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ID PMID Title PublicationDate abstract
10678064 [Total knee replacement in diabetic patients]. 1997 Aug From December 1987 to March 1995, 16 TKRs were performed for 9 diabetic patients at our department. 7 of them had rheumatoid arthritis (RA), and 2 osteoarthritis (OA). There were 1 male and 8 females. The average age was 55.9 years (range 49-69 years), and the average weight was 64.5 kg (range 54-78 kg). According to the hospital for special surgery (HSS) knee rating scale, the pre and postoperative evaluations were made. The HSS scores were improved after the operation from average 30.2 points preoperatively to 78.2 points postoperatively. The excellent and good rate was 94%. After 3.9 years follow-up (range 10 months to 8 years), the HSS score was 74.4 points, and the rate of excellent and good was 87.5%. Compared to the other 209 RA or OA patients with 287 TKR at the same period, the HSS score was almost the same, but the infection rate was higher (3.5%). We conclude that the TKR of diabetic patients could also get the similar results as common patients if the patients are under the good control of glycemia and medical treatment.
9375867 Comparison of 3 quantitative measures of hand radiographs in patients with rheumatoid arth 1997 Nov OBJECTIVE: To compare 3 quantitative hand radiograph scores, Steinbrocker stage, Larsen score, and Sharp score modified by Kaye, to one another and to other measures of clinical status in a cross sectional analysis of hand radiographs of 173 patients with rheumatoid arthritis (RA). METHODS: Radiographs were scored and compared to other measures of clinical status according to correlation and cross tabulation analyses. RESULTS: In these cross sectional studies, radiographic scores according to all 3 methods were correlated at high levels (r(s) > 0.5) with one another and duration of disease, as well as with scores for physical joint deformity and limited motion; at lower levels (0.3 < r(s) < 0.5) with physical joint swelling scores, functional status, and age; and at low levels of marginal or no clinical importance (r(s) < 0.3) with physical joint tenderness scores, laboratory data, and pain scores. CONCLUSION: The 3 scoring methods give similar quantitative information concerning hand radiographs of patients with RA. The Larsen and modified Sharp scores are preferred measures, as the detailed information facilitates comparison of different patients and monitoring of individual patients over time.
9818648 Effect of low dose methotrexate on markers of bone metabolism in patients with rheumatoid 1998 Nov OBJECTIVE: To evaluate markers of bone metabolism in patients with active rheumatoid arthritis (RA) and the effect of weekly low dose methotrexate (MTX) on bone turnover. METHODS: Forty-two menstruating female patients recently diagnosed to have RA (mean age 35.4 years, mean disease duration 1.03 years) were enrolled in this study. Disease activity was assessed by Ritchie articular index, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); laboratory tests were done for deoxypyridinoline and bone alkaline phosphatase. Drug therapy was started in the form of a weekly MTX dose (range 10-15 mg). Patients were reassessed after 3 and 9 months for the same variables. No patient received steroids before or during the course of the study. RESULTS: Thirty patients continued the study until 9 months. The mean value for deoxypyridinoline and bone alkaline phosphatase on entry were 8.4 and 12.5; mean values of Ritchie articular index and ESR were initially 10.1 and 59 mm, respectively. In patients with active RA deoxypyridinoline was significantly high (p < 0.01), while bone alkaline phosphatase was negatively correlated (p < 0.01). At 3 months deoxypyridinoline levels had fallen to 6.2, while bone alkaline phosphatase had risen to 18.8. At 9 months there was significantly reduced deoxypyridinoline, to 5.5 (p < 0.001), while bone alkaline phosphatase had risen significantly to 30 (p < 0.001) compared with pre-MTX assessment. CONCLUSION: In patients with RA bone metabolism is affected. In active disease, there was decreased bone formation, while bone resorption was increased. The therapy of weekly low dose MTX had improved bone resorption, suggesting that in patients with RA MTX might have a bone protective effect by controlling disease activity.
