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ID PMID Title PublicationDate abstract
16470008 Evidence for genetic variation as a factor in maintaining health. 2006 Feb For many chronic diseases, the influence of genetics is subtle and complex and does not conform to simple Mendelian patterns of inheritance as is seen with single-gene disorders. Genetic variation can influence the propensity for the initiating event, the progression to a clinical disease state, and the trajectory of disease. One example of how genetic variations may affect complex diseases is provided by the interleukin 1 family of cytokines. This cytokine family plays a key role in mediating inflammation, which is a central component of many chronic diseases, including coronary artery disease and rheumatoid arthritis. Recent research has identified many sequence variations in the regulatory DNA of the genes coding for important members of the interleukin 1 family, and these variations are associated with differential effects on the inflammatory response. These in turn alter the risk of some diseases in which inflammation plays a role and also affect physiologic responses, such as the inflammatory response to exercise. As this new genetic knowledge is developed and extended, it may be possible to make health care interventions at an earlier stage, before clinical disease is established, rather than after tissues have been permanently damaged.
18176989 Rituximab therapy in rheumatoid arthritis in daily practice. 2008 Jan OBJECTIVE: Rituximab has been shown to be effective in refractory rheumatoid arthritis (RA) in randomized controlled trials, allowing approval by health agencies. Our aim was to assess in routine care the effects of rituximab in patients with RA who had experienced an inadequate response to anti-tumor necrosis factor-alpha (TNF-alpha) agents or had a contraindication to these drugs. METHODS: An observational retrospective study was conducted. Rituximab (1000 mg intravenous infusion on Days 1 and 15) was administered with concomitant methotrexate therapy. Responses defined according to the European League Against Rheumatism (EULAR criteria) were assessed at Week 24. RESULTS: Fifty patients were included: 30 had inadequate response to anti-TNF-alpha and 20 had contraindication to anti-TNF-a drugs. EULAR response was observed in 82%, good response in 36% (including remission in 12%), moderate response in 46%, and no response in 18%. One infusion-related reaction and 2 pulmonary infections occurred. Eleven of the 50 patients (22%) experienced flare and received retreatment with rituximab at 6 months. Thirty additional patients had flare after 6 months and the median delay for retreatment among the 41 responders was 9 (range 6 24) months. No difference regarding efficacy or tolerance of rituximab was observed according to previous inadequate response or contraindication to anti-TNF. CONCLUSION: A single cycle of rituximab, in combination with continued methotrexate, provided significant improvement in disease activity at Week 24, with good tolerance, in patients with severe and active RA despite anti-TNF-alpha agents and/or with contraindication to these drugs, in this daily practice study.
18953542 Impact of sex, age, body mass index and handedness on finger joint space width in patients 2009 Mar To evaluate the associations between sex, age, body mass index (BMI) and handedness regarding the radiogeometric detectable joint space distances of the finger articulations in patients suffering from a prolonged course of rheumatoid arthritis (RA). The joint space widths were measured by a new available Computer-aided joint space analysis (CAJSA); 128 patients with RA underwent computerized semi-automated joint space analysis of joint space distances at the metacarpal-phalangeal articulation (JSD-MCP II-V), proximal-interphalangeal joint (JSD-PIP II-V) and distal-interphalangeal joint (JSD-DIP II-V) based on digitally performed radiographs of the hand (Radiogrammetry Kit, Version 1.3.6; Sectra; Sweden). The joint space distance (JSD) of each articulation was expressed as JSD total in millimeter. The patient cohort was differentiated for gender, age, handedness and BMI (BMI < 20; BMI 20-25, BMI > 25). JSD revealed a significant age-related narrowing of 24.8% (JSD-MCP), 22.6% (JSD-PIP) and 28.7% (JSD-DIP) between the ages of 20 and 79. Additionally, males showed a significantly wider JSD compared to the female cohort for all age groups. All JSD-distances were varied between the right and left hand. The JSD-MCP demonstrated significant differences regarding the BMI groups. In contrast to JSD-MCP an effect of the BMI on measurements of JSD-PIP and JSD-DIP could not be observed. These influences must be differentiated from disease-related alterations caused by RA.
