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ID PMID Title PublicationDate abstract
10918754 Pediatric autoimmune cardiovascular disease. 2000 Jul Pediatric autoimmune cardiovascular disease can cause serious, sometimes life threatening sequelae on the pediatric population. Valvular, myocardial, and pericardial involvement causing morbidity and mortality can occur in association to rheumatic heart disease, systemic lupus erythematosus, and juvenile rheumatoid arthritis. Serious and potentially life threatening coronary artery involvement can occur in patients with childhood polyarteritis nodosa, Takayasu arteritis, and Kawasaki disease.
10724267 Plastic surgical perspectives on vascular endothelial growth factor as gene therapy for an 2000 Mar The practice of plastic surgery has always remained at the frontier of medical science. Over the past few decades, this frontier has been marked by significant developments in the field of gene therapy. Gene therapy serves to replace, supplement, or manipulate a patient's genetic makeup to restore function that has been lost or to correct function that is aberrant. Recent technology may allow surgeons to augment the processes of wound healing and angiogenesis by transfecting genes encoding desirable proteins, such as vascular endothelial factor (VEGF), into ischemic tissues. VEGF is a vital growth factor in the development of blood vessels. Although its mechanisms of action are numerous, its sole function seems to be the augmentation of angiogenesis. VEGF is active in growth and development, in wound healing, and in various pathologic conditions, such as psoriasis and rheumatoid arthritis. The role of VEGF in the field of plastic surgery is just beginning to be explored; it may someday prove to be very rewarding.
10334506 Esculetin suppresses proteoglycan metabolism by inhibiting the production of matrix metall 1999 Apr 16 The possible mechanism of the chondroprotective effect of 6,7-dihydroxycoumarin (esculetin) was investigated using primary cultures of rabbit articular chondrocytes. Esculetin (EST) significantly suppressed the proteoglycan depletion and the release of pulse-labeled [35S]proteoglycan from the matrix layer of rabbit chondrocytes treated with recombinant human interleukin-1alpha. The matrix metalloproteinase inhibitor, 1,10-phenanthroline, also blocked the proteoglycan depletion and [35S]proteoglycan release. From these results, it is likely that recombinant human interleukin-1alpha-induced proteoglycan depletion is mediated by matrix metalloproteinases. Although esculetin did not directly inhibit collagenolytic activity in the culture media, it significantly suppressed the production of pro-matrix metalloproteinase-1/interstitial procollagenase and pro-matrix metalloproteinase-3/prostromelysin 1, accompanied by a decrease in the steady-state levels of their mRNAs. These results suggest that esculetin is a therapeutically effective candidate for inhibition of cartilage destruction in osteoarthritis and rheumatoid arthritis.
10080877 Identification of TNF-alpha binding peptides from a D-amino acid hexapeptide library that 1999 Jan Tumour necrosis factor alpha (TNF-alpha) is a pro-inflammatory cytokine with pleiotropic activity that binds to two transmembrane receptors. Its role in mediating the inflammatory response to injury or infection has been well documented and it has been shown to be a causative factor in rheumatoid arthritis, inflammatory bowel disease and septic shock. Using synthetic peptide libraries composed exclusively of D-amino acids, two distinct hexapeptide families that block the binding of TNF-alpha to its receptors were identified. In the deconvolution of the library, activity increased from submillimolar to the low micromolar range with the most active compound having an IC50 of 0.33 microM. With the aid of biotinylated constructs of these hexapeptides it was possible to demonstrate that their antagonistic effect is due to specific binding to TNF-alpha and not to its receptor.
10078017 [Non-steroidal antiinflammatory drug--management of gastrointestinal complications and inh 1999 Feb Non-steroidal antiinflammatory drugs (NSAID) are widely used for the treatment of rheumatoid arthritis and other collagen vascular diseases, and now more than 30 drugs are available. However, caution should be paid in using NSAIDs because of their serious side effects, especially gastrointestinal toxicity. Misoprostol has been shown to prevent NSAID-induced gastrointestinal damage, and proton-pump inhibitor omeprazole and misoprostol have been shown to be effective in the treatment of ulcers and erosions induced by NSAIDs. After the discovery of cyclooxygenase-2 (COX-2), investigators have raised a hypothesis that specific inhibitor of COX-2 should have anti-inflammatory activity with least gastrointestinal toxicity. According to this, efforts have been paid to produce COX-2 selective inhibitors. Although several COX-2 inhibitors have been reported to show reduced toxicity, further investigations are needed to establish their usefulness.
