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ID PMID Title PublicationDate abstract
8346415 Lactoferrin triggers in vitro proliferation of T cells of Lewis rats submitted to mycobact 1993 Aug We have recently reported antigenic (B-cell) cross-reactivity between the mycobacterial 65 kDa heat shock protein (hsp65) and human lactoferrin (LF) and we suggested that this cross-reactivity might have a role in mycobacteria-associated autoimmune disease. Here, we have searched for anti-LF T-cell reactivity in Lewis rats submitted to a mycobacteria-triggered autoaggressive disorder (adjuvant arthritis, AA), an autoimmune disorder characterized by high anti-hsp65 reactivity. We have quantified the in vitro proliferative response to LF of lymph node and spleen cells of Lewis rats killed 9, 14 and 21 days after the immunization with the AA-triggering, mycobacteria-containing adjuvant (complete Freund's adjuvant, CFA). We found that LF induced significant proliferation of lymph node T cells of rats undergoing AA. This T-cell proliferation was not as marked as the one provoked by hsp65; it was, nevertheless, significantly higher (P < 0.05) than that produced by a non-arthritogenic antigen (i.e. albumin). T cells from naive or mineral oil (incomplete Freund's adjuvant, IFA) injected rats did not respond to LF or hsp65. These data indicate that LF may work as an accessory stimulatory factor of the T-cell autoreactivity associated with mycobacteria-induced arthritis.
1505108 Proteoglycan structural changes in human rheumatoid articular cartilage. 1992 Mar Human rheumatoid arthritic (RA) cartilage contains elevated levels of proteolytic enzymes in which the metalloproteases are believed to be the prime enzyme system involved in cartilage metabolism. We examined the effects of these enzymes and the serine proteases on endogenous proteoglycans (PGs) and newly synthesized PGs of seven RA cartilages. The data was further analyzed with regard to the therapy received by the patients prior to surgery. A structural heterogeneity among the PGs from RA cartilage was found, and two subsets were distinguished. While in the first subset more than 35% of the PGs were in aggregate form, no appreciable amount of PG aggregate was found in the second subset. Interestingly, in all but one specimen the subsets appeared to be a function of prior therapy received by the patients. In subset I patients had received prednisone and/or DMARD in addition to NSAIDs, while those from subset II had all received NSAIDs only, with one exception. Our findings also suggest that PG structure alterations could result from the action of already active and APMA-activated metalloproteases; these reduced the PG aggregation capability and caused extensive cleavage in the PG core protein. The serine proteases did not seem to play a major role. Moreover, when the endogenous latent metalloproteases were activated with APMA, high-density PGs (the A1D1 fraction) showed a reduction in their capacity to reaggregate, and in their hydrodynamic size. Using an immunological technique we demonstrated the presence, in subset I, of the hyaluronan binding region domain (HABR) of the core protein. For subset II this domain could not be found.(ABSTRACT TRUNCATED AT 250 WORDS)
8630641 Safety of meloxicam: a global analysis of clinical trials. 1996 Apr Meloxicam is a new preferential cyclooxygenase-2 (COX-2) inhibitor for the treatment of rheumatic disease. This paper presents a global safety analysis of data from meloxicam clinical studies, focusing on gastrointestinal (GI) adverse events. Meloxicam 7.5 and 15 mg (n = 893 and 3282) were compared with piroxicam 20 mg (n = 906), diclofenac 100 mg slow release (n = 324) and naproxen 750-1000 mg (n = 243). With respect to all GI adverse events, meloxicam 7.5 and 15 mg were significantly better than all comparators in a pooled analysis of double-blind studies in rheumatoid arthritis (RA) and osteoarthritis (OA). When examining non-serious GI events, severe GI events, discontinuous due to GI events, dyspepsia, abdominal pain and upper GI events, both meloxicam doses were significantly better than comparator non-steroidal anti-inflammatory drugs (NSAIDs) in most cases. Where statistical significance was not demonstrated, there was generally a trend in favour of meloxicam. With respect to upper GI perforations, ulcerations and bleedings, the most serious of NSAID-associated side-effects, meloxicam was better tolerated than the comparators, reaching statistical significance for piroxicam and naproxen. Meloxicam's improved GI safety profile is likely to be due to its preferential inhibition of inducible COX-2 relative to constitutive COX-1.
