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ID PMID Title PublicationDate abstract
12078053 [Serum leptin levels in patients with rheumatoid arthritis are correlated with body mass i 2002 May Leptin, a 16-kD protein of the ob gene product, is produced by adipose tissue and acts on the hypothalamus to suppress neuropeptide Y secretion which reduces the appetite. It has been demonstrated that serum leptin levels in healthy subjects are correlated with body mass index(BMI). Leptin is also produced by stimulation of inflammatory cytokines such as tumor necrosis factor(TNF)-alpha and interleukin(IL)-1. Rheumatoid arthritis(RA) is one of the chronic inflammatory diseases in which high serum cytokine levels are noted. In this study, we measured serum leptin levels(s-leptin) by RIA kit in 20 healthy subjects (10 males and 10 females) and 49 RA patients(14 males and 35 females) and the markers for joint inflammation such as ESR and CRP. There was no difference in s-leptin between controls(male: mean +/- SD = 5.6 +/- 3.0 ng/ml; female: 7.8 +/- 4.5 ng/ml) and RA patients(male: 4.9 +/- 3.2 ng/ml; female: 9.1 +/- 5.7 ng/ml). S-leptin was correlated with BMI in both healthy subjects and RA patients. However, there was no correlation between s-leptin and the values of ESR or CRP, disease stages in RA patients. In conclusion, s-leptin in RA patients reflects BMI but not joint inflammation.
12572373 [Clinical observation on treatment of rheumatoid arthritis by combined therapy with methot 2002 Aug OBJECTIVE: To observe the effect of Fengshi No. 1 (FS1) in treating patients with active stage of rheumatoid arthritis (RA). METHODS: Patients with RA were randomly divided into two groups, the 40 patients in the treated group were treated with combined therapy of methotrexate (MTX), sulfasalazine (SSZ) and FS1, and the 20 in the control groups were treated with MTX and SSZ alone. RESULTS: In the treated group, the total effective rate was 97.5%, the clinical controlled and markedly effective rate 95.0% and the occurrence rate of side-toxic reaction 10.0%, as compared with those in the control group, 60.0%, 20.0% and 45.0% respectively, the difference was significant (chi 2 = 11.91, 32.23 and 7.67 respectively, all P < 0.01). The effect in the treated group was superior to that in the control group in abating joint swelling and pain, improving function of joint, reducing immune indices and ameliorating iconographic features (P < 0.01 or P < 0.05). CONCLUSION: FS1 not only has the effects of anti-inflammation, analgesis, regulating immune reaction, but also could retard the occurring of bone destruction, reduce the toxic-side effects of MTX and SSZ.
12379521 Measuring the meaning of disability in rheumatoid arthritis: the Personal Impact Health As 2002 Nov BACKGROUND: Measurement of disability in rheumatoid arthritis is often used to support treatment decisions and outcome assessments, but is used without reference to the impact of disability on individual patients. OBJECTIVE: To develop and validate a scale to measure individual values for functions, which is used to weight the level of an individual patient's functional loss and thus calculate the personal impact of disability. METHODS: In four linked studies, first the phraseology for values was explored to develop a stem question for the value scale couched in terms patients understand (face validity). Then short and long versions of the value scale were compared (content validity) and tests of internal consistency and short term reliability undertaken (criterion validity). Finally, the value scale was examined for long term reliability and agreement with expected variables (criterion and construct validity), after which personal impact scores were calculated and their construct validity examined. RESULTS: Patients understand the concept of values, and a positively phrased stem question was developed for the value scale, for which a short version was reasonably equivalent to a long version. The value scale was reliable over one week (96% changed by <1 point) with positive interitem correlation. Reasonable six and 12 month reliability was shown (52% changed by <0.5 points), and the value scale was independent of disability and clinical, psychological, personality, and social support variables. Personal impact scores were then calculated by using the value scores to weight disability scores. Impact scores varied widely between patients of similar disability. Personal impact for disability showed convergent validity with dissatisfaction with disability, perceived increase in disability, increased disease activity, worse psychological status, low social support, and time trade off for disability. It discriminated between patients with low and high dissatisfaction with disability, life satisfaction, depression, pain, and helplessness. CONCLUSION: This individualised personal impact scale should lend meaning to disability scores, improving the interpretation of clinical and research data.