11712696 Immunofluorescence--still the 'gold standard' in ANA testing? 2001 A usefulness of enzyme immunoassay (EIA)-based antinuclear antibodies (ANA) tests was evaluated in comparison with the immunofluorescence ANA assay (IF-ANA). COBAS-ANA and MBL-ANA were used, in the former a mixture of antigens extracted from HEp-2 cells and multiple recombinant antigens was immobilized on beads as the antigen, and in the latter 9 kinds of purified or recombinant proteins are immobilized on 96-well plates. We first compared an ability to differentiate 258 connective tissue disease (CTD) patients (except rheumatoid arthritis) from 257 healthy subjects between COBAS-ANA and IF-ANA. The sensitivity and specificity of COBAS-ANA were 84% and 94%, respectively, while those of IF-ANA at a cutoff dilution of 1:160 were 81% and 87%. The receiver operating characteristic (ROC) analysis showed a significant superiority of COBAS-ANA to IF-ANA. Moreover, when the cutoff index was set at 0.6, the COBAS-ANA could detect the 8 disease-specific ANAs as well as IF-ANA at a cutoff dilution of 1:40. A possible availability of MBL-ANA in a periodic health examination in certain towns was also demonstrated. Among the 1123 subjects, a total of 145 disease-specific ANAs were detected in 126 subjects. MBL-ANA could catch disease-specific ANAs with almost same efficacy of IF-ANA. Annual survey of the residents by MBL-ANA may lead to a detection of CTD patients. EIA-based ANA tests are very useful for both detecting disease-specific ANAs and screening CTD patients. We believe that EIA-ANA should be the 'gold standard' especially for screening a large number of samples, although there is some room for technical improvement.
10759405 Matrix metalloproteinase inhibitors: applications in oncology. 1999 Matrix metalloproteinases (MMP) are a group of zinc dependent enzymes which include the interstitial collagenases, stromelysins, gelatinases and membrane-type metalloproteinases. They are involved in the remodelling and turnover of the extracellular matrix proteins. They play a role in wound healing and the pathogenesis of arthritis. In malignancies they play a role in tumor invasion, metastasis and angiogenesis. A number of synthetic matrix metalloproteinase inhibitors (MMPIs) have been developed for clinical use. In preclinical tumor models they have shown promising activity in achieving inhibition of MMPs and reducing tumor growth and metastatic spread. Some have also shown additive or synergistic effects with cytotoxic agents. Phase I and II studies in human subjects have defined the main side effects of these agents as being musculoskeletal pains or arthralgias. As they are cytostatic agents rather than cytotoxic in activity conventional measurements of radiological response for assessment are not applicable in trials. Biological activity has been demonstrated in certain cancers by the effects on levels of tumor markers as surrogate markers of tumor response and also by a fibrotic stromal reaction seen in tumor tissue. Newer agents have been developed with selective inhibition of certain MMPs in an attempt to reduce the side effects. A number of phase III human clinical trials evaluating MMPs are being carried out at present but only one has been formally reported so far. This study suggested that marimastat had no survival advantage when compared to chemotherapy with gemcitabine in advanced pancreatic carcinoma. Current trials are assessing efficacy of MMPIs in maintenance of remission after other modalities of therapy or in combination with cytotoxic agents. MMPs have also been demonstrated to play an important role in the articular cartilage destruction seen in both rheumatoid arthritis and osteoarthritis. The use of MMPIs in both ex vivo and in vivo models have shown promising results and trials are in process to assess their potential role in the control of articular destruction. The true therapeutic role of MMPIs await the results of these randomized studies.