8490925 Acute and late reactions to radiation therapy in patients with collagen vascular diseases. 1993 Jun 1 BACKGROUND: A commonly held belief is that patients with collagen vascular diseases (CVD) have a greater risk of radiation therapy complications than patients without CVD. This impression is based on anecdotal reports, however. METHODS: A group of 61 patients with CVD were compared with a matched control group of 61 patients without CVD. The CVD group included 39 patients with rheumatoid arthritis (RA), 13 with systemic lupus erythematosus (SLE), 4 with systemic sclerosis (scleroderma) (SSc), 4 with dermatomyositis, and 1 with polymyositis. The control group was matched with respect to age, sex, tumor site and histologic characteristics, treatment aim, general treatment method, radiation therapy technique, site irradiated, radiation dose, date of treatment, and follow-up. RESULTS: Overall, there was no significant difference between the CVD and control groups in terms of acute (11% versus 7%, respectively) or late complications (10% versus 7%, respectively). This was also true when only patients who were treated definitively were considered. Furthermore, none of the patients treated palliatively had complications. Three patients in the CVD group had fatal complications, compared with none in the control group. RA was associated with a slight increase in late complications in the definitively treated patients, whereas SLE was associated with a slight increase in acute reactions. No significant acute or late reactions were observed in the patients with SSc, dermatomyositis, or polymyositis. CONCLUSIONS: In general, these differences are less than expected and not statistically significant. Consequently, from these data, the authors could not show a significant increase in radiation therapy complications for patients with CVD.
1439622 Overall safety of Arthrotec. 1992 Data from four double-blind studies of the treatment of patients with rheumatoid arthritis or osteoarthritis were combined. For 4 to 12 weeks, 747 patients received Arthrotec, a combination of 50 mg of diclofenac and 200 micrograms of misoprostol, and 754 patients received 50 mg of diclofenac; the drugs were given twice or three times daily. The five most commonly reported adverse events were abdominal pain by 23.2% of the diclofenac/misoprostol patients and 19.8% of the diclofenac patients; diarrhea by 19.9% and 11.3%; nausea by 11.8% and 6.5%; dyspepsia by 11.2% and 7.8%; and flatulence by 8.0% and 3.1%. Other adverse events, reported by similar proportions of both treatment groups, included headache, gastritis, dizziness, vomiting, and constipation. In the diclofenac/misoprostol-treated patients, the abdominal pain and diarrhea were rated mild in 30.6% and 24.3%, moderate in 49.1% and 51.4%, and severe in 20.2% and 24.3%. Serious adverse events occurred in eight of the diclofenac/misoprostol-treated patients and in 13 of the diclofenac-treated patients; 12.6% and 10.1%, respectively, were withdrawn from the study because of adverse events. Results of laboratory tests of hepatic and renal function were similar in the two treatment groups.
8835293 Induction and activation of procollagenase in rabbit synovial fibroblasts after treatment 1995 Treatment of rabbit synovial fibroblasts with active oxygen (AO) released by xanthine/xanthine oxidase resulted in an induction of procollagenase in these cells in concentrations ranging from 12.5 micrograms/ml xanthine plus 0.0025 U/ml xanthine oxidase to 50 micrograms/ml xanthine plus 0.01 U/ml xanthine oxidase. Preceding this there was an accumulation of poly(ADP-ribose) for the same concentration range of xanthine/xanthine oxidase. Furthermore, it was found that AO caused activation of the latent procollagenase to the active enzyme in concentrations ranging from 0.1 micrograms/ml xanthine plus 0.00002 U/ml xanthine oxidase to 1 microgram/ml xanthine plus 0.0002 U/ml xanthine oxidase. It is suggested that poly(ADP-ribosyl)ation participates in the induction of procollagenase by relaxing chromatin. Furthermore, it is proposed that AO activates latent procollagenase under physiological conditions.
7954874 Immunodetection of the ribosomal transcription factor UBF at the nucleolus organizer regio 1994 Jun A human autoimmune serum to nucleolus organizer regions (NORs) has been used to localize these structures at the light microscopic level in carp and trout tissue culture cells. In interphase cells, the immunofluorescence pattern indicates that the NORs autoantigens are contained exclusively within the nucleolus of carp epithelial (EPC) and trout gonad (RTG) cells. This fluorescence is punctuate rather than uniform, and presumably represents transcriptional complexes of ribosomal DNA. During mitosis, the autoantigens are detected by immunofluorescence microscopy at the chromosomal nucleolus organizer regions of condensed chromosomes, indicating that a considerable quantity of the molecule(s) remains bound to the ribosomal RNA genes. The major nucleolus autoantigen, defined in mammals as the upstream ribosomal binding factor (UBF), has been identified on immunoblots as a 90 kDa protein in extracts from fish cell lines and tissues. Thus, NORs appear to function as nucleation centers for ribosomal RNA together with a complex set of well-conserved protein factors, such as UBF. Our results suggest evolutionary conservation from fish to mammals with respect to ribosomal RNA biosynthesis driven by RNA polymerase I.