10666174 A prospective study on the incidence of rheumatoid arthritis among people with persistent 2000 Feb OBJECTIVES: To study the stability of rheumatoid factor (RF) increases and to compare the incidence of rheumatoid arthritis (RA) in people with transient or persistent increase of one or more RF isotypes. METHODS: From an original cohort of nearly 14 000 participants in a population study, 135 previously RF positive persons were recruited in 1996 and evaluated according to the 1987 ACR criteria. The observation time ranged from 9-22 years (mean 16. 5). Blood samples were obtained from all participants at entry and again in 1996. RESULTS: About 40% of the participants who had only one raised RF isotype in the original sample had become RF negative in 1996 compared with only 15% of those with increase of two or three RF isotypes (p=0.002). The seven participants who developed RA during the study period all had persistently raised RF. Six of the 54 participants with more than one RF isotype raised in 1996 developed RA, corresponding to an annual incidence of 0.67%, which was 7.5 times higher than observed in the other participants (p=0. 045). CONCLUSION: Symptom free persons with persistently raised RF have greatly increased risk of developing RA. This suggests that dysregulation of RF production is a predisposing factor in RA.
11438045 Approaches to enhancing the retroviral transduction of human synoviocytes. 2001 This report concerns a clinical trial for rheumatoid arthritis (RA), approved by the US National Institutes of Health and the Food and Drug Administration. An amphotropic retrovirus (MFG-IRAP) was used ex vivo to transfer a cDNA encoding human interleukin-1 receptor antagonist (IL-1Ra) to synovium. The protocol required the transduced cells to secrete at least 30 ng IL-1Ra/10(6) cells per 48 h before reimplantation. Here we have evaluated various protocols for their efficiency in transducing cultures of human rheumatoid synoviocytes. The most reliably efficient methods used high titer retrovirus (approximately 10(8) infectious particles/ml). Transduction efficiency was increased further by exposing the cells to virus under flow-through conditions. The use of dioctadecylamidoglycylspermine (DOGS) as a polycation instead of Polybrene (hexadimethrine bromide) provided an additional small increment in efficiency. Under normal conditions of static transduction, standard titer, clinical grade retrovirus (approximately 5 x 10(5) infectious particles/ml) failed to achieve the expression levels required by the clinical trial. However, the shortfall could be remedied by increasing the time of transduction under static conditions, transducing under flow-through conditions, or transducing during centrifugation.
11295469 Identification of four novel dinucleotide repeat polymorphisms in the IL-2 and IL-2beta re 2001 Apr Two polymorphic regions have been described within the IL-2 and IL-2 receptor beta genes comprising 15 and 8 alleles, respectively. Whether these polymorphisms have biologic importance is unknown, although they have been variably identified in associated with certain chronic disease states. We report here the detection of four new alleles designated IL-2 A* (122 bp), IL-2R-2 (169 bp), IL-2R 0 (165 bp), and IL-2R 9 (147 bp) in patients with rheumatoid arthritis and normal controls from the Pacific Northwest. The number of alleles now recognized at these loci within the IL-2 and IL-2Rbeta genes increases to 16 and 12, respectively.
10629873 [Effects of orally available prodrug of cromoglycic acid on collagen-induced arthritis mic 1999 Oct Cromoglicate lisetil (CL) is an orally deliverable prodrug of cromoglycic acid, having diethyl promoieties and a lysyl promoiety for its optimum drug-delivery. We examined the effects of CL on bovine type II collagen (CII)-induced arthritis (CIA) of male DBA/1J mice, an experimental model for human rheumatoid arthritis, and its action mechanism. CL (100 mg/kg/day) was given by gavage to CII-immunized mice once daily for 6 weeks, starting when arthritic symptoms became evident. Symptomatic scores of arthritis obviously elevated in non-treated CIA mice at week 6.5 after initial immunization and continued elevated thereafter throughout the experiment, the elevation which was reduced by CL. CL also improved radiographic score of phalangeal destruction and pathohistological indexes at the end of treatment period. Serum anti-CII antibody titer was increased in non-treated CIA mice and the elevation was reduced by CL treatment. Mast cells (MCs) number in arthritic region was increased in non-treated CIA mice but not by CL treatment. In conclusion, oral CL treatment proved beneficial in CIA mice. Observed correlation between the CL effect on CIA and that on MCs number suggests the potential contribution of MCs to accelerate chronic arthritic processes and may further implicate potential action mechanism of CL, which may act by regulating MC functions for chronic inflammation.
