Browse

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

ID PMID Title PublicationDate abstract
1527609 The influence of transoral odontoid resection on stability of the craniovertebral junction 1992 Oct Twenty-seven cases of craniovertebral junction compression treated with transoral surgery were reviewed to assess the influences of pathological processes and surgical interventions on spinal stability. All patients presented with signs and symptoms of spinal-cord or brain-stem dysfunction. Pathology included rheumatoid arthritis in 11 patients, congenital osseous malformations in 11, spinal fractures in two, plasmacytoma in one, osteomyelitis in one, and a gunshot injury in one. Instability was defined as clear radiographic evidence of mobile subluxation in conjunction with clinical assessment. Of 19 patients (70%) requiring internal fixation, nine underwent upper cervical fusion and 10 had occipitocervical fusion. When instability occurred, all subluxations were at the C1-2 level. There were no occipito-atlantal subluxations. Eight patients (30%) had preoperative instability of the craniovertebral junction due solely to their pathology, 11 patients (40%) suffered instability after transoral surgery, and eight (30%) were without clinical or radiographic evidence of instability (mean follow-up period 14 months). Craniovertebral junction instability predominated among patients with rheumatoid arthritis: 91% required fusion and 45% presented with pre-existing instability. Among individuals with congenital osseous malformations, 45% required fusion and only one patient (9%) had pre-existing instability. Patients who required subsequent posterior decompression of a Chiari malformation were at risk for developing instability; three of four became unstable after posterior decompression. Transoral resection of the dens, the anterior arch of C-1, and the lower clivus does not fully destabilize the spine; however, this operation may potentiate incipient pathological instability. The primary determinants of instability are the extent of pathological bone destruction, ligamentous weakening, and operative bone removal. Long-term follow-up monitoring is needed after transoral surgery to detect cases of late instability.
7638864 DR4Dw4/DR53 molecules contain a peptide from the autoantigen calreticulin. 1995 Apr Rheumatoid arthritis (RA) occurs more frequently in HLA-DR4+ individuals than in those who do not express this MHC class II molecule. Although the role of this genetic factor in the immunopathology of this autoimmune disease is unclear, the association of RA with HLA-DR4 may indicate that DR4 molecules present autoantigen(s) to T cells. Here we report the analysis of naturally processed peptides, eluted from a mixture of HLA-DR4Dw4 (DRB1*0401) and DR53 (DRB4*0101) molecules isolated from an RA patient-derived EBV-transformed B cell line. Several (size variants of) self-peptides originating from the autologous molecules HLA-A2, HLA-Cw9, HLA-B62, HLA-DR4Dw4 and HLA-DR53, were identified. We also found a sequence that has no homology to any protein in the SwissProt protein sequence databank, and a peptide identical to an internal fragment of the autoantigen calreticulin. The association of the identified peptides with cells expressing HLA-DR4Dw4/DR53 was confirmed by peptide binding analysis. In agreement with previously described peptide binding motifs for DR4Dw4, most peptides contained an aromatic residue (Phe, Tyr, Trp) at relative position i and a small hydroxyl-containing residue (Ser, Thr) at i + 5. Our findings indicate that in RA patient-derived EBV-transformed B cells DR4Dw4/DR53 molecules present a peptide from the autoantigen calreticulin. Interestingly, autoantibodies against calreticulin have been found in various rheumatic diseases, including rheumatoid arthritis. Thus, the analysis of HLA class II-bound peptides can lead to the identification of putative T helper epitopes, which might be involved in the immunopathology of autoimmune diseases.