7559694 Prediction of clinical outcome of THR from migration measurements on standard radiographs. 1995 Sep We report the theoretical basis of a method to measure axial migration of femoral components of total hip replacements (THR). The use of the top of the greater trochanter and a lateral point on the collar of the stem, allowing for variations of up to 10 degrees rotation of the femur in any direction between successive radiographs, gave a maximum error of 0.37 mm. At a more realistic 5 degrees rotational variation, the error was only 0.13 mm. These data were confirmed in an experimental study using digitisation of points and special software. We also showed that the centre of the femoral head, the stem tip, and the lesser trochanter provided less accurate landmarks. In a second study we digitised a series of radiographs of 51 Charnley and 57 Stanmore THRs; the mean migration rates were found to be identical. We then studied 46 successful stems with a minimum follow-up of eight years and 46 stems which had failed by aseptic loosening at different times. At two years, the successful stems had migrated by a mean of 1.45 +/- 0.68 mm, but the failed cases had a mean migration of 4.32 +/- 2.58 mm (p < 0.0001). Of the successful cases 76% had migrated less than 2 mm, while in the failed group 84% had migrated more than 2 mm. For any particular case migration of more than 2.6 mm at two years had only a 5% chance of continuing success and would therefore merit special follow-up. Only 24% of the eventually successful stems showed migration at the stem-cement interface, but this had happened in every failed stem. We conclude that it would be possible to evaluate a new cemented design of femoral stem over a two-year period by the use of our method and to compare its performance against the reported known standard of the Charnley and Stanmore designs.
8514202 Natural human antibodies to synthetic peptide autoantigens: correlations with age and auto 1993 Clinically healthy humans as well as patients suffering from various autoimmune diseases produce natural antibodies against a variety of self-components. Such antibodies have been proposed to carry out a physiologic role in maintaining the integrity of self, as well as potentially destructive roles in the generation of autoimmune diseases. Because human autoantigens, particularly membrane proteins, are usually present in extremely small amounts, it is generally impossible to obtain enough to carry out a detailed characterization of the antibodies or the antigenic determinants recognized. To circumvent this difficulty, we developed synthetic autoantigens predicted from the gene sequence of two functionally critical membrane proteins; the band 3 anion transport protein which is found on all cells, and the T-cell receptor (beta chain) which is the antigen-specific receptor on thymus-derived lymphocytes. We have investigated the natural human IgM and IgG antibody responses to peptides selected on the basis of predicted molecular surface exposure and previously known antigenicity, and correlate levels of binding with changes in age and by comparison with autoimmune diseases. We report that the IgM response to synthetic autoantigens tends to be higher than that of IgG molecules, but significant IgG binding occurs to some peptides. This situation is particularly noticeable in comparison of rheumatoid arthritis patients with normal individuals. Distinct peptide portions of individual molecules are recognized differently by the autochthonous immune system as manifested by age dependence of the response and differential levels of IgM and IgG activity. The synthetic autoantigens that tend to generate the highest amounts of natural antibody are those that are either exposed on the surface of the cell (band 3 peptides) or are exposed in the predicted 3-dimensional folding of the molecule (T-cell receptor beta peptides). Rheumatoid arthritis patients tend to give higher IgM reactivities to both band 3 and Tcr beta peptides than do normals, with this effect being less pronounced in the distinct autoimmune disease systemic lupus erythematosus. Studies of normal humans ranging in age from 20 to 90 years suggest two major patterns for the IgM natural antibody response to synthetic peptides giving high response. The first is that the level of IgM reactivity is high early in life and remains high throughout. The second pattern is one in which the reaction is high in younger individuals, but diminishes substantially in the latter decades of life.(ABSTRACT TRUNCATED AT 400 WORDS)
8388691 Atypical autoantigen targets of perinuclear antineutrophil cytoplasm antibodies (P-ANCA): 1993 Apr Atypical antineutrophil cytoplasm antibodies (A-ANCA) are defined here as ANCA detected by IIF and not directed against the predominant ANCA antigens, proteinase 3 (PR3) and myeloperoxidase (MPO). A-ANCA are found in a variety of clinical conditions, namely rheumatoid arthritis, inflammatory bowel diseases, chronic hepatic diseases and several infections including HIV infection. They are directed against a variety of still ill-defined neutrophil antigens and most frequently yield a perinuclear pattern (P-ANCA) of binding by indirect immunofluorescence on ethanol fixed neutrophils. This paper reviews the literature on A-ANCA and our recent data suggesting that, among others, cathepsin G is one of the predominant antigen targets of A-ANCA. From a clinical point of view, the distinction between MPO-ANCA and A-ANCA is not possible by indirect immunofluorescence (IIF). The determination of ANCA antigens by specific ELISA is therefore necessary to differentiate P-ANCA with MPO specificity from those with undefined specificity. This is of importance because the clinical value of MPO-ANCA is clearly established while the presence of A-ANCA is difficult to interpret given their occurrence in a large variety of clinical conditions.