18434448 Genetic variation in the nuclear factor kappaB pathway in relation to susceptibility to rh 2009 Apr OBJECTIVE: To examine genetic association between rheumatoid arthritis (RA) and known polymorphisms in core genes of the nuclear factor (NF)kappaB pathway, the major intracellular pathway in RA pathogenesis. METHODS: Discovery and replication sample sets of Spanish patients with RA and controls were studied. A total of 181 single nucleotide polymorphisms (SNPs) uniformly spaced along the genomic sequences of 17 core genes of the NFkappaB pathway (REL, RELA, RELB, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, IKBKA, IKBKB, IKBKE, IKBKAP, KBRAS1, KBRAS2, MAP3K1, MAP3K14, TAX1BP1) were studied by mass spectrometry analysis complemented with 5'-nuclease fluorescence assays in the discovery set, 458 patients with RA and 657 controls. SNPs showing nominal significant differences were further investigated in the replication set of 1189 patients with RA and 1092 controls. RESULTS: No clear reproducible association was found, although 12 SNPs in IKBKB, IKBKE and REL genes showed significant association in the discovery set. Interestingly, two of the SNPs in the IKBKE gene, weakly associated in the discovery phase, showed a trend to significant association in the replication phase. Pooling both sample sets together, the association with these two SNPs was significant. CONCLUSION: We did not find any major effect among the explored members of the NFkappaB pathway in RA susceptibility. However, it is possible that variation in the IKBKE gene could have a small effect that requires replication in additional studies.
17661906 The PTPN22 promoter polymorphism -1123G>C association cannot be distinguished from the 185 2007 Sep The protein tyrosine phosphatase nonreceptor 22 (PTPN22) gene has, during the last 2 years, been recognized as a susceptibility gene for numerous autoimmune diseases, including rheumatoid arthritis (RA) and type 1 diabetes. An association between the exonic 1858C>T single nucleotide polymorphism (SNP) and RA has repeatedly been replicated in several Caucasian populations. The SNP is not associated with autoimmune diseases in Asian populations, as the 1858T allele is almost absent. Recently, a promoter polymorphism -1123G>C was proposed to be associated with acute-onset type 1 diabetes in Japanese and Korean populations. Furthermore, in Caucasian populations, the presence of additional PTPN22 risk variants has been suggested, indicating that the 1858C>T risk variant cannot explain the entire disease association observed in the region. In this study, we wanted to jointly address and integrate these separate findings to further elucidate the association between the PTPN22 gene and RA in a Norwegian material of 861 RA patients and 559 healthy controls. Our results revealed that the strength of the association with the PTPN22 promoter polymorphism, -1123G>C, is analogous to that observed for 1858C>T. As the -1123G>C variant is also polymorphic in Asian populations, our data underpin the need to further explore the association between this variant and autoimmune diseases in different populations.
18710899 Acupuncture for rheumatoid arthritis: a systematic review. 2008 Dec The aim of this systematic review is to evaluate the available evidence, from randomized clinical trials (RCTs), of acupuncture for treating patients with RA. Systematic searches were conducted on 17 databases up to April 2008 without the language restriction. All RCTs of acupuncture, with or without electrical stimulation or moxibustion, for patients with RA were considered for inclusion. A total of 236 potentially relevant studies were identified and eight RCTs were included. Four RCTs compared the effects of manual or electro-acupuncture with penetrating or non-penetrating sham acupuncture and failed to show specific effects of acupuncture on pain [n = 88; weighted mean differences (WMD), 10 cm VAS -0.46; 95% CI -1.70, 0.77; P = 0.46; heterogeneity: tau(2) = 0.19; chi(2) = 2.38; P = 0.30; I (2) = 16%] or other outcome measures. One RCT compared manual acupuncture with indomethacin and suggested favourable effects of acupuncture in terms of total response rate. Three RCTs tested acupuncture combined with moxibustion, vs conventional drugs and failed to show that acupuncture plus moxibustion was superior to conventional drugs in terms of response rate (n = 345; RR 1.12; 95% CI 0.99, 1.28; P = 0.08; heterogeneity: tau(2) = 0.00; chi(2) = 1.34; P = 0.51; I(2) = 0%), pain reduction (n = 105; WMD, 10 cm VAS 1.53; 95% CI -0.57, 3.63; P = 0.15; heterogeneity: tau(2) = 1.18; chi(2) = 1.81; P = 0.18; I(2) = 45%) or joint swelling index (n = 105; WMD, 10 cm VAS 0.25; 95% CI -1.31, 1.82; P = 0.75; heterogeneity: tau(2) = 0.18;chi(2) = 1.14; P = 0.28; I(2) = 13%). In conclusion, penetrating or non-penetrating sham-controlled RCTs failed to show specific effects of acupuncture for pain control in patients with RA. More rigorous research seems to be warranted.