12358374 Analysis of cartilage-derived retinoic-acid-sensitive protein (CD-RAP) in synovial fluid f 2002 Sep We have measured the concentration of cartilage-derived retinoic-acid-sensitive protein (CD-RAP) in synovial fluid (SF) from the knees of 49 patients with osteoarthritis (OA) and 79 with rheumatoid arthritis (RA) in order to investigate the correlation between the type of joint disease and level of CD-RAP. The mean concentration of CD-RAP in synovial fluid was significantly higher in OA than in RA. The level of CD-RAP in the group of patients with mild OA was significantly higher than in the moderate or severe groups and that in the group with mild RA was also significantly higher than in the other RA groups and decreased with progression of the disease. Immunohistochemical studies showed expression of CD-RAP in the cytoplasm of chondrocytes in newly-formed fibrocartilage. Since CD-RAP is mainly produced in young and proliferating chondrocytes, our results suggest that the level of CD-RAP in synovial fluid reflects remodelling of articular cartilage and may be used as a marker to estimate objectively the restorative reaction of chondrocytes.
15320768 Therapeutic potential of hammerhead ribozymes in the treatment of hyper-proliferative dise 2004 Aug The limited efficacy of current therapeutic approaches for a number of socially relevant human diseases such as cancer and cardiovascular pathologies, has required the exploration of alternative and more effective therapeutic strategies. In the last two decades, nucleic acid based drugs have emerged as an attractive and novel alternative with great therapeutic potential. Among these molecules, hammerhead ribozymes were the first to be extensively studied and predicted to be of potential practical utility. Hammerhead ribozymes are catalytic RNA molecules capable of inducing the site-specific cleavage of a phosphodiester bond within an RNA molecule. Thus, they can be used to reduce the intracellular level of a specific mRNA coding for a protein which affects cellular metabolism or environment, causing disease. As hammerhead ribozymes can be engineered to reduce the level of virtually any mRNA, they have a very broad applicability. Among the several pathological conditions amenable for a hammerhead ribozyme based therapeutic approach, we focused our attention on pathologies sustained by a dis-regulated and excessive cellular proliferation, being sure to properly demonstrate their usefulness. Trying to be as objective as possible in regard to the feasibility of hammerhead ribozyme employment as therapeutics, a technical section, describing some of the unresolved problems in this field, has been also included. Although some aspects of hammerhead ribozymes as therapeutics can and should be optimized, the encouraging results displayed so far fully justifies further efforts, economic and scientific, to bring them closer to the clinical practice.
15479869 Should contemporary rheumatoid arthritis clinical trials be more like standard patient car 2004 Nov The information used by rheumatologists when delivering care to patients with rheumatoid arthritis (RA) is derived mainly from two sources: randomised controlled clinical trials and experience in clinical care. However, these two sources differ significantly because (a) the extensive inclusion and exclusion criteria result in clinical trial participants being recruited from only a minority of patients seen in standard clinical care; (b) assessments in clinical trials are conducted according to standard quantitative measures and indices, while standard clinical care of most patients with RA is generally conducted empirically, without collection of any quantitative data other than laboratory tests to estimate prognosis and document change in status; and (c) although baseline databases of various clinical trials (and observational studies) are 60-90% identical in content, they are not standardised and therefore not amenable to direct comparisons. Strategies to promote similarities between clinical trials and standard clinical care in patients with RA may include: more generalised inclusion criteria; incorporation of quantitative measurement into standard care, easily accomplished by asking each patient to complete a simple questionnaire at each visit to a rheumatologist; and consensus among rheumatologists for databases with standard content and format in clinical care and research involving patients with RA.
14501231 Acute secondary gastrointestinal amyloidosis in a patient with rheumatoid arthritis. 2003 Sep Secondary amyloidosis is well recognized as a severe complication in the late stages of rheumatoid arthritis (RA). However, there have been few reported cases of secondary amyloidosis developing early during the course of RA. We here report the case of a 35-year-old woman, in whom RA who had been diagnosed 1 year before, with intractable watery diarrhea as a symptom of RA-induced secondary intestinal amyloidosis. Combination treatment with intravenous hyperalimentation, corticosteroids, and methotrexate (MTX) resulted in a dramatic improvement of her symptoms and objective findings of serological abnormalities. Subsequent administration of corticosteroids and MTX resulted in long-term survival without recurrence. This case indicates that we should be alert for the development of secondary amyloidosis, even in patients with a short history of RA, when the disease is active. Furthermore, combination therapy with intravenous hyperalimentation and strong immunosuppressive agents seems to be very efficacious in the treatment of RA-associated secondary intestinal amyloidosis.