8697616 Transforming growth factor-beta (TGF-beta) expression and interaction with proteinase 3 (P 1996 Jul TGF-beta is a multifunctional cytokine modulating the onset and course of autoimmune diseases as shown in experimental models. The aim of this study was to investigate TGF-beta expression in ANCA-associated vasculitis (AAV), and the possible interactions of this cytokine with lysosomal enzymes identified as ANCA autoantigens (e.g. PR3). This included TGF-beta effects on the translocation of the lysosomal enzymes to the cell surface of polymorphonuclear neutrophils (PMN), and the presumed activation of non-bioactive, latent TGF-beta by these enzymes. Patients with various types of systemic vasculitis (SV) were studied, including three different types of AAV (Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS) and microscopic polyangiitis (MPA)). Regardless of the type of assay applied, the TGF-beta 1 isoform was found to be over-expressed in SV, including AAV, and to correlate with disease activity as shown for WG. Mean TGF-beta 1 plasma levels in AAV patients ranged from 8.9 ng/ml (WG) to 13.3 ng/ml (CSS) (control 4.2 ng/ml; P < 0.01), while TGF-beta 2 levels were not elevated. Flow cytometry analysis showed TGF-beta 1 to be a potent translocation factor for PR3 comparable to other neutrophil-activating factors such as IL-8. PR3 membrane expression on primed PMN increased by up to 51% after incubation with TGF-beta 1. PR3 itself was revealed as a potent activator of latent TGF-beta, thus mediating bioeffects of this cytokine. These findings, together with other features of TGF-beta such as induction of angiogenesis and its strong chemotactic capacity, indicate that TGF-beta might serve as a proinflammatory factor in SV, especially in AAV.
7487370 Influence of various forms of dialyzable leukocyte extracts on rat adjuvant arthritis. 1994 Adjuvant-induced arthritis in rats is a chronic inflammatory disease, widely used as an animal model for rheumatoid arthritis. In our study the effect of various fractions of dialyzable leukocyte extract (DLE): DLE I-molecular weight below 10 kDa (commercial preparation), DLE II-molecular weight below 5 kDa (suppressor fraction), DLE III-molecular weight 5-10 kDa on rat adjuvant-induced arthritis was studied. The adjuvant arthritic (AA) rats were treated with DLE fractions i.p. in solutions containing an active substance isolated from 12.5 x 10(6) and 6.25 x 10(6) leukocytes from day 1 (adjuvant injected) through day 18, every second day (total 9 times). Various markers of inflammation, immune function and joint destruction were evaluated: hindpaw volume, serum hyaluronic acid, serum albumin and biopterin in urine. All these markers showed a significant improvement after using fraction DLE II in comparison with AA controls. Fractions DLE I and DLE III influenced only some markers of inflammation and immune function. Our results demonstrated a therapeutical effect of fraction DLE II on rat adjuvant-induced arthritis.
1352723 Variations among rheumatologists in prescribing and monitoring of disease modifying antirh 1992 Jul One hundred consultant rheumatologists were sent a questionnaire on their prescribing pattern, and dose and monitoring schedules of four disease modifying antirheumatoid drugs (DMARDs). Seventy-five completed questionnaires were received. Sulphasalazine was the most popular first choice DMARD. There was general agreement on dose schedules which were similar to those recommended in the data sheets although for each drug a minority used different dose schedules. There was, however, marked variation among respondents in what was accepted as an adequate trial of therapy, in monitoring schedules and in the interpretation of results of toxicity monitoring. In many cases these practices differed significantly from the data sheet recommendations. These differences in stated practice could have financial and medicolegal as well as clinical implications.