18982072 Intra-articular fms-like tyrosine kinase 3 ligand expression is a driving force in inducti 2008 BACKGROUND: One of the hallmarks of rheumatoid arthritis (RA) is hyperplasia and inflammation of the synovial tissue being characterized by in situ occurrence of highly differentiated leukocytes. Fms-like tyrosine kinase 3 (Flt3) has a crucial role in hematopoiesis, regulation of cell proliferation, differentiation and apoptosis. Typically, Flt3 is expressed on early myeloid and lymphoid progenitors and is activated by its soluble ligand (Flt3-L). The highly differentiated cellular pattern in the synovium of the RA patients made us hypothesize that Flt3-L, with its ability to induce proliferation and differentiation, could be of importance in induction and/or progression of arthritis. METHODOLOGY/PRINCIPAL FINDINGS: To investigate occurrence of Flt3-L in RA we have measured its levels in matched serum and synovial fluid samples from 130 patients and 107 controls. To analyse the pro-inflammatory role of Flt3-L, we continuously overexpressed this protein locally in healthy mouse joints using homologous B-cell line transfected with Flt3-L gene. Additionally, recombinant Flt3-L was instillated intra-articularly in combination with peptidoglycans, a Toll Like Receptor 2-ligand with stong arthritogenic properties. Our results show significantly higher levels of Flt3-L in the synovial fluid as compared to serum levels in RA subjects (p = 0.0001). In addition, RA synovial fluid levels of Flt-3-L were significantly higher than these obtained from synovial fluids originating from non-inflammatory joint diseases (p = 0.022). Intra-articular administration of B-cell line transfected with Flt3-L gene resulted in highly erosive arthritis while inoculation of the same B-cell line without hyperexpression of Flt3-L did not induce erosivity and only in a minority of cases caused synovial proliferation! Flt3-ligand potentiated peptidoglycan induced arthritis as compared to mice injected with peptidoglycan alone (p<0.05). CONCLUSIONS/SIGNIFICANCE: Our findings indicate that Flt3-L is strongly expressed at the site of inflammation in human RA. It exerts both pro-inflammatory and tissue destructive properties once in the joint cavity. Owing to these properties, treatment attempts to neutralize this molecule should be considered in RA.
16953150 Improving outcomes in tumour necrosis factor a treatment: comparison of the efficacy of th 2006 Jun AIM: The aim of this study was to evaluate the differences between infliximab and etanercept, in terms of clinical efficacy and rapidity of action. METHODS: We selected 32 patients with rheumatoid arthritis (RA) with an incomplete response to disease modifying anti-rheumatic drugs (DMARDs), and randomly assigned them to etanercept or infliximab. We evaluated the efficacy after 14, 22, 54 weeks of treatment, using the American College of Rheumatology (ACR) 20, 50 and 70 criteria, and the improvement of quality of life using the Health Assessment Question-naire (HAQ). RESULTS: After 14 weeks, the 54.4% of patients was considered ACR-responders in the etanercept group, whereas, in the infliximab group, the percentage of responders was 74.4%: infliximab gave better results for the tender joint count and for physician's global assessment. After 22 weeks, no significant difference was present. After 54 weeks, etanercept resulted more effective than infliximab for tender joint count (TJC) value, for visual analogic scale (VAS) for pain score, for global disease assessment value, with 74.4% of patients considered ACR-responders in the group treated with etanercept and 60% in the group treated with infliximab. As regards HAQ, patients in the infliximab group presented higher scores at week 14, but in weeks 22 and 54, patients in the etanercept group showed better results. Therefore, both infliximab and etanercept are efficacious in RA, but infliximab is more efficacious than etanercept in week 14. Vice versa, in week 54 etanercept is the most efficacious drug. CONCLUSIONS: Physicians have 2 weapons in their armamentarium, with the same target but distinct clinical, pharmacokinetic and pharmacodynamic properties.