11908553 Norepinephrine from synovial tyrosine hydroxylase positive cells is a strong indicator of 2002 Mar OBJECTIVE: Density of sympathetic nerve fibers in synovial tissue was lower in patients with rheumatoid arthritis (RA) compared to those with osteoarthritis (OA). This was accompanied by norepinephrine (NE) release from synovial tyrosine hydroxylase positive cells (TH+ cells). We investigated the role of TH+ cells and NE in synovial inflammation. METHODS: Synovial tissue of 34 patients with RA and 36 with OA who underwent knee joint replacement surgery was characterized using immunohistochemistry and a synovial tissue superfusion technique, respectively. In culture experiments with mixed synoviocytes, the effect of NE on secretion of interleukin 6 (IL-6), IL-8, tumor necrosis factor (TNF), and matrix metalloproteinase-3 (MMP-3) was investigated. RESULTS: Tissue density of TH+ cells was higher in RA compared to OA (63.9 vs 34.2 cells/mm2; p = 0.017). Basal NE release from synovial tissue correlated highly significantly with density of TH+ cells in RA (Rrank = 0.573, p = 0.001) but not in OA (Rrank = 0.102, NS). Basal NE release correlated with the degree of inflammation in RA (Rrank = 0.420, p = 0.021) but not in OA (Rrank = 0.174, NS), and with spontaneous IL-8 secretion in RA (Rrank = 0.581, p = 0.001) but not in OA (Rrank = 0.160, NS). Only in RA, density of TH+ cells correlated positively with spontaneous secretion of IL-6, IL-8, and MMP-3. We confirmed the extensive loss of sympathetic nerve fibers in RA compared to OA (0.32 vs 3.1 nerve fiber/mm2; p < 0.001). The ratio of sympathetic to sensory nerve fibers was 1 to 5 in RA and 2 to 1 in OA. A ratio of 1.0 separates almost all patients into 2 diseases groups (RA vs OA). Prior prednisolone treatment of RA patients was related to decreased spontaneous cytokine secretion, a lower density of T cells, CD163+ macrophages and TH+ cells, a lower degree of inflammation, and reduced synovial NE secretion. NE was able to inhibit secretion of IL-6 (in OA), IL-8 (in RA), and TNF (in RA and OA) in culture experiments. CONCLUSION: TH+ cells and release of NE are strongly linked to a higher degree of synovial inflammation. Culture experiments indicate that NE has antiinflammatory properties at higher concentrations (10(-5) M). NE secretion of TH+ cells may be an antiinflammatory mechanism to counteract local inflammation. Thus, TH+ cell derived NE can be an important local factor of immunomodulation in synovial inflammation.
11920396 Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 recepto 2002 Mar OBJECTIVE: To evaluate the efficacy and safety of anakinra in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA). METHODS: Patients with moderate-to-severe active RA who were receiving MTX for 6 consecutive months, with stable doses for > or = 3 months (those with disease duration of >6 months but <12 years) were randomized into 6 groups: placebo or 0.04, 0.1, 0.4, 1.0, or 2.0 mg/kg of anakinra administered in a single, daily, subcutaneous injection. The primary efficacy end point was the proportion of subjects who met the American College of Rheumatology 20% improvement criteria (attained an ACR20 response) at week 12. RESULTS: A total of 419 patients were randomized in the study. Patient demographics and disease status were similar in the 6 treatment groups. The ACR20 responses at week 12 in the 5 active treatment plus MTX groups demonstrated a statistically significant (P = 0.001) dose-response relationship compared with the ACR20 response in the placebo plus MTX group. The ACR20 response rate in the anakinra 1.0-mg/kg (46%; P = 0.001) and 2.0-mg/kg (38%; P = 0.007) dose groups was significantly greater than that in the placebo group (19%). The ACR20 responses at 24 weeks were consistent with those at 12 weeks. Similar improvements in anakinra-treated subjects were noted in individual ACR components, erythrocyte sedimentation rate, onset of ACR20 response, sustainability of ACR20 response, and magnitude of ACR response. Anakinra was safe and well tolerated. Injection site reaction was the most frequently noted adverse event, and this led to premature study withdrawal in 7% (1.0-mg/kg group) to 10% (2.0-mg/kg group) of patients receiving higher doses. CONCLUSION: In patients with persistently active RA, the combination of anakinra and MTX was safe and well tolerated and provided significantly greater clinical benefit than MTX alone.
