIF) for perinuclear ANCA (pANCA) and cytoplasmic ANCA (cANCA) patterns, and by antigen-specific enzyme-linked immunosorbent assay (ELISA) for antibodies to myeloperoxidase (anti-MPO) and proteinase 3 (anti-PR3). Laboratory personnel were blinded to the group identity of the samples. ANCA results were interpreted using an ANCA scoring system that combines the results of IIF and ELISA testing. RESULTS: No patient in any of the active study drug groups demonstrated ANCA seroconversion according to the final interpretation of the combined IIF and ELISA results. Twelve of the 248 patients (5%) were positive for anti-MPO with pANCA at baseline. No subject was positive for anti-PR3 with cANCA. There were no findings suggestive of vasculitis in any of these patients. CONCLUSION: From our study results, there was no suggestion of ANCA seroconversion induced by minocycline, sulfasalazine, or penicillamine. However, these findings do not rule out the possibility of rare, sporadic cases of either ANCA seroconversion or true drug-induced vasculitis with these drugs.
14622620 Does the peak-end phenomenon observed in laboratory pain studies apply to real-world pain 2000 Autumn Laboratory studies and investigations of patients undergoing painful procedures have compared recalled pain to an average of multiple momentary reports taken throughout the painful experience. This work has shown that recalled ratings of pain are more closely associated with a combination of peak pain and pain proximal to the recall ratings than an average of all momentary reports. However, these studies have examined recalled pain over relatively short periods, usually under 1 hour. In this study of 32 patients with rheumatoid arthritis, momentary pain ratings taken over a 7-day period were compared with pain recalled on the eighth day. Analyses confirmed that a combination of peak and recent pain was a better predictor of recalled patient pain than was a simple average of all momentary pain reports. These results extend our understanding of how individuals remember pain and suggest alternative methods for assessing recalled pain.