1577070 Peptide recognition, T cell receptor usage and HLA restriction elements of human heat-shoc 1992 May A commonly held postulate regarding the etiology of rheumatoid arthritis (RA) is that of antigenic mimicry. Recent interest has focused on the mycobacterial 65-kDa heat-shock protein (hsp) as a putative causal agent. The 65-kDa hsp has over 40% sequence homology with the human hsp 60, and elevated synovial T cell responses to both antigens have been demonstrated in RA and juvenile rheumatoid arthritis patients. Such T cells should, therefore, be specific for shared epitopes on the two antigens. To investigate this, we screened synovial fluid mononuclear cells from two early RA patients with peptides of the 65-kDa hsp which have the greatest homology with the human hsp 60. We also raised a panel of T cell clones from one of the patients with the 65-kDa hsp. The synovial T cell population from both patients and one of the T cell clones recognized a peptide representing the amino-acid sequence 241-255. This clone also responded to the peptide of the equivalent human sequence, and was restricted by HLA-DQ. A second T cell clone recognized an adjacent epitope (amino acid sequence 251-265) which is also highly homologous with the human sequence, but this clone was restricted by HLA-DR. The clones utilized different V beta gene segments but the same D beta and J beta gene elements, and both exhibited specific cytotoxicity against autologous antigen-pulsed macrophages. Our findings, therefore, do not disagree with the postulate that autoimmune disease could possibly be triggered by bacterial epitopes with homology to self protein. However, it is also noted that there are alternative interpretations of this data.
8856610 Novel mechanisms of selective apoptosis in synovial T cells of patients with rheumatoid ar 1996 Aug OBJECTIVE: To analyze whether T cells infiltrating the synovium of patients with rheumatoid arthritis (RA) express functional Fas antigen. METHODS: Mononuclear T cells, mainly from synovial tissues, synovial fluids (SF), and peripheral blood mononuclear cells (PBMC) from 14 patients with RA and 5 with osteoarthritis (OA), were treated with anti-Fas monoclonal antibody (Mab) (CH11) for 24 h in vitro. Cell viability and DNA fragmentation were examined. The expression of Fas antigen, Fas ligand, and T cell subpopulations was examined using flow cytometry and reverse transcription polymerase chain reaction. RESULTS: More than 50% of T cells from synovial tissue and SF of patients with RA underwent apoptosis, whereas no effect was observed in PBMC from RA or PBMC and synovial T cells from OA, suggesting that functional Fas antigens are specifically expressed on synovial T cells. Flow cytometric analysis demonstrated higher expression of Fas antigen in T cells from RA synovium than from PBMC. The T cell subpopulations susceptible to anti-Fas Mab were mainly CD45RO+ and CD4 or CD8 single positive T cells, indicating that activated mature T cells express functional Fas antigen. Fas ligand was overexpressed only in synovial nonadherent cells in RA at the level of mRNA, whereas T cells account for more than 60% of the total, but not in OA. CONCLUSION: These findings suggest the majority of activated T cells infiltrating the synovium express functional Fas antigen and Fas ligand specifically in patients with RA but not OA. This phenomenon may provide a clue to understanding the pathogenesis of RA.
8732122 [Clinical and experimental study on sustained release tablet of Tripterygium wilfordii in 1996 Jan Adopt to the prospective, multi-center, random, single-blind, equal rank-control methods, 226 patients of rheumatoid arthritis diagnosed according to the ARA criteria, were divided into 2 groups. One hundred and fourteen patients of test group were treated with sustained release tablets of Tripterygium wilfordii (TW-SR) orally, 2 tablets, twice a day for 4 weeks, 112 patients of control group received tablets of Tripterygium wilfordii (TW) orally, 2 tablets 3 times per day for 4 weeks. Results showed that the total effective rate of the two groups were 92.11% and 90.65%, respectively (P > 0.05). The adverse reaction rate of TW-SR group was 20.18%, which was lowered than that of TW group (70.54%, P < 0.01). Results of pre-clinical pharmacologic experimental study showed that the TW-SR has obvious anti-inflammatory, analgesia and immunosuppress'ive action as the TW has, while its toxicity was less than the latter significantly.