18463934 Retrospective study evaluating dose standards for infliximab in patients with rheumatoid a 2008 Aug We determined, in our surrounding environment, the proportion of patients being treated with infliximab who required a therapeutic scheme escalation (an infliximab dose increase surpassing the level of 3 mg/kg every 8 weeks and/or a decrease on the current between infusions' interval). This was a study of the retrospective analysis of data from the 41 rheumatoid arthritis (RA) patients receiving an infliximab therapy at the Albert Einstein Israelita Hospital, from January 2001 up to December 2005. A questionnaire was applied to these patients, assessing their clinical and laboratory data, adverse events, and individual information regarding the infliximab administration. Therapeutic dose information was available in 68% (28/41) of the RA patients, with 46% of these (13/28) receiving a dose increase, and 30% (8/27) experiencing a shortening of the between infusions' interval. The average final infliximab dose (4.21 mg/kg) was significantly greater than their average initial dose (3.29 mg/kg). The average time intervals between the initial and final infusions, though shortened, were not significantly different. A proportion of 73% (30/41) of these patients demonstrated improvement in at least one of the assessed clinical parameters, and 50% of these patients (15/30) experienced a dose increase, while 20% (6/30) experienced shortening of the between treatments' interval. A total of 20% (8/41) of the original patients experienced adverse events. Although infliximab is effective in the control of RA, dose adjustment and/or shortening of the between treatments' interval is frequently required.
18813930 Intracellular calcium responses to cholinergic stimulation of lymphocytes from healthy don 2009 Mar This study was performed to identify the role of cholinergic stimulation on changes of intracellular calcium concentrations as intracellular messenger of neuroimmune interaction. Incubation of PBMC with acetylcholine (ACh) leads to Ca(2+) oscillations in healthy controls. PBMC from rheumatoid arthritis (RA) patients exhibited increased basal Ca(2+) concentrations with a significantly reduced capacity to respond upon ACh stimulation compared to healthy controls. It can be assumed that cholinergic signals in PBMC are mediated via the nicotinergic type of ACh receptors, causing changes in intracellular Ca(2+) concentrations with various types of oscillations. The significantly decreased modulation of intracellular Ca(2+) levels by ACh in PBMC of RA patients points further to a disturbed neuroimmune interaction in this chronic disease.
18312914 Rheumatoid forefoot reconstruction: first metatarsophalangeal joint fusion combined with W 2008 Mar This study evaluates the outcome of rheumatoid forefoot reconstruction with arthrodesis of the first metatarsophalangeal joint (MTPJ) combined with multiple Weil's metatarsal osteotomies (WMO) to the lesser rays. A retrospective study on 17 consecutive patients (26 feet) was performed with subjective, clinical, and radiological analysis. At an average follow-up of 26.2 months, patients rated the result in 88% of cases as excellent or good with 76% improvement in pain, 74% improvement in function, and 70% improvement in footwear. This corresponded with a high mean modified AOFAS score of 72/100 (34 to 90). First MTPJ arthrodesis union rate was 92%. Fourteen percent of lesser toes were aligned preoperatively compared to 86% at latest review. There was a 12% rate of recurrent metatarsalgia and or callosities. This combined procedure provides stabilization of the first ray, offloading the lesser metatarsals and preventing early recurrence of deformity. Preserving the lesser metatarsal head further widens the surgical options if revisional surgery is necessary in the future. ACFAS Level of Clinical Evidence: 4.
17849113 Sensitivity and specificity of plain radiographic features of peripheral enthesopathy at m 2007 Nov BACKGROUND: It has been proposed that the defining difference between rheumatoid arthritis and spondyloarthropathy (including psoriatic arthritis) is the initial pathological lesion where the emphasis in psoriatic arthritis is on the enthesis and in rheumatoid arthritis on the synovium. Classical radiological descriptions of seronegative spondyloarthropathy include enthesopathy at major entheseal insertions characterised by erosions and exuberant new bone formation. In this study, the plain radiographic features of spondyloarthropathy are compared between psoriatic arthritis, other spondyloarthropathies and rheumatoid arthritis. METHODS: The CASPAR study collected clinical, radiological and laboratory data on 588 patients with physician diagnosed psoriatic arthritis and 525 controls with other inflammatory arthritis, 70% of which had rheumatoid arthritis. Plain radiographs of the pelvis and heels were part of the study protocol, although radiographs of other potential entheseal sites such as the knee, elbow and shoulder, were interpreted if available. All radiographs were read blind by two observers working in tandem. RESULTS: Significant differences in entheseal erosion and entheseal new bone formation were found between psoriatic arthritis, ankylosing spondylitis, undifferentiated spondyloarthropathy, rheumatoid arthritis and other diagnoses (entheseal erosion, chi-squared 20.8, p=0.008; entheseal new bone formation, chi-squared 24.5, p=0.001). These differences were mainly due to a higher proportion of these features in ankylosing spondylitis. No differences in the plain radiographic features of enthesopathy were found between psoriatic arthritis and rheumatoid arthritis except in the case of entheseal new bone formation at sites of attachment of inguinal ligament, sartorius and rectus femoris muscles to the ilium (OR 3.01, 95% CI 1.13-8.02). Very few subjects with symptomatic heel involvement had radiographic changes and minimal differences were found between those with and without symptoms in terms of new bone formation and erosion at either calcaneal site. CONCLUSIONS: New bone formation and erosion at major entheseal sites is most commonly seen in ankylosing spondylitis. Plain radiographic features of major enthesopathy are poor discriminators between psoriatic arthritis and rheumatoid arthritis.