10990219 HLA-DRB1 genes, rheumatoid factor, and elevated C-reactive protein: independent risk facto 2000 Sep OBJECTIVE: To evaluate the prognostic value of HLA-DRB1 antigens, rheumatoid factor (RF), and C-reactive protein (CRP) with the radiographic outcome of rheumatoid arthritis (RA). METHODS: In total, 139 patients with early RA (< 2 years) were followed up. At the end of 3 year treatment with disease modifying antirheumatic drugs (DMARD) HLA genotyping and external radiographic scoring were performed. The time up to the first development of erosive disease [Ratingen radiographic score (RS) > 0, > 5, > 10] was compared by methods of survival analysis. RESULTS: At 4 years' disease duration, DRB1*04 or DRB1*01 positive patients had RS > 0 or > 10 (73% and 27%, respectively) significantly more frequently than DRB1*04 or DRB1*01 negative patients (37% and 7%, respectively). Nearly independently of the genetic predisposition, RF and elevated CRP at the start of DMARD treatment were predictive for erosive RA at 4 years. Elevated CRP (> or = 15 mg/l) increased the probability of erosive RA in DRB1*04 or DRB1*01 positive patients from 64.0% (in patients with CRP < 15 mg/l) to 83.9%, and in DRB1*04 and DRB1*01 negative patients from 18.8% to 70.1%. The corresponding figures for RF+ and RF- patients were 58.2% and 82.5% in HLA predisposed patients and 23.5% and 60.2% in those who were negative for DRB1*04 and DRB1*01. The probability of a RS > 10 was 40.9% for HLA predisposed patients with elevated CRP. In contrast, no case with RS > 10 was found in 43 patients who had neither of these 2 risk factors. CONCLUSION: Our findings support that HLA predisposition plays an important role with regard to radiographic progression. However, this effect is modified by RF serum concentration and disease activity.
11093598 Cervical spine surgery in rheumatoid arthritis. A Swedish nation-wide registration of 83 p 2000 OBJECTIVE: To investigate diagnostic methods, surgical methods and indications, early complications and short term outcome of cervical spine surgery for rheumatoid arthritis (RA). METHODS: A nation-wide registration of rheumatoid cervical spine surgery carried out in Sweden during 1993. RESULTS: Eighty-six (74 primary) procedures in 83 patients were reported from 11 hospitals. Pain was a more common indication for surgery than was neurologic impairment. C1-C2 instability or subluxation was present in 66/82, subaxial subluxations in 27/82 and atlantoaxial impaction in 10/82 procedures (data partly missing in one case). Indications for surgery and preoperative investigations were found to be reasonably uniform, but surgical methods and post-operative care varied between hospitals. Posterior fusion was performed in 76 patients. C1-C2 wiring with bone grafting was the most common procedure followed by occipito-cervical fusion with wires and bone cement. Subaxial cervical decompression without fusion, posterior fusion with onlay graft only, and carbon fiber grafts were used in a small number of patients. Total mortality was 5/83. The early complication rate was low, but 17 patients showed recurrent subluxation at follow-up at median 7 (1-17) months. Seven of them required reoperation in the same segment. CONCLUSION: The variation in treatment policy and number of operated patients in the different hospitals speak in favor for centralization of cervical spine surgery in RA. New methods for C1-C2-fusion need to be evaluated.
9833251 Urinary neopterin excretion and dihydropteridine reductase activity in rheumatoid arthriti 1998 Neopterin and biopterin are two products of the pteridine pathway. Even though their roles and interrelationships have not been exactly clarified, neopterin is known as a biomarker of cell-mediated immunity. In this case, the highly elevated neopterin levels are parallel to the slightly elevated biopterin levels. On the other hand, the reduced form of biopterin-tetrahydrobiopterin is an essential cofactor of aromatic monoxygenases that leads to synthesis of tyrosine, tryptophan and dopamine neurotransmitters and its concentration in body fluids and tissues is maintained by the enzyme dihydropteridine reductase (DHPR). Increased numbers of activated lymphocytes can be found in peripheral blood, in the synovial fluid and synovial membranes or patients with rheumatoid arthritis (RA). Since the present study was undertaken to evaluate the role of the pteridine pathway in RA, we measured urine neopterin levels and dried blood DHPR activities in 36 patients with RA and in 20 healthy volunteers, in parallel with other clinical parameters. We found that neopterin excretion was significantly increased in RA patients compared with controls. The means were 433 +/- 216, 153 +/- 43 and 111 +/- 34 mumol/mol creatinine for patients in active stage, in remission and controls, respectively. Our results suggest that urine neopterin levels were strongly dependent on the stage and activity of RA. Either as an effect of the disease itself or of drug administration, slightly reduced DHPR activities were detected (3.484 +/- 0.304 for control, 2.974 +/- 0.255 in active stage RA, and 3.048 +/- 0.302 red cytochrome C/min/5 mm disc in remission).