8586764 A case of drug eruption caused by the crude drug Boi (Sinomenium stem/Sinomeni caulis et R 1995 Oct We report a case of drug eruption caused by the crude drug Boi. A 41-year-old female patient had been diagnosed with chronic rheumatoid arthritis in the department of internal medicine. After ingestion of a decoction of the crude drug Boi for the alleviation of arthralgia, a slight fever developed, which was followed by systemic edematous erythema with itching. HPLC showed that the main components of the crude drug Boi are sinomenine and magnoflorine. The results of patch tests were negative for all oral drugs that the patient had been taking. Oral ingestion tests showed that the patient showed positive reactions to the as-is Boi boiling-water decoction and 1/10-volume sinomenine. Based on this, the drug eruption was judged to be caused by sinomenine. It is considered the first time that the causative component of a drug eruption was confirmed by oral ingestion tests with components of a crude drug of Kampo medicine (Sino-Japanese traditional medicine).
7579790 beta 1,4-Galactosyltransferase activity in B cells detected using a simple ELISA-based ass 1995 Jun Lymphocytic beta 1,4-galactosyltransferase (beta 1,4-GalTase, EC 2.4.1.38) activity was measured in B cells using a neoglyco-protein, N-acetylglucosamine-phenylisothiocyanate-bovine serum albumin (GlcNAc-pITC-BSA), as an acceptor substrate in a novel enzyme-linked immunosorbent assay (ELISA)-based method. This assay proved to be much simpler to use than the lengthy and expensive radiochemical assays commonly used, and has the additional advantage that it specifically detects the enzyme mediating transfer via the Gal beta 1,4GlcNAc linkage. A F(ab')2 antibody against GalTase was able to specifically inhibit the reaction. Greater sensitivity for beta 1,4-GalTase activity was obtained using GlcNAc-pITC-BSA as an acceptor substrate rather than ovalbumin. Low levels of beta-galactosidase activity were detectable in lymphocyte cell lysates at acidic pH, although such activity was not detectable at the neutral pH used in the beta 1,4-GalTase activity assay. Using this assay with the GlcNAc-pITC-BSA acceptor, similar beta 1,4-GalTase activities were observed in CD19+ B cells from patients with rheumatoid arthritis (RA) to those seen in normal control individuals.
8388364 Human cartilage aggrecan CS1 region contains cryptic T-cell recognition sites. 1993 Apr Cartilage proteoglycan aggregates (PG) are candidate T-cell autoantigens in the pathogenesis of rheumatoid arthritis (RA). We have investigated the possibility that responses to class II-restricted T-cell recognition sites in human cartilage aggrecan (core protein) may depend upon whether these sites are available as free peptide antigens or as part of intact monomers. Analysis of mouse T-cell responses to intact or deglycosylated monomers, purified from human articular cartilage, and to synthetic peptides of the chondroitin sulphate (CS) attachment region homologous repeat sequence showed that recognition of T-cell epitopes in the CS1 region was strongly dependent upon the form of antigen used. The results show that the CS1 region contains cryptic T-cell recognition sites and raise the possibility that fragments of PG, released through the action of extracellular proteases in inflamed joints, may be capable of activating T cells with specificities for epitopes which are not made available following processing of intact PG. T cells with specificities for cryptic epitopes in PG may play a role in the pathogenesis of RA.
1588758 [Adult Still's disease]. 1992 Mar Still's disease was reported to be a type of Juvenile Rheumatoid Arthritis (JRA) by Still in 1897. Adult-onset Still's disease is an important clinical entity inducing fever, skin rash and polyarthritis. Spiking fever and rash are characteristic features for early diagnosis. Although chronic polyarthritis is similar to RA, ankylosis of hand joint is characteristic for Still's disease rather than destructive change. Increased ESR, negative autoantibodies, leukocytosis, liver dysfunction and hyperferritinemja are major laboratory findings. A markedly increased level of serum ferritin can be used, not only as an indicator of disease activity, but also as a diagnostic marker of the disease. For therapy, a moderate dose of steroid is the most effective.