16343832 Iatrogenically-related, fatal methotrexate intoxication: a series of four cases. 2006 Jan 27 Since the early eighties, the folic antagonist methotrexate (MTX) has been used in long-term treatment of rheumatoid arthritis. Because of the high toxic potential clinical and laboratory controls at regular intervals and patient education in order to avoid misadventure is of overriding importance. We present four cases of fatal MTX intoxication due to medical malpractice from the Tübingen Institute of Forensic Medicine autopsy material, which show the severe consequences of MTX overdose. It becomes evident that among non-rheumatologists there still is need for information about toxicity and dose limitation in MTX low-dose treatment.
16464988 Efficacy and safety of combination etanercept and methotrexate versus etanercept alone in 2006 Nov OBJECTIVE: To evaluate the efficacy and safety of etanercept (ETN) monotherapy compared with combination ETN and methotrexate (MTX) treatment in patients with rheumatoid arthritis who had an inadequate response to MTX monotherapy. (The response was defined by the presence of Disease Activity Score-28 joint count (DAS28) >or=3.2 or a combination of >or=5 swollen joints, >or=5 painful joints and erythrocyte sedimentation rate >or=10 mm/h.) METHODS: Patients with active rheumatoid arthritis taking MTX >or=12.5 mg/week for >or=3 months were included in this 16 week, randomised, open-label study. Patients were randomly assigned to either ETN (25 mg subcutaneous injection twice weekly) added to the baseline dose of MTX or ETN monotherapy. RESULTS: 315 patients were randomised to ETN (n = 160) or ETN plus MTX (n = 155). The primary end point, DAS28 (4) improvement of >1.2 units, was achieved by 72.8% and 75.2% of patients treated with ETN and those treated with ETN plus MTX, respectively, with no significant difference (p = 0.658) between the two groups. The European League Against Rheumatism response criteria of good or moderate response was attained by 80.0% of patients in the ETN group and by 82.4% of patients in the ETN plus MTX group. American College of Rheumatology 20%, 50% and 70% response rates achieved by both groups were also similar: 71.0% v 67.1%, 41.9% v 40.1% and 17.4% v 18.4%, respectively. The rates of adverse and serious adverse events were similar between the treatment groups. CONCLUSION: Both the addition of ETN to MTX and the substitution of ETN for MTX in patients with rheumatoid arthritis who had an inadequate response to MTX resulted in substantial improvements in clinical signs and symptoms and were generally well-tolerated treatment strategies for improving clinical signs and symptoms of rheumatoid arthritis.
18782656 Aromatase inhibitor-induced joint pain: melatonin's role. 2008 Dec Aromatase inhibitors (AIs) enjoy increasing use in breast cancer adjuvant therapy. But the joint pain associated with AIs significantly reduces patient adherence despite the clear survival benefits of this class of drugs. Two clues point to a novel hypothesis for this unexplained symptom. First, realizing that joint pain is associated with virtually all estrogen-depleting breast cancer treatments suggests that the cause is broader than this particular class of drugs. Second, the strongly circadian nature of these symptoms suggests circadian hormone involvement. This puts new light on some existing research findings: that estrogen depletion can increase pineal melatonin, that the ability of light to suppress pineal melatonin is more variable than once thought, and that an altered melatonin cycle is associated with rheumatoid arthritis patients, where identical circadian symptoms present. It is hypothesized that when AIs decrease estrogen levels, light-induced melatonin suppression (LIMS) loses efficacy, leading to an abnormal melatonin cycle as seen in rheumatoid arthritis patients, producing (via mechanisms not yet understood) the symptoms of morning stiffness. Not all frequencies of retinal light are equally effective at suppressing pineal melatonin; most artificial lighting has less relevant spectral density than sunlight. This hypothesis predicts that some patients can suppress the circadian joint pain associated with aromatase inhibitors merely by getting sufficient hours of daily retinal sunlight. A single patient history is discussed, in which a series of treatments had no effect on AI joint pain, while extended exposure to sunlight produced a definitive elimination of symptoms the next morning. To conclusively demonstrate the role of melatonin, light-emitting diodes of an appropriate frequency were mounted on a cap for the patient to wear. If worn first thing in the morning, the cap sharply curtailed the duration of morning stiffness. If worn for a sufficient number of hours during the day, the cap suppressed symptoms the next morning, just as sunlight did. Because of evidence for melatonin's oncostatic properties, this hypothesis potentially has implications beyond decreasing the number of patients that discontinue AIs. It may be that some portion of the survival benefit of AIs is due to their indirect effect on melatonin, not just their direct effect on estrogen.