9893572 Evidence of autoantibodies to cell membrane associated DNA (cultured lymphocytes): a new s 1998 Oct OBJECTIVE: Autoantibodies to cell membrane associated DNA are described in systemic lupus erythematosus (SLE). The specificity of these antibodies differ from antibodies to nuclear DNA. METHODS: Using indirect immunofluorescence, a specific IgG was detected giving a characteristic pattern of continuous peripheral membrane fluorescence on cultured B-lymphocytes. RESULTS: This pattern was observed in 53 of 80 serum samples of SLE patients but absent in the serum samples of the control populations: 15 rheumatoid arthritis, 38 ankylosing spondylarthritis, 17 non-inflammatory osteopenic patients, and 224 blood donors. In 34 Sjögren syndrome's patients one only showed a positive test. The cmDNA specificity of these antibodies was confirmed by pattern extinction with DNAse but not RNase or protease pre-treatment of the cells. IgG to cmDNA, separated by absorption/elution from purified cmDNA immobilised on DEAE-nitrocellulose reproduced the immunofluorescence pattern pictures. Extensive serum depletion of anti-double strand or single strand DNA antibodies by absorption to cellulose bound ds- or ss-DNA affected marginally the pericellular fluorescence revealing some minor cross reactivity with nuclear DNA. Moreover, in SLE patients without detectable antibody to ds-DNA, pericellular fluorescence could be visible. CONCLUSION: This novel rapid immunofluorescence method may serve as an identification test of SLE patients. Given its positive (97.1%) and negative (92.9%) predictive value, sensitivity (66%) and specificity (99.5%), it improves on other diagnostic tests such as the detection of antibodies to Sm.
9365095 HLA-B27-derived peptides as autoantigens for T lymphocytes in ankylosing spondylitis. 1997 Nov OBJECTIVE: To study whether peptides derived from the HLA-B27 molecule sequence can stimulate peripheral blood T lymphocytes (PBL) from patients with HLA-B27-associated spondylarthropathies. METHODS: PBL from 55 HLA-B27+ patients with ankylosing spondylitis (AS), 28 HLA-B27+ patients with other spondylarthropathies, 7 rheumatoid arthritis patients, and 30 HLA-B27+ and 22 HLA-B27- healthy controls were tested in lymphocyte proliferation assays with 4 synthetic peptides derived from the HLA-B*2705 molecule. RESULTS: A 13-mer peptide (B27PA) induced significant proliferative responses in 17 of the 55 AS patients (stimulation index [SI] 2.5-17.5), as well as in 3 of the HLA-B27+ healthy controls (SI 2.5-9.8). Another 13-mer peptide (B27PC) induced PBL proliferation (SI 2.7-5.5) in 10 AS patients and in some donors of the control groups. In B27PA-specific T cell lines, an expansion of cells positive for the gamma/delta T cell receptor could be demonstrated. CONCLUSION: These results indicate that HLA-B27-derived peptides can be recognized as autoantigens by PBL of HLA-B27+ AS patients and B27+ healthy controls. Recent infections preceding the manifestation of AS may be involved in this process of anti-self major histocompatibility complex reactivity.
9348140 Polymorphism of the LMP2 gene and disease phenotype in ankylosing spondylitis: no associat 1997 Sep Although a number of reports have now described an association between polymorphism of the LMP2 gene and disease phenotype in HLA-B27 positive individuals with ankylosing spondylitis (AS), some describe associations with acute anterior uveitis, others with juvenile onset disease, and one report provides no association. A recent study describes yet a further association with disease severity in patients with juvenile rheumatoid arthritis. We therefore hypothesized that the discrepant findings in adult disease may be a reflection of an underlying association with disease severity. Our study population consisted of 100 HLA-B27 positive Caucasians with AS of ten or more years duration. Clinical assessment of disease severity was based on a metrology index scoring five measurements, the modified health assessment questionnaire for the spondyloarthropathies, and a disease activity index consisting of a visual analog scale to score the amount of pain, stiffness and fatigue. LMP2 genotypes were assigned following polymerase chain reaction amplification from genomic DNA and restriction enzyme digestion with CfoI. Despite confirmation of a significantly higher prevalence of the LMP2 BB genotype in AAU positive (66.0%) versus AAU negative (45.2%) patients (P < 0.05), we observed no association between LMP2 genotypes and any of the indices of disease severity. Furthermore, although a significant association was noted between the presence of peripheral synovitis and the functional index score (P < 0.05), a history of AAU was not associated with more severe disease. Our data is thus internally consistent in demonstrating no association between LMP2 genotypes and either disease severity or peripheral arthritis, and supports the notion that polymorphism of LMP2 primarily influences the development of AAU and not some other phenotype of AS.