7932425 A longterm endoscopic evaluation of patients with arthritis treated with nabumetone vs nap 1994 Jun OBJECTIVE: To compare the gastrointestinal safety, ulcerogenic potential, and clinical efficacy over 5 years of nabumetone and naproxen therapy, in patients with rheumatoid arthritis (RA) or osteoarthritis (OA). METHODS: Fifty-two patients entered a randomized, double blind study. Patients were randomized to 3 months treatment with either nabumetone, 1000 mg nightly, or naproxen, 250 mg twice daily, followed by an endoscopist-blind 5-year followup study. After the double blind phase, 15 patients in the nabumetone group and 12 in the naproxen group continued in the longterm endoscopist-blind phase. Endoscopic evaluations for gastroduodenal damage and global assessments of arthritis activity and degree of pain for efficacy were measured. RESULTS: Over the 5-year period, endoscopically visible gastroduodenal ulceration was found in 8 of the naproxen treated patients compared with one of the nabumetone treated patients (p = 0.02). There was a significant difference in the time to develop an ulcer, with a greater risk of developing an ulcer sooner while taking naproxen (p < 0.01). Patients in both groups reported significant improvements in arthritis symptoms (p < 0.01). CONCLUSION: Nabumetone appears to have a significantly lower ulcerogenic potential than naproxen over a 5-year period, and there is a trend toward better tolerability as measured by withdrawals for adverse experiences.
8348276 An evaluation of the Health Assessment Questionnaire in long-term longitudinal follow-up o 1993 Aug We have used the Health Assessment Questionnaire (HAQ) to follow changes in disability in an unselected group of 245 patients with RA. The HAQ has been widely used in cross-sectional studies of disability in RA, but little is known about the dynamics of the change in HAQ score with long term follow-up. If it is to prove useful as a measure of health outcome it must not only be able to accommodate a wide range of disability but also show adequate sensitivity to change in disability. We administered the HAQ to 245 RA inpatients and outpatients at the beginning and end of a 5-yr period to address this important question. The mean change in individual HAQ score in the 175 patients for whom complete data was available was +0.18 (SD 0.66) over 5 yr, i.e. 0.03 units per year. It is likely that the observed rate of change in HAQ score is an under-estimate of the true rate of progression of disability, as the scale failed to accommodate change in disability toward its upper limit. The inherent design of the HAQ creates several 'ceilings' in functional subcategories (such as lower limb function) which may be masked by the overall HAQ score. Longitudinal studies of disability using the HAQ as outcome measure should therefore be interpreted with caution, and close attention paid to the baseline HAQ score.
7679467 Restricted immunoglobulin variable region gene usage by hybridoma rheumatoid factors from 1993 Feb Rheumatoid factors (RFs) are autoantibodies that are produced by approximately 75% of patients with rheumatoid arthritis (RA). Their role in pathogenesis is not well understood. In this study of 81 human hybridoma IgM antibodies derived from unstimulated peripheral blood B-cells of patients with RA and systemic lupus erythematosus (SLE), we have demonstrated that idiotypes associated with RFs derived from patients with mixed cryoglobulinemia were expressed by approximately 60% of RFs and 6% of IgM antibodies lacking RF activity. The specificity of the RFs for the Fc portion of IgG only (monospecificity) or for Fc and additional self antigens (polyreactivity) was found to correlate with the expression of specific heavy chain associated idiotypes. The VH3 associated RF idiotypes, D12 and B6, were expressed by 0/16 (0%) of monospecific RFs compared with 6/22 (27%) of polyreactive RFs. The predominant use of VH3 was verified by analysis of the expressed Ig with VH family specific anti-peptide antibodies. The light chains expressed by both populations of IgM RFs were found to be predominantly VKIII, both by detection of specific epitopes/idiotypes and V family analysis. This non-random gene usage of both the heavy and light chains suggests that there is a selective expression of V regions in the RF producing B-cells in patients with RA and SLE. We suggest that different antigen-driven, clonal selection events may occur which result in either monospecific RFs or polyreactive RFs.