7558136 Synovial fibroblasts as accessory cells for staphylococcal enterotoxin-mediated T-cell act 1995 Jul Rheumatoid arthritis (RA) is thought to be the result of T-cell-mediated autoimmune phenomena. So far, a critical autoantigen has not been identified. Recently, superantigens have been implied in the pathogenesis of RA. In the present study it was tested whether major histocompatibility complex (MHC) class II-positive synovial fibroblast cells (SFC) function as superantigen-presenting cells. SFC were stimulated with interferon-gamma (IFN-gamma) to express class II antigens; then they were cultivated in the presence of T cells with or without staphylococcal enterotoxins (SE). T-cell activation was measured as proliferation and interleukin-2 (IL-2) production. Depending on the dose and type of SE, activation of T-cell clones and also of peripheral T cells was seen. T-cell activation was inhibited by antibodies to MHC class II antigens and also by antibodies to intracellular adhesion molecule type-1 (ICAM-1). The data suggest that class II-positive SFC have the capacity to serve as accessory cells for superantigen-mediated T-cell activation. Thus SFC may participate in the propagation of a T-cell dependent immune response.
8900554 Risk factors for serious nonsteroidal-induced gastrointestinal complications: regression a 1996 Mar OBJECTIVES: This analysis evaluated the clinical and demographic risk factors for a suspected, serious nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) complication in everyday clinical practice and calculated the risk reduction associated with misoprostol therapy in these "at-risk" patients. METHODS: Using logistic regression analysis, the data set from a randomized, parallel, placebo-controlled trial of misoprostol in 8,843 rheumatoid arthritis patients taking NSAIDs (the Misoprostol Ulcer Complications Outcomes Safety Assessment trial) was modeled to identify risk factors for GI adverse events. The dependent variable was defined as a "suspected serious GI complication," and the independent variables included demographic features, level of functional disability, presence of co-morbid diseases, use of certain drugs, and treatment arm. RESULTS: Two hundred forty-two suspected serious GI complications were observed; 102 occurred in the misoprostol treatment group (risk: 2.32%) and 140 in the placebo group (risk: 3.15%). Overall risk reduction due to misoprostol therapy was 26.6% (confidence interval 5.5%-42.9%, P < .05). However, in patient groups with identified risk factors, misoprostol use decreased the risk for an adverse GI event by 38.3%-87.3%. Specifically, those who benefitted significantly from therapy with misoprostol were patients with a history of peptic ulcer disease (risk reduction 52.4%), history of previous GI bleeding (risk reduction 50%), history of significant cardiovascular disease (risk reduction 38.3%), significant functional disability (risk reduction 87.2%), and patients whose symptoms required concomitant antacid use (risk reduction 48.3%). CONCLUSION: We conclude that in everyday practice, patients who require chronic NSAID therapy and who have specific clinical risk factors may benefit from misoprostol co-therapy.
1445445 Regulation of synovial cell growth. Coexpression of transforming growth factor beta and ba 1992 Nov OBJECTIVE: To demonstrate expression of transforming growth factor beta (TGF beta) and basic fibroblast growth factor (bFGF) by cultured rheumatoid arthritis (RA) synovial cells and to investigate their role as synovial cell mitogens. METHODS: Polypeptide growth factors were detected and identified by immunocytochemical staining and Western blot analysis. Messenger RNA (mRNA) transcripts encoding TGF beta and bFGF were identified by polymerase chain reaction analysis. The influence of neutralizing growth factor monoclonal antibodies (MAb) on RA synovial cell growth was investigated. TGF beta bioactivity was determined by Mv1Lu assay. RESULTS: Lysates of RA, as compared with normal, synovial cells contained greater amounts of TGF beta and bFGF. Western blot analysis identified a single TGF beta band (MW approximately 25 kd) in each of the cell lysates examined. Western blot analysis using MAb DE6 identified a doublet of bFGF bands (MW approximately 18.0 kd) in normal synovial cell lysates and 4 bFGF bands (MW approximately 18.0, 22.0, 22.6, and 25.2 kd) in RA synovial cell lysates. RA and normal synovial cells expressed mRNA transcripts encoding TGF beta 1 but not TGF beta 2, and FGF-2 (basic FGF). Additional mRNA transcripts encoding FGF-5 and FGF-7 were expressed by RA, but not normal, synovial cells in culture. In contrast to MAb 1D11.16, which caused a dose-dependent decrease in RA synovial cell growth, MAb DG2 (up to 100 micrograms/ml) had no effect on cell growth. CONCLUSION: RA and normal synovial cells cultured in serum-free medium express TGF beta 1 and native bFGF. However, only RA synovial cells in culture express higher molecular weight isoforms of bFGF. TGF beta 1 appears to regulate synovial cell growth in vitro through an external autocrine loop. Despite expression of high-affinity bFGF receptors on cultured synovial cells, the mechanisms by which bFGF modulates synovial cell growth are unknown.