12009077 The TGF beta receptor endoglin in systemic sclerosis. 2001 Dec Immunohistochemical, flow cytometric and ELISA studies were performed to examine the expression of endoglin (CD105, a TGF beta receptor) on dermal endothelial cells, peripheral blood monocytes and free and bound serum levels in patients with systemic sclerosis as compared with appropriate controls. Endoglin was found to be significantly upregulated on dermal blood vessels in patients with scleroderma (and in patients with inflammatory skin disorders) as compared to healthy skin (p < 0.05). In contrast, there was no significant difference in endoglin expression on circulating blood monocytes between scleroderma patients and patients with a rheumatic disoder or healthy control subjects; however, endoglin expression was upregulated on monocytes in inflammatory joint fluid from patients with rheumatoid arthritis. Endoglin expression on monocytes was also influenced by isolation techniques and during whole blood culture. No differences were found in circulating free or bound endoglin levels between scleroderma patients and healthy controls. In conclusion, endoglin expression on dermal endothelial cells was significantly enhanced in scleroderma but levels on circulating monocytes and in the serum were within normal limits. The functional significance of this upregulation is uncertain but may reflect endothelial activation in scleroderma.
11189895 [Complete superficial replacement of the middle finger joint--long-term outcome and surgic 2000 Nov Pain, weakness, malalignment and limited range of motion (ROM) at the PIP joint following arthrosis (degenerative or post-traumatic) or rheumatoid arthritis frequently require surgical treatment. PIP joint fusion or implantation of a prosthetic device are options. The purpose of this study was to report our long-term results with a surface replacement PIP arthroplasty (SR PIP arthroplasty) and the description of our operative technique. 82 prostheses were done in 60 patients between 1980 and 1999. All patients were reexamined, the average follow up was 64 months (12 to 260 months); average age was 57 years. 48 patients were operated on the right hand, 12 on the left hand. 44 patients were female, 16 were male. All patients complained of pain preoperatively. Patients were divided into three groups: A degenerative arthrosis, B posttraumatic arthrosis and C inflammatory arthritis. Active range of motion of all fingers of the operated hand, grip-strength, pain relief, joint stability or deformity and comprehensive radiographic assessment were studied. The subjective impressions of the patients were measured in four grades: very satisfied--satisfied--dissatisfied--very dissatisfied. Finally the investigators divided the overall results in: good--fair--poor. The average flexion arc was 31 degrees (maximum 15 degrees hyperextension to 95 degrees flexion) preoperatively and 47 degrees (maximum 14 degrees hyperextension to 90 degrees flexion) postoperatively. Over 70% of the patients had complete pain relief. In 12 fingers secondary procedures were necessary, usually related to soft tissue deformity and extensor tendon function. No arthrodesis was performed as a following operation. In 40 fingers a good result was achieved (49%), 25 had a fair (30%) and 17 (21%) a poor result. Our results of resurfacing PIP arthroplasty are encouraging and provide equal and usually improved motion in comparison with other joints. With experience and refinements of the operative technique our confidence in surface replacement arthroplasty has increased. For this reason we prefer this procedure for posttraumatic or degenerative arthrosis as against PIP joint fusion or silastic implants.