8083354 Functional profile of tissue-infiltrating and circulating CD68+ cells in giant cell arteri 1994 Sep Macrophages represent a critical component in the inflammatory lesions of giant cell arteritis. By combining immunohistochemistry and in situ hybridization, we have analyzed the functional heterogeneity of tissue-infiltrating macrophages in patients with untreated vasculitis. 20% of macrophages in temporal artery tissue synthesized IL-6-specific mRNA and produced IL-6 and IL-1 beta proteins. IL-6 and IL-1 beta production was not limited to CD68+ cells in the lymphoid aggregates but was a feature of CD68+ cells dispersed throughout the tissue. 50% of tissue-infiltrating CD68+ cells synthesized 72-kD type IV collagenase. Only a small subset of CD68+ cells produced cytokines as well as collagenase, indicating functional specialization or distinct differentiation stages of CD68+ cells in the inflamed tissue. Activation of CD68+ cells was not restricted to tissue-infiltrating cells. Expression of IL-6 and IL-1 beta was found in 60-80% of circulating monocytes of patients with untreated giant cell arteritis, whereas collagenase production was restricted to tissue macrophages. IL-6 and IL-1 beta production by the majority of circulating monocytes was a shared feature of patients with giant cell arteritis and polymyalgia rheumatica but was not found in rheumatoid arthritis. These data suggest that giant cell arteritis has two components of disease, an inflammatory reaction in vessel walls and a systemic activation of monocytes. Systemic monocyte activation can manifest independently without vasculitis as exemplified in patients with polymyalgia rheumatica.
7572329 Application of intensified (+) Qi Gong energy, (-) electrical field, (S) magnetic field, e 1995 Jan Various methods of improving circulation and enhancing drug uptake which were used in treating some intractable medical problems caused by infections, and two syndromes based on the co-existence of Chlamydia trachomatis infection (mixed with either Lyme Borrelia burgdorferi or Cytomegalovirus) with increased Uric acid are described. The principal author's previous studies have indicated that there are two opposite types of Qi Gong energy, positive (+) and negative (-). Positive (+) Qi Gong energy has been used clinically to enhance circulation and drug uptake in diseased areas where there is a micro-circulatory disturbance and drug uptake is markedly diminished. (-) Qi Gong energy has completely the opposite effect and therefore has not been used although there may be some as yet undiscovered application. Since the late 1980's the principal author has succeeded in storing (+) Qi Gong energy on a variety of substances including small sheets of paper, and recently has been able to intensify this energy by concentrating it as it passes through a cone-shaped, tapered glass or plastic object placed directly on the (+) Qi Gong energy stored paper. Application of (+) Qi Gong energy stored paper on the cardio-vascular representation area of the medulla oblongata at the occipital area of the skull often improved circulation and enhanced drug uptake. If the drug-uptake enhancement was still not sufficient for the drug to reach therapeutic levels in the diseased organ, direct application of (+) Qi Gong from the practitioner's hand often enhanced the drug uptake more significantly. However, this direct method often results in the practitioner developing intestinal micro-hemorrhage within 24 hours which may or may not be noticed as mild intestinal discomfort with soft, slightly tarry stool. For intensifying (+) Qi Gong energy one of the most efficient shapes is a cone with increased intensification occurring at an optimal height. However when the total mass and the total distance from base to peak is increased beyond an optimal limit, the power decreases. Clinical application of Intensified (+) Qi Gong stored energy was evaluated in this preliminary study which indicated that intensified (+) Qi Gong energy application on the heart representation area of the middle finger on the hands markedly improved circulation in the corresponding organ, and increased drug uptake and acetylcholine even more effectively than some of the previously used drug enhancement methods (Shiatsu massage of the organ representation areas and/or application of (+) Qi Gong energy stored paper to the occipital area above the cardiovascular representation area of the medulla oblongata).(ABSTRACT TRUNCATED AT 400 WORDS)