12519610 Celecoxib for rheumatoid arthritis. 2002 BACKGROUND: Rheumatoid arthritis (RA) is a systemic auto-immune disorder, involving persistent joint inflammation. NSAIDs are used to control the symptoms of RA, but are associated with significant gastro-intestinal toxicity, including a risk of potentially life threatening gastroduodenal perforations, ulcers and bleeds. The NSAIDs known as the selective Cox II inhibitors, of which celecoxib is a member, were developed in order to reduce the GI toxicity, but are more expensive. OBJECTIVES: To establish the efficacy and safety of celecoxib in the management of RA by systematic review of available evidence. SEARCH STRATEGY: We searched the following databases up to August 2002: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment Database. The bibliographies of retrieved papers and content experts were consulted for additional references. SELECTION CRITERIA: All eligible randomised controlled trials (RCTs) were included. No unpublished RCTs were included in this edition of the review. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers. Data was analysed using a fixed effects model. A validated checklist was used to score the quality of the RCTs. The planned analysis was to pool, where appropriate continuous outcomes using mean differences and dichotomous outcomes using relative risk ratios. This was not however possible due to the lack of data. MAIN RESULTS: Five RCTs were included (4465 participants); three of the studies also enrolled individuals with OA. The comparators were placebo, naproxen, diclofenac and ibuprofen. The evidence reviewed suggests that celecoxib controls the symptoms of RA to a similar degree to that of the active comparators examined (naproxen, diclofenac and ibuprofen). When compared to placebo, the percentage of patients showing improvement according to ACR 20 criteria at week 4 were 42/82 (51%) in the twice daily celecoxib 200mg group and 43/82 (52%) in the twice daily celecoxib 400mg group; these were significantly different from the placebo group in which 25/85 (29%) improved. The six month data reviewed support a reduced rate of UGI complications with celecoxib but there is also evidence to suggest that these benefits may not be evident in the long-term and that celecoxib offers no additional benefit in patients who are also receiving cardio-prophylactic low dose aspirin. REVIEWER'S CONCLUSIONS: For an individual with RA the potential benefits of celecoxib need to be balanced against the uncertainty that the short-term reduced incidence of upper GI complications are maintained in the long-term and its increased cost in comparison to traditional NSAIDs.
15171811 History and diagnostic value of antibodies to citrullinated proteins in rheumatoid arthrit 2004 May Rheumatoid arthritis is a chronic inflammatory joint disease characterized by the presence of autoantibodies. The best known autoantibody is the rheumatoid factor. Another group of antibodies directed against citrullinated epitopes is proven to be more specific for rheumatoid arthritis. This review gives an overview of the history of the different anti-citrullinated protein antibody detection methods and their diagnostic and prognostic properties in RA.
15077260 Use of mainstream nonpharmacologic treatment by patients with arthritis. 2004 Apr 15 OBJECTIVE: To examine the use of nonpharmacologic treatment by patients with osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: Patients were recruited from physicians' offices in Ontario, Canada. All participants completed questionnaires that asked about their health status, use of medications and nonpharmacologic treatments, and use of health care resources. RESULTS: A total of 326 patients with OA and 253 patients with RA completed the survey on the use of nonpharmacologic treatment. Only 73% of patients with OA had been told to use nonpharmacologic modalities, but 98.8% had tried at least 1 type of treatment. About 97% of those with RA had been told to use and had tried at least 1 type of treatment. Most patients continued to use a treatment once they had tried it. CONCLUSION: The use of nonpharmacologic modalities is common among patients with arthritis. It is important that clinicians address with their patients the appropriate use of and barriers to continuing these treatments.