10380256 Relationship of rheumatoid factor isotype levels with joint lesions detected by magnetic r 1999 May OBJECTIVE: To evaluate the relationship between rheumatoid factor isotypes and articular damage detected by magnetic resonance imaging and plain radiography in early rheumatoid arthritis. METHODS: 20 consecutive patients with early active rheumatoid arthritis underwent determinations of serum IgM, IgA, and IgG rheumatoid factors by enzyme-linked immunosorbent assay (ELISA). Plain radiographs of the hands and wrists were obtained, and the wrist, metacarpophalangeal joints, and proximal interphalangeal (PIP) joints on the more severely affected side were investigated by magnetic resonance imaging before and after gadolinium-DTPA injection. RESULTS: IgM, IgA, and IgG rheumatoid factors were found in 13 (65%), 13 (65%), and 15 (75%) of patients, respectively. Sera from five patients (25%) contained no detectable rheumatoid factor isotypes. Correlations were found among the levels of the three rheumatoid factor isotypes. Levels of IgA, IgG, and IgM rheumatoid factor were significantly higher in patients with than without erosions on magnetic resonance imaging scans. No such difference was found when patients with and without erosions on plain radiographs were compared. Magnetic resonance imaging detected soft tissue lesions more frequently than plain radiography. Magnetic resonance imaging was also more likely than plain radiography to show bone erosions and bone cysts, but this difference was not statistically significant. CONCLUSIONS: Quantitative rheumatoid factor isotype assays and magnetic resonance imaging evaluation of erosions of the hand and wrist may be useful for investigating patients with early rheumatoid arthritis.
10425897 [Virkersund Spa. Changes in patient admission and therapeutic outcome over the last 15 yea 1999 Jun 30 Since the spa resort Vikersund Kurbad was reorganised in 1992 as a retraining unit, improvements have taken place. There is now one fulltime rheumatologist, two part-time general practitioners, 14 physiotherapists, one social worker and nurses in a new unit with a hot pool and an occupational therapy department. In this article, assessment data continuously recorded since 1981 are used to find out how the changes have affected patient intake and patient improvement. It was found that the patients now admitted are more disabled, but the number of patients who thrive and improve has increased. However, the intake of rheumatic patients has simultaneously decreased. It is suggested that measures are taken to enable more rheumatics to use the institution.
10555024 Evaluation of pannus and vascularization of the metacarpophalangeal and proximal interphal 1999 Nov OBJECTIVE: To evaluate the extent of intraarticular vascularization and pannus formation in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of patients with rheumatoid arthritis (RA) by high-resolution ultrasound (US). METHODS: A newly developed, high-resolution multidimensional linear array US was utilized to obtain longitudinal and transverse scans of joints with active RA (n = 21), moderately active RA (n = 39), or inactive RA (n = 93), and of joints from healthy controls (n = 120). RESULTS: Healthy joints had no detectable pannus, whereas pannus could be detected in 52% of the joints with active RA, 82% of the joints with moderately active RA, and 67% of the joints with inactive RA. There was a significant difference in vascularization in the joints of all subgroups of RA patients and those of healthy subjects (P < 0.001). Moreover, vascularization differed significantly among the RA subgroups: inactive versus moderately active RA (P < 0.02) and inactive versus active RA (P < 0.05). Both pannus and vascularization appeared to be localized preferentially on the radial side of the joints. CONCLUSION: Evaluation of pannus and the extent of vascularization within the joints of patients with RA by high-resolution US might be helpful in the assessment of disease activity, and thus influence therapeutic strategies.
9771209 Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals a high preva 1998 Jun OBJECTIVES: To evaluate the role of magnetic resonance imaging (MRI) of the wrist in detecting early joint damage in patients with rheumatoid arthritis (RA). METHODS: MRI was performed on 42 patients with early RA (median symptom duration of four months). Scans were scored separately by two musculoskeletal radiologists using a newly devised scoring system, which was validated. MRI findings were compared with plain radiography, clinical measures, and HLA-DRB*01/04 genotyping. RESULTS: Interobserver reliability for the overall MRI score was high (r = 0.81) as was intraobserver reliability (r = 0.94 for observer 1 and 0.81 for observer 2). There was more variation in scoring synovitis (interobserver reliability: r = 0.74). Erosions were detected in 45% of scans (19 of 42), compared with 15% of plain radiographs. The most common site for erosions was the capitate (39%), for synovitis the ulnar aspect of the radiocarpal joint, and for tendonitis, the extensor carpi ulnaris tendon. The total MRI score and MRI synovitis score correlated most significantly with C reactive protein (r = 0.40 and 0.42 respectively, p < 0.01). The MRI erosion score was highly correlated with MRI bone marrow oedema (r = 0.83) as well as the Ritchie score and disease activity score (r = 0.32, p < 0.05). HLA-DRB1*04 or *01 (shared epitope +ve) was found in 76% of patients; 84% of those with MRI erosions and 69% of those without (NS, p = 0.3). CONCLUSIONS: A high proportion of RA patients develop MRI erosions very early in their disease, when plain radiography is frequently normal. MRI of the dominant wrist may identify those requiring early aggressive treatment.