8313670 Bronchiolitis in association with connective tissue disorders. 1993 Dec In general, lung involvement in connective tissue disorders has not been as well defined as has isolated interstitial lung disease; this applies particularly to bronchiolitis, which occurs infrequently. The low prevalence of bronchiolitis may reflect difficulties in making the diagnosis in mild to moderate disease; at present, most reported disease is severe. This is likely to account for the lack of therapeutic success in obliterative bronchiolitis and in many patients with follicular bronchiolitis. There is a need for earlier intervention if treatment is to be effective, and thus there is a need to refine the noninvasive diagnosis of bronchiolitis. This goal is unlikely to be achieved without the systematic noninvasive evaluation and surveillance of large groups of patients with connective tissue diseases. The role of the pulmonary function laboratory in identifying early bronchiolitis remains entirely uncertain; whether silent "small airways disease," defined physiologically, predicts the eventual development of bronchiolitis is unclear. The reversibility of this asymptomatic lesion with inhaled steroid therapy and the role of inhaled treatment in bronchiolitis, in general, have not been evaluated. More work needs to be done to determine the predictive value of CT appearances and BAL findings, to try to identify a subgroup of patients at greater risk of developing severe bronchiolitis. Further histocompatibility studies may serve as a basis for the selection of patients with an increased likelihood of developing airways disease. The role of open lung biopsy requires further clarification. Better noninvasive evaluation should reduce the need for this invasive procedure; in some patients, however, including those with concomitant interstitial lung disease, histologic assessment will remain an essential component of management. In recent years, in contrast to early reports, it has become apparent that organizing pneumonia has a better prognosis than fibrosing alveolitis in the connective tissue diseases; overall, stability or regression of disease, usually with corticosteroid therapy, was documented in 28 of 39 reported cases. In these patients, a tissue diagnosis serves to identify the need for aggressive therapeutic intervention. Finally, the compilation of larger clinical series would improve our understanding of severe bronchiolitis. This is likely to require multicenter collaboration, which often is impracticable; without this approach, however, the description of bronchiolitis will remain anecdotal.
8381155 Characterization of the T cell receptor repertoire causing collagen arthritis in mice. 1993 Feb 1 Collagen type II-induced arthritis (CIA) is generated in susceptible rodent strains by intradermal injections of homologous or heterologous native type II collagen in complete Freund's adjuvant. Symptoms of CIA are analogous to those of the human autoimmune disease, rheumatoid arthritis. CIA is a model system for T cell-mediated autoimmune disease. To study the T cell receptor (TCR) repertoire of bovine type II-specific T cells that may be involved in the pathogenesis of CIA in DBA/1Lac.J (H-2q) mice, 13 clonally distinct T cell hybridomas specific for bovine type II collagen have been established and the alpha and beta chains of their TCRs have been analyzed. These T cell hybridomas recognize epitopes that are shared by type II collagens from distinct species and not by type I collagens, and exhibit a highly restricted TCR-alpha/beta repertoire. The alpha chains of the TCRs employ three V alpha gene subfamilies (V alpha 11, V alpha 8, and V alpha 22) and four J alpha gene segments (J alpha 42, J alpha 24, J alpha 37, and J alpha 32). The V alpha 22 is a newly identified subfamily consisting of approximately four to six members, and exhibits a high degree of polymorphism among four mouse strains of distinct V alpha haplotypes. In addition, the beta chains of the TCRs employ three V beta gene subfamilies (V beta 8, V beta 1, and V beta 6), however the V beta 8.2 gene segment is preferentially utilized (58.3%). In contrast, the J beta gene segment usage is more heterogeneous. On the basis of the highly limited TCR-alpha/beta repertoire of the TCRs of the panel of bovine type II-specific T cell hybrid clones, a significant reduction (60%) of the incidence of arthritis in DBA/1Lac.J mice is accomplished by the use of anti-V beta 8.2 antibody therapy.
7594514 Localization of an Fc-binding reactivity to the constant region of human IgG4. Implication 1995 Nov 15 The majority of plasma cells in rheumatoid arthritis (RA) synovium produce rheumatoid factors (RF). IgG RF predominate in the immune complexes found in RA synovial fluid and have been implicated in the pathogenesis of RA. IgG4 RF are a major component of IgG RF produced in serum and synovium of RA patients, even though this subclass comprises only 4% of the serum IgG. We produced an IgG4 mAb, hRF-1, with RF reactivity from the synovial tissue of a patient with RA. mAb hRF-1 had binding specificity for mammalian IgG similar to Staphylococcus aureus protein A, which is characteristic of RF from patients with RA. To determine the molecular basis of this particular RF reactivity, the heavy and light chain genes of mAb hRF-1 were amplified by PCR, cloned, and ligated into the pSG5 plasmid for expression in COS-7 cells. Chain recombination experiments localized the Fc-binding reactivity to the hRF-1 heavy chain. Using a series of chimeric Ab sequences, the Fc-binding reactivity was mapped to the constant region of IgG4 rather than the variable region involved in classic RF reactivity. Multiple domains, including Hinge, CH2, and CH3 of the IgG4 constant region were required for Fc binding. Our studies demonstrate an example of RF-like Fc-binding reactivity that is conferred by the gamma-4 constant region rather than the classic Ag binding site and suggest that increased production of IgG4 may contribute to the pathogenesis of RA.