10446103 High prevalence of NSAID enteropathy as shown by a simple faecal test. 1999 Sep BACKGROUND: The diagnosis of non-steroidal anti-inflammatory drug (NSAID) induced enteropathy is difficult, requiring enteroscopy or the use of four day faecal excretion of (111)In labelled white cells. AIMS: To assess faecal calprotectin (a non-degraded neutrophil cytosolic protein) as a method for diagnosing NSAID enteropathy. METHODS: Single stool faecal calprotectin concentrations were compared with the four day faecal excretion of (111)In labelled white cells in 47 patients taking NSAIDs. The prevalence and severity of NSAID enteropathy was assessed using this method in 312 patients (192 with rheumatoid arthritis, 65 with osteoarthritis, 55 with other conditions) taking 18 different NSAIDs. RESULTS: The four day faecal excretion of (111)In white cells correlated significantly with faecal calprotectin concentrations. In the group of 312 patients on NSAIDs faecal calprotectin concentrations were significantly higher than in controls, the prevalence of NSAID enteropathy being 44%. The prevalence and severity of NSAID enteropathy was independent of the particular type or dose of NSAID being taken or other patient variables. CONCLUSIONS: Assay of faecal calprotectin provides a simple practical method for diagnosing NSAID enteropathy in man. Forty four per cent of patients receiving these drugs had NSAID induced enteropathy when assessed by this technique; 20% of these had comparable levels of inflammation to that previously reported in patients with inflammatory bowel disease.
10047434 The association of anti-Ro52 autoantibodies with myositis and scleroderma autoantibodies. 1999 Mar The presence of autoantibodies to the Ro52 protein in sera from patients with idiopathic inflammatory myopathies has recently been reported. These antibodies were found predominately in sera with the myositis-specific autoantibody anti-histidyl-tRNA synthetase (anti-Jo-1). In this report, we analysed sera from 216 patients to determine whether anti-Ro52 antibodies are associated with myositis autoantibodies other than anti-Jo-1. These included sera containing antibodies that recognize threonyl- or alanyl-tRNA synthetases, Mi-2, PM-Scl, signal recognition particle (SRP), as well as the systemic sclerosis-related antibodies anti-topoisomerase I (Scl-70) and anti-centromere. A high proportion of sera that contain anti-aminoacyl-tRNA synthetase antibodies, anti-SRP, or anti-PM-Scl antibodies were found to contain antibodies to the Ro52 protein. In contrast, in sera containing anti-Mi-2, anti-Scl-70 or anti-centromere antibodies, anti-Ro52 antibodies were absent or occurred infrequently. In addition, only one serum from 41 rheumatoid arthritis patients was positive for anti-Ro52 autoantibodies. These data indicate that anti-Ro52 antibodies are produced in particular subsets of myositis patients, and are not limited to sera with anti-Jo-1 antibodies.
9880449 Malignancies in children who initially present with rheumatic complaints. 1999 Jan OBJECTIVE: Children ultimately diagnosed with malignancy are referred to pediatric rheumatology clinics with provisional rheumatic diagnoses. We aimed to distinguish the features in these patients that lead to the correct diagnosis of malignancy. STUDY DESIGN: A retrospective review of the case records of 29 children (19 boys and 10 girls, aged 1 to 15.5 years) with malignancy who were referred to 2 pediatric rheumatology centers between 1983 and 1997. RESULTS: The suspected diagnoses on referral were: juvenile rheumatoid arthritis (12), nonspecific connective tissue disease (4), discitis (3), spondyloarthropathy (3), systemic lupus erythematosus (2), Kawasaki disease (2), Lyme disease (1), mixed connective tissue disease (1), and dermatomyositis (1). The final diagnoses were leukemia (13), neuroblastoma (6), lymphoma (3), Ewing's sarcoma (3), ependymoma (1), thalamic glioma (1), epithelioma (1), and sarcoma (1). Patients had features typical of many rheumatic disorders including musculoskeletal pains (82%), fever (54%), fatigue (50%), weight loss (42%), hepatomegaly (29%), and arthritis (25%). Features that were suggestive of malignancy included nonarticular "bone" pain (68%), back pain as a major presenting feature (32%), bone tenderness (29%), severe constitutional symptoms (32%), clinical features "atypical" of most rheumatic disease (48%), and abnormal initial investigations (68%). The atypical features included night sweats (14%), ecchymoses and bruising (14%), abnormal neurologic signs (10%), abnormal masses (7%), and ptosis (3%). Initial investigations with abnormal findings included complete blood count/smear (31%), discordant erythrocyte sedimentation rate and platelet count (28%), elevated lactate dehydrognease level (24%), plain skeletal x-ray films (28%), bone scan (21%), and abdominal ultrasonography (17%). Findings of investigations done before referral to the rheumatology clinic were not recognized as abnormal in 11 (40%) patients. CONCLUSIONS: Patients with a diverse group of malignancies, other than leukemia, may present to the pediatric rheumatologist. Pediatric care providers should be familiar with typical features of childhood rheumatic disorders, and rheumatic diagnoses should be reevaluated in the presence of any atypical or discordant clinical features.