12604376 Incidence of rheumatoid nodule in Dalmatia: similarities and differences among populations 2003 Jan BACKGROUND: The specific aim of our study was neither prognosis nor long-term evaluation but focus on determining incidence of rheumatoid nodules (RN) in a large population of patients with rheumatoid arthritis (RA) on the coastline of Croatia (Dalmatia) within a certain range. We compared our data with those published previously in the literature. METHODS: Our study was focused on determining incidence of RN occurrence in patients with rheumatoid arthritis in Dalmatia, Croatia by comparing these figures with data reported elsewhere and evaluating its importance in the process of diagnosing RA. The duration of the study was 10 years (1991-2001). There were 421 patients (344 women and 77 men) with confirmed RA diagnosis. Median follow-up time was 2 years (range: 1.4-3.5 years). RESULTS: Existence of RN was established by clinical examination in 109 of 421 patients; incidence density was 17.3%. RN occurred somewhat more frequently in men (32%) as compared to women (24%) without statistically significant difference. In 38% of patients, RN occurred simultaneously in several sites, more frequently in men (64%) than in women (30%) (odds ratio [OR] 2.13, p <0.05). Correlation of seropositivity and RN appearance was very high: positive in 84% of patients with nodules as compared to 58% of patients without nodules (OR 1.45, p <0.05) with no statistically significant differences between sexes. CONCLUSIONS: Results obtained warrant the conclusion that RN incidence in our patients from Dalmatia is comparable with results of earlier Croatian studies as well as with Western European figures and Caucasian population data reported on other continents. RN incidence differs significantly for Asian and Arabian populations, i.e., is less frequent, and for the U.S. population, where it is more frequent.
11998897 Oral administration of gammalinolenic acid, an unsaturated fatty acid with anti-inflammato 2002 Mar Administration of gammalinolenic acid (GLA), an unsaturated fatty acid, reduces joint inflammation in patients with rheumatoid arthritis. Addition of GLA in vitro suppresses release of interleukin-1beta (IL-1beta) from human monocytes stimulated with lipopolysaccharide (LPS). LPS-induced IL-1beta release is followed by IL-1-induced IL-1beta release, an amplification process termed "autoinduction." We show here, using IL-1alpha stimulation to simulate autoinduction, that administration of GLA to healthy volunteers and to patients with inflammatory arthritis reduces LPS-induced IL-1beta secretion mainly by reducing autoinduction of IL-1beta. GLA reduces LPS-induced pro-IL-1beta mRNA modestly and IL-la-induced pro-IL-1beta gene expression markedly. In addition to reducing amplification of IL-1beta, GLA increases the amount of IL-1 receptor antagonist (IL-1Ra) secreted from stimulated cells, thereby facilitating an increase in the secreted IL-1Ra/IL-1beta ratio. IL-1beta is important to host defense, but the amplification mechanism may be excessive in genetically predisposed individuals. Thus, reduction of IL-1beta autoinduction may be protective in some patients with endotoxic shock and with diseases characterized by chronic inflammation.
12017854 [Ultrasound diagnosis of inflammatory diseases of the hand and elbow]. 2002 Mar After clinical and radiological examination, ultrasound has an important place in the diagnostic procedures for patients with chronic inflammatory diseases. Synovitis and effusion of the joint can be documented. Sonography may be helpful in providing an earlier diagnosis. Erosive lesions of the articular surface in the sonographic field of view can be detected at a very early stage, often when the clinical and radiological examinations are still unremarkable. This may lead to an earlier start of drug therapy or an earlier indication for operative treatment. Sonography gives a good impression of the inflammatory changes of the elbow joint and the distribution of synovitis and joint effusion in the different parts of the joint. It is a good method to document the therapeutic effects. The sonographic echogenicity of the muscle of rheumatoid patients seems to change. Synovitis and effusion of the hand can be documented with ultrasound. Infiltration of the synovitis into the tendon could not be visualized. The sonographic diagnostic accuracy in tendon ruptures of the hand was reduced in comparison with the clinical examination. Whether ultrasound will be an efficient method to identify patients at risk for a tendon rupture will be seen with further developments of the technical possibilities.