10556259 Serum levels of matrix metalloproteinase-3 in relation to the development of radiological 1999 Nov OBJECTIVE: To evaluate the significance of serum matrix metalloproteinase-3 (MMP-3) levels in relation to the development of radiological damage (X-ray damage) in early rheumatoid arthritis (RA). METHODS: Serum MMP-3 levels were measured in 46 healthy controls (CTRL), 19 osteoarthritis (OA) and 78 RA patients with joint symptoms for <1 yr at presentation (T0): 48 patients without and 30 with X-ray damage at T0. Serum MMP-3, measured by ELISA, and X-ray damage, scored according to Sharp's method, were assessed at 0, 6, 12 and 24 months. RESULTS: MMP-3 levels in CTRL and OA were low or undetectable with no differences between the groups (P=0.19). Levels in RA were higher than in CTRL (P<0.01). Initial MMP-3 levels in patients with X-ray damage at T0 (n=30) were higher than the levels in patients without any X-ray damage during follow-up (n=19) (P<0.01), but were not different from those in patients who developed X-ray damage during the study (n=29) (P=0.11). In the patients without X-ray damage at T0, there was a significant correlation between MMP-3 at T0 and the total X-ray damage after 6 months (r=0.34, P=0.02) and 12 months (r=0.32, P=0.03). This correlation was almost exclusively determined by joint space narrowing in the Sharp score. CONCLUSION: The serum MMP-3 level seems to be an indicator for the development of radiological damage in patients with early RA and appears to be particularly indicative of cartilage degradation.
9844762 Cyclosporine A in the treatment of early rheumatoid arthritis. A prospective, randomized 2 1998 Nov OBJECTIVE: To investigate the efficacy, tolerability and safety of cyclosporine A (CSA) in early rheumatoid arthritis (RA) patients. METHODS: Patients with an early diagnosis of RA, a disease duration of less than 3 years, and without prior disease modifying antirheumatic drug (DMARD) treatment were studied. They randomly received oral CSA (3 mg/kg/day) or oral methotrexate (MTX) (0.15 mg/kg/week). In addition, all patients in both groups received oral prednisone (7.5 mg/day). RESULTS: Fifty-two patients were assigned to the CSA group and 51 to the MTX group. After 24 months of treatment, 48 patients from the CSA group and 48 from the MTX group showed significant clinical improvement. This was evaluated by the duration of morning stiffness, grip strength, the total joint count, joint swelling, and joint tenderness and pain, compared to pre-treatment values. The clinical improvement was also associated with a significant decrease in ESR and CRP values in both groups. No significant radiological deterioration was observed in the CSA patients compared to those treated with MTX after 24 months. Four patients from the CSA group dropped out of the study, two because of a synovitis flare, one because of severe hypertrichosis and one because of severe gingival hyperplasia. Three patients from the MTX group withdrew, one because of disease flare-up and two because of gastrointestinal disturbances. CONCLUSION: Early immunointervention in RA patients appears to be crucial to limit the development of joint damage. Cyclosporine A appears to be effective, well tolerated and safe in the long-term treatment of RA and can therefore be used as a first immunomodulatory drug in the armamentarium for the treatment of RA.