9617032 Prospective evaluation of the utilization of aspirin and non-steroidal anti-inflammatory d 1998 Mar The aim of this study was to analyse the frequency of aspirin and NSAID usage in 400 unselected patients admitted to the general medical wards through the Accident and Emergency Department. One hundred and twenty patients (30%) reported using NSAIDs (n = 27) or aspirin (n = 99) prior to admission. The median age was 70.5 years (IQR 54-80). Most aspirin use was low dose for cardiovascular prophylaxis and headache. The reported indications for NSAID use were osteoarthritis (n = 12), rheumatoid arthritis (n = 9), gout (n = 3) and psoriatic arthritis (n = 2) and headache (n = 1). Only 23 (19%) patients were aware of the potential side effects of these agents. Co-prescribing with an H2 antagonist (n = 10), proton pump inhibitor (n = 11) or misoprostol (n = 5) was noted in 21.6%. Approximately one third of patients admitted to general medical wards in this study were receiving NSAIDs or Aspirin. The indications for prescribing were appropriate for aspirin. NSAID use was more symptom based and may have been better managed using an analgesic in some cases. Despite the high prevalence of upper gastrointestinal symptoms, co-prescribing of ulcer healing drugs was relatively uncommon.
10914695 COX-2 specific inhibitors offer improved advantages over traditional NSAIDs. 2000 Jul Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed medications worldwide and are often the first choice of treatment for acute myalgias, orthopedic injuries, postoperative pain, chronic rheumatoid arthritis, and osteoarthritis. The mechanism through which NSAIDs provide analgesia and suppress inflammation is the inhibition of the enzyme cyclooxygenase, resulting in decreased prostaglandin synthesis. The suppression of prostaglandin synthesis can also produce gastric and renal toxicity, as well as impair normal platelet function. Thus, NSAIDs are associated with potentially harmful side effects. Cyclooxygenase exists in two isoenzymatic forms, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Cyclooxygenase-1 appears to be constitutively expressed in many tissues and produces prostaglandins, which regulate normal cellular functions. However, COX-2 activity is induced by proinflammatory cytokines and produces prostaglandins that mediate the inflammatory response and pain signaling transmission. Traditional nonspecific NSAIDs inhibit both COX-1 and COX-2, and in doing so, not only decrease inflammation and pain, but also promote gastrointestinal tract damage and bleeding. The potential clinical benefit of COX-2 inhibitors is significant due to the number of patients chronically treated with NSAIDs and the three- to ten-fold higher risk of gastrointestinal injury and death associated with traditional NSAIDs. Recently, a class of anti-inflammatory medications has been developed that primarily inhibits COX-2 while sparing the enzymatic activity of COX-1 at therapeutic dosages. Two medications that predominantly inhibit only COX-2, rofecoxib and celecoxib, are currently available by prescription in the United States.