15464974 Effects of IL-1beta on gene expression in human rheumatoid synovial fibroblasts. 2004 Nov 5 IL-1 is one of the key mediators involved in the pathogenesis of rheumatoid arthritis (RA) and is known to affect the level of gene expression in various settings. We investigated the effects of IL-1beta on the expression of 240 genes in rheumatoid synovial fibroblasts (RSFs) using a cDNA microarray. Total RNAs were prepared from RSFs stimulated with IL-1beta and hybridized to the microarray. The fluorescence intensity of each gene was compared between the control and IL-1beta-treated cells. To confirm the data obtained from the microarray analysis, the level of gene expression was also examined by ELISA, Northern blot, or Western blot depending on the genes to be analyzed. The genes whose levels were significantly changed by IL-1beta in the microarray analysis could be divided into three categories; inflammatory mediators, matrix-modifying enzymes, and apoptosis-associated molecules. The increase in the mRNA levels of IL-6, IL-8, MCP-1, and GRO-1 was confirmed by determining their protein levels from the cell culture supernatant using ELISA. The increase in the level of two matrix-degrading enzymes, MMP-1 and MMP-3, was reproducibly observed by an ELISA method, while the decrease in the level of TIMP-3, an inhibitor of MMPs, was confirmed by Northern blot analysis. The fluorescence intensity of two apoptosis-related genes, caspase-3 and Bcl-xL, was significantly lowered. The decreased protein level of caspase-3 was also found. Our data suggested that IL-1beta could provoke a series of responses in RSFs leading to the pathologic status of RA, including enhancement of inflammatory cytokines, imbalanced production of MMPs and TIMPs, and dysregulation of apoptosis.
12010565 Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: integration 2002 Matrix metalloproteinase (MMP)-1, MMP-8 and MMP-13 are interstitial collagenases that degrade type II collagen in cartilage; this is a committed step in the progression of rheumatoid arthritis and osteoarthritis. Of these enzymes, the expression of MMP-1 and MMP-13 is substantially increased in response to IL-1 and tumor necrosis factor-alpha, and elevated levels of these collagenases are observed in arthritic tissues. Therefore, cytokine-mediated MMP-1 and MMP-13 gene regulation is an important issue in arthritis research. In this review, we discuss current models of MMP-1 and MMP-13 transcriptional regulation, with a focus on signaling intermediates and transcription factors that may be future targets for the development of new arthritis drugs.
15215020 Functional evaluation of the Scandinavian Total Ankle Replacement. 2004 Jun The purpose of this study was to evaluate the function of the ankle joint during walking before and after Scandinavian Total Ankle Replacement (STAR). Nine patients (six males and three females) with an average age of 65 years, scheduled for unilateral total ankle replacement for osteoarthritis and rheumatoid arthritis, were evaluated both preoperatively and postoperatively in a gait analysis laboratory. Arthroplasty patients showed reduced range of motion at the ankle compared to normal controls. Postoperative arthroplasty subjects had significantly improved external ankle dorsiflexion moment, the moment that affects the plantarflexor muscles, when compared to their preoperative status. The moment in arthroplasty patients was increased, indicating improved function of the ankle joint.
12952049 Arthritis and related diseases of the foot and ankle: rehabilitation and biomechanical con 2003 Jul Arthritis and other rheumatic conditions are among the most common disabilities in the United States. Although arthritic conditions affect the knee and hip joints more frequently than the joints of the foot, disorders of the foot are particularly disabling. This article outlines the types of arthritis conditions affecting the foot and discusses strategies for management and rehabilitation.
15246027 Is rheumatoid arthritis premature osteoarthritis with fetal-like healing? 2004 Jun Rheumatoid arthritis is now known to share many pathogenetic features with osteoarthritis including synovial activation with release of pro-inflammatory cytokines into the synovial fluid. As premature chondrocyte aging and dedifferentiation is increasingly accepted as integral to OA pathogenesis, premature aging of chondrocytes and perhaps subchondral bone may underlie RA. This hypothesis explains many otherwise enigmatic features of RA joint pathology such as the homing of pannus to cartilage. In addition, the surprising finding of mesenchymal precursor cells in RA joints has led to speculation that some aspect of RA pathogenesis involves an attempt to recapitulate the embryonic limb development program. In its totality, RA seems to consist of an attempt to regenerate damaged cartilage and subchondral bone in an adult organism. Since this is impossible, the best the pannus can do is to crawl through empty cartilage lacunae and replace the cartilage and subchondral bone with scar tissue. As opposed to fetal healing, inflammation is necessary to sustain and control the fibroproliferation. Two recently-discovered blood cell types seem to maintain and regulate fibroplastic states in humans: (1) CD34+ and/or monocytoid stem-cell precursors replace aging mesenchymal cells, and (2) regulatory-type adherent CD4+CD28-T cells control growth of those increasingly apoptosis-resistant mesenchymal cells. Such cells occur at multiple sites in AID patients.