7816776 Biopharmaceutical aspects of tolfenamic acid. 1994 The pharmacokinetics of tolfenamic acid is well described by a two-compartment model with relatively short half-lives (T/2 beta 1-2 hours) and tolfenamic acid is highly protein-bound with small volumes of distribution. It is cleared relatively fast (150-200 ml/min), mainly by hepatic metabolism and the metabolites are renally cleared as glucuronic acid conjugates. The peroral absorption is good and the peroral bioavailability is about 75%, as first pass metabolism accounts for about 20%. Tolfenamic acid shows linear pharmacokinetics and during multiple dosage regimen, i.e. thrice daily, no accumulation beyond the second dose is observed. The bioavailability in dependence of age and disease has been studied and only in the case of severe liver or kidney impairment, a change in dosage regimen seems warranted. The development of different formulations will be outlined, mainly on rectal delivery, on sustained release and rapid release oral formulations, on topical ointment, and on parenteral delivery. The problems with tolfenamic acid in pharmaceutical formulation caused mainly by poor solubility will be discussed. Formulations ready for the market now or very soon are Clotam capsules (tablets). Clotam retard tablets, Clotam suppositories, and Clotam oral suspension, whereas rapid tablets, topical ointments, and parenteral formulations need further development to be ready for marketing in the years to come.
8803910 The role of anti-malarials in rheumatoid arthritis--the American experience. 1996 Jun Rheumatoid Arthritis (RA) is a chronic disease with significant morbidity and functional disability. The traditional treatment for RA relied on the use of NSAIDs early in the disease course, followed by disease-modifying agents later. More recently, the disease-modifying anti-rheumatic drugs (DMARDs) have become the mainstay of RA therapy because of the recognition of their superior efficacy/toxicity profile. The antimalarial drugs, chloroquine and hydroxychloroquine, are some of the most commonly used DMARDs in the management of RA. They have been shown to be significantly more effective than NSAIDs alone in several clinical trials, and have a benign toxicity profile. A combination of hydroxychloroquine with methotrexate appears to reduce significantly the hepatic toxicity of methotrexate. In this review, we summarize the efficacy and toxicity profiles of the antimalarial drugs in rheumatoid arthritis.
7492754 Comparison of anti-TNF alpha autoantibodies in plasma and from EBV transformed lymphocytes 1995 To examine the ability of normal and autoimmune individuals to produce circulating anti-TNF alpha antibodies, plasma samples from 10 RA patients, 10 SLE patients and 5 normal subjects were assessed for anti-TNF alpha antibody. While every individual tested demonstrated circulating IgM anti-TNF alpha antibody, IgG anti-TNF alpha autoantibody was seen predominantly in autoimmune patients. Only 1 of 5 normal individuals, but 15 of 20 autoimmune individuals had plasma IgG anti-TNF alpha antibodies. To examine the ability of normal and autoimmune individuals to produce anti-TNF alpha autoantibody from their circulating lymphocytes, EBV transformation was performed. Oligoclonal immortal cell lines were successfully established from 13 patients and each one secreted detectable IgM anti-TNF alpha autoantibody. Transformed cells from only 1 of 5 normal individuals secreted IgM anti-TNF alpha autoantibody. These results indicate a higher prevalence of anti-TNF alpha autoantibody production among autoimmune individuals although normal individuals are also capable of producing these autoantibodies.