10896731 Role of hyaluronan chain length in buffering interstitial flow across synovium in rabbits. 2000 Jul 15 1. Synovial fluid drains out of joints through an interstitial pathway. Hyaluronan, the major polysaccharide of synovial fluid, attenuates this fluid drainage; it creates a graded opposition to outflow that increases with pressure (outflow 'buffering'). This has been attributed to size-related molecular reflection at the interstitium-fluid interface. Chain length is reduced in inflammatory arthritis. We therefore investigated the dependence of outflow buffering on hyaluronan chain length. 2. Hyaluronan molecules of mean molecular mass approximately 2200, 530, 300 and 90 kDa and concentration 3.6 mg ml-1 were infused into the knees of anaesthetized rabbits, with Ringer solution as control in the contralateral joint. Trans-synovial drainage rate was recorded at known joint pressures. Pressure was raised in steps every 30-60 min (range 2-24 cmH2O). 3. With hyaluronan-90 and hyaluronan-300 the fluid drainage rate was reduced relative to Ringer solution (P < 0.001, ANOVA) but increased steeply with pressure. The opposition to outflow, defined as the pressure required to drive unit outflow, did not increase with pressure, i.e. there was no outflow buffering. 4. With hyaluronan-530 and hyaluronan-2000 the fluid drainage rate became relatively insensitive to pressure, causing a near plateau of flow. Opposition to outflow increased markedly with pressure, by up to 3.3 times over the explored pressures. 5. Hyaluronan concentration in the joint cavity increased over the drainage period, indicating partial reflection of hyaluronan by synovial interstitium. Reflected fractions were 0.12, 0.33, 0.25 and 0.79 for hyaluronan-90, -300, -530 and -2200, respectively. 6. Thus the flow-buffering effect of hyaluronan depended on chain length, and shortening the chains reduced the degree of molecular reflection. The latter should reduce the concentration polarization at the tissue interface, and hence the local osmotic pressure opposing fluid drainage. In rheumatoid arthritis the reduced chain length will facilitate the escape of hyaluronan and fluid.
9704652 Autoantibodies to DEK oncoprotein in a patient with systemic lupus erythematosus and sarco 1998 Aug A patient was identified with an unusual autoimmune syndrome consisting of systemic lupus erythematosus and sarcoidosis. Her serum contained extremely high levels of autoantibodies to the DEK protooncogene product. The patient's serum was used to clone a dek complementary DNA, which was expressed as a histidine-tagged fusion protein in Escherichia coli. Using affinity-purified recombinant DEK protein, anti-DEK autoantibodies were found in the patient's serum at a titer of 1:10(6) by enzyme-linked immunosorbent assay (ELISA). Longitudinal studies revealed marked variations in anti-DEK autoantibody levels over time. Although it has been suggested that anti-DEK autoantibodies are a marker for pauciarticular juvenile rheumatoid arthritis with iridocyclitis, the present data suggest that they may be associated with other disease subsets as well. The quantitative ELISA technique will be useful for defining these subsets further and for examining the relationship between anti-DEK titers and disease activity.
11680204 [COX-2 inhibitor non-steroidal anti-inflammatory drugs, myth or reality?]. 2001 Sep The discovery of two isoforms of cyclooxygenase, Cox-1 constitutive and Cox-2 inducible, has prompted the development of new molecules with high Cox-2 selectivity. These new NSAIDs belong to the coxib class and have theoretically a better digestive tolerability than classical NSAID have. In Belgium, rofecoxib ((Vioxx) and celecoxib (Celebrex) are commercialized. Rofecoxib is indicated in the symptomatic treatment of osteoarthritis (12.5 to 25 mg/d) and celecoxib is indicated in osteoarthritis (200 mg/d) and in rheumatoid arthritis (200 to 400 mg/d). Several studies have demonstrated their efficacy, similarly to classical NSAID as diclofenac (Voltaren), naproxen (Naprosyne), ibuprofen (Brufen) and their superiority compared to placebo. Their safety profile for gastrointestinal events is proven in patients without ulcer history compared to classical NSAID. However, the concomitant use of aspirin decreases the benefit as demonstrated for celecoxib at 400 mg/d but not investigated for rofecoxib. The selective inhibition of Cox-2 with no effect on Cox-1 favors cardiovascular events in patients at risk. Other side effects are similar to classical NSAID. Thus Cox-2 inhibitors NSAID are interesting molecules for their sparing gastrointestinal activity. They must be used with caution in patients with ulcer history, in the elderly and in patients requiring aspirin for cardiovascular prophylaxis.