8635373 Pulmonary function in patients receiving long-term low-dose methotrexate. 1996 Apr STUDY OBJECTIVE: Acute interstitial pneumonitis is the main pulmonary side effect during methotrexate (MTX) treatment for rheumatoid arthritis. The aim of the study was to determine the following: (1) the incidence of MTX-induced pneumonitis during low-dose long-term MTX treatment for chronic arthritis; (2) whether periodic pulmonary function tests were useful for detecting MTX pneumonitis before clinical symptoms; and (3) whether any subclinical abnormality of pulmonary function was present in asymptomatic patients receiving MTX treatment. DESIGN: Pulmonary function tests, including diffusing capacity for carbon monoxide (DCO) measurements, were performed in 124 patients receiving low-dose MTX for rheumatologic diseases at the time of initiating treatment, and then at 3 months, 6 months, and at 6-month intervals thereafter. Mean duration of treatment was 23 months. RESULTS: MTX treatment was interrupted in six patients for acute onset of clinical symptoms; criteria for diagnosis of MTX pneumonitis were fullfilled in four cases (incidence: 3.2%); no risk factor could be identified. No significant decrease in pulmonary function parameters could be observed before the onset of clinical symptoms of MTX pneumonitis, and this adverse effect could not be predicted by periodic function tests. A statistically significant decrease was found in FVC (-2.2%, p=0.04), FEV1 (-5.0%, p<0.001), and diffusing capacity per alveolar volume, DCO/VA (-4.8%, p=0.03), but not DCO (-1.3%, p>0.05), in the 118 other asymptomatic patients during MTX treatment. CONCLUSION: We found minor subclinical alterations in pulmonary function in asymptomatic patients receiving low-dose long-term MTX treatment, but periodic pulmonary function tests did not allow us to detect MTX-induced pneumonitis before clinical symptoms. Therefore, we recommend that these tests should not be systematically performed while patients are receiving treatment.
8025224 Ureteral stenosis due to recurrent Wegener's granulomatosis after kidney transplantation. 1994 Feb The ureter is an unusual location for lesions of Wegener's granulomatosis (WG). A patient in whom recurrence of WG after kidney transplantation was manifested by obstructive uropathy due to granulomatous vasculitis (WG) at the ureterovesicle anastomosis, as well as nasal and lung involvement, is reported. The occurrence of WG in the ureter in relation to the processes causing ureteral obstruction and the recurrences of WG after kidney transplantation and its treatment are briefly reviewed.
8823424 Microstomia does not necessarily mean scleroderma. 1996 Aug Two patients with microstomia in the absence of any features of progressive systemic sclerosis are documented. Follow-up of almost 20 years did not reveal development of any features of this disease. The first patient had systemic lupus erythematosus and the second rheumatoid arthritis/Sjögren's syndrome with a complicating myositis.
8172230 Pathogenesis and treatment of the anemia of chronic disease. 1994 May The anemia of chronic disease may be viewed simply as the anemia that accompanies chronic inflammatory, infectious, or neoplastic disorders. Because these conditions are very common, the anemia of chronic disease is one of the most frequent anemias encountered, and is only second in incidence to iron-deficiency anemia. The anemia of chronic disease is primarily an anemia due to underproduction of red cells, with low reticulocyte production, and is most often a normochromic, normocytic anemia. However, in 30% to 50% of patients, the red cells are hypochromic and microcytic and, most often, the serum iron, total iron-binding capacity, and transferrin saturation are reduced in the presence of adequate iron stores. Although the differential diagnosis includes other underproduction anemias, such as those caused by vitamin and mineral deficiencies, renal failure, endocrinopathies, and myelodysplasia, it generally is easily distinguished from these conditions. Nevertheless, an understanding of the pathogenesis of this condition, as well as a means of alleviating the anemia when the chronic disorder persists, has remained elusive. Recently, major advances have occurred toward understanding the pathogenesis of the anemia of chronic disease and its treatment, and these advances are reviewed.