9225595 The association between arthritis and the weather. 1997 Jun Despite the prevasiveness of the idea that arthritis is influenced by the weather, scientific evidence on the matter is sparse and non-conclusive. This study, conducted in the Australian inland city of Bendigo, sought to establish a possible relationship between the pain and rigidity of arthritis and the weather variables of temperature, relative humidity, barometric pressure, wind speed and precipitation. Pain and rigidity levels were scored by 25 participants with osteoarthritis and/or rheumatoid arthritis four times per day for 1 month from each season. Mean pain and rigidity scores for each time of each day were found to be correlated with the meteorological data. Correlations between mean symptoms and temperature and relative humidity were significant (P < 0.001). Time of day was included in the analysis. Stepwise multiple regression analysis indicated that meteorological variables and time of day accounted for 38% of the variance in mean pain and 20% of the variance in mean rigidity when data of all months were considered. A post-study telephone questionnaire indicated 92% of participants perceived their symptoms to be influenced by the weather, while 48% claimed to be able to predict the weather according to their symptoms. Hence, the results suggest (1) decreased temperature is associated with both increased pain and increased rigidity and (2) increased relative humidity is associated with increased pain and rigidity in arthritis sufferers.
10468415 Chronic tophaceous gouty arthritis mimicking rheumatoid arthritis. 1999 Aug OBJECTIVES: To analyze the factors which differentiate chronic tophaceous arthritis from rheumatoid arthritis. METHODS: We describe two cases of chronic gouty arthritis masquerading as rheumatoid arthritis. The characteristic features of each of these two conditions and the diagnostic approach are discussed in light of relevant literature. RESULTS: The correct diagnosis was reached by the combination of accurate history taking (family history of gout, alcoholism, previous diuretic therapy and renal stones), guiding clinical features (subcutaneous tophaceous deposits) and specific radiological (assymetrical erosions with sclerotic margins and overlying edges) and laboratory findings (hyperuricemia and hyperuricosuria). It was confirmed by the identification of monosodium urate (MSU) crystals in the synovial and subcutaneous tissues. CONCLUSIONS: Gout and rheumatoid arthritis rarely coexist. Chronic gouty arthritis may mimic rheumatoid arthritis, and vice-versa. Clinical suspicion supplemented by characteristic laboratory, radiological and histologic findings help at reaching an accurate diagnosis.
11094923 Implications of depression in rheumatoid arthritis: do subtypes really matter? 2000 Feb OBJECTIVE: To examine depressive disorders and health status in patients with rheumatoid arthritis (RA), controlling for potential confounds. METHOD: Subjects (n = 426) completed measures of depressive symptoms (Center for Epidemiological Studies Depression Scale [CES-D]) and health status (Arthritis Impact Measurement Scales 2 [AIMS2]), via cross-sectional survey. Subjects (n = 299) with few depressive symptoms (CES-D < or = 10) were not evaluated further. Subjects with CES-D > or = 11 were interviewed using the Primary Care Evaluation of Mental Disorders to diagnose major depressive disorder (MDD; n = 46), dysthymic disorder (DD; n = 21), or minor depressive disorder (MND; n = 18). RESULTS: Regression analyses examined differences between the depressive disorders on AIMS2 subscales. Health status scores were similar between the depressive disorder subcategories; significant differences were found between MDD and MND on AIMS2 Physical scores and MDD and DD on AIMS2 Symptom scores. CONCLUSION: Regarding health status, presence of depression itself seems to overshadow differences between depression subtypes; antidepressant treatments/referrals for persons with concomitant RA and any depressive disorder subtype appear warranted.
11142719 Apoptosis as a target for gene therapy in rheumatoid arthritis. 2000 Rheumatoid arthritis (RA) is characterized by chronic inflammation of the synovial joints resulting from hyperplasia of synovial fibroblasts and infiltration of lymphocytes, macrophages and plasma cells, all of which manifest signs of activation. All these cells proliferate abnormally, invade bone and cartilage, produce an elevated amount of pro-inflammatory cytokines, metalloproteinases and trigger osteoclast formation and activation. Some of the pathophysiological consequences of the disease may be explained by the inadequate apoptosis, which may promote the survival of autoreactive T cells, macrophages or synovial fibroblasts. Although RA does not result from single genetic mutations, elucidation of the molecular mechanisms implicated in joint destruction has revealed novel targets for gene therapy. Gene transfer strategies include inhibition of pro-inflammatory cytokines, blockade of cartilage-degrading metalloproteinases, inhibition of synovial cell activation and manipulation of the Th1-Th2 cytokine balance. Recent findings have iluminated the idea that induction of apoptosis in the rheumatoid joint can be also used to gain therapeutic advantage in the disease. In the present review we will discuss different strategies used for gene transfer in RA and chronic inflammation. Particularly, we will high-light the importance of programmed cell death as a novel target for gene therapy using endogenous biological mediators, such as galectin-1, a beta-galactoside-binding protein that induces apoptosis of activated T cells and immature thymocytes.