18485021 Diffuse large B-cell lymphoma in a patient with rheumatoid arthritis treated with inflixim 2008 Jul Infliximab is a tumour necrosis factor (TNF)-alpha blocking drug classified as a biological response modifier. It has been suggested that the risk of malignancies, especially lymphomas, is increased in patients with rheumatoid arthritis (RA) treated with anti-TNF-alpha antibody therapy. We present a case of malignant lymphoma during the treatment of RA with infliximab and methotrexate.
18468425 [Antibodies to Klebsiella O-antigens in patients with seronegative spondyloarthropaties]. 2006 Mar OBJECTIVES: The pathogenesis of seronegative spondyloarthropathies is still unknown. A microbial etiology has been suggested. The aim of the study was to analyze the antibodies against Klebsiella O-antigens in serum of patients with seronegative spondyloarthropathies. METHODS: 30 patients with seronegative spondyloarthropathies, 20 with rheumatoid arthritis and 20 healthy volunteers were included in the study. The serum antibodies against Klebsiella O1 and O3 antigens were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: In serum of patients with seronegative spondyloarthropaties the antibodies against Klebsiella antigen O1 and O3 occur less frequently (6.67%) than in serum of patients with rheumatoid arthritis (35%) and that in serum of healthy subjects (40%). CONCLUSIONS: The results do not confirm the role of LPS in the pathogenesis of seronegative spondyloarthropthies, but on the other hand we could not exclude the concept that it may play an important role.
17057043 Abatacept. 2006 Nov 1 PURPOSE: The pharmacology, pharmacokinetics, indications, clinical efficacy, adverse effects, drug interactions, dosing, and administration of abatacept are discussed. SUMMARY: Abatacept is the first drug in a new class of agents known as selective costimulator modulators. Abatacept has been shown to decrease tumor necrosis factor (TNF)-alpha, which is important to the inflammatory response. Abatacept inhibits T-cell function but does not deplete T cells. Activated T cells are important in the inflammatory cascade, ultimately leading to joint inflammation and irreversible structural damage. In patients with rheumatoid arthritis, there is chronic inflammation of the synovial tissue lining the joint capsule. Abatacept is indicated for reducing the signs and symptoms of moderate to severe rheumatoid arthritis in adult patients who have had an inadequate response to at least one disease-modifying antirheumatic drug. Studies in adult patients with rheumatoid arthritis have evaluated abatacept in patients with an inadequate response to either methotrexate or TNF-alpha blocking agents. One trial showed that abatacept produced a favorable six-month clinical response in patients who had previously failed to respond to anti-TNF-alpha therapy. In a study of concurrent abatacept and methotrexate therapy, the addition of abatacept produced favorable outcomes in patients who were not adequately responding to methotrexate alone. CONCLUSION: Abatacept, a newly approved agent for the treatment of rheumatoid arthritis, has shown promising results in patients who have had an inadequate response to other treatment modalities. Abatacept therapy should be reserved for patients who have failed other time-tested treatment modalities, including TNF-alpha antagonists. Results from ongoing postmarketing studies will help determine abatacept's place in therapy.
17456462 Psychosocial and reported inflammatory disease correlates of self-reported heart disease i 2006 BACKGROUND: Past and recent research suggests that psychological and biological factors may increase women's risk of coronary heart disease (CHD). This study examined the prevalence and correlates of self-reported heart disease among Jewish women from the Negev, a socio-economically and culturally unique region in south of Israel. METHOD: A cross-sectional design was used. We interviewed over the phone 526 randomly-selected women (mean age: 44.3+/-14.2 years) about background variables (e.g., education), biomedical risk factors (e.g., body mass index or BMI), self-reported inflammatory diseases (rheumatoid arthritis or RA, urinary infections), psychosocial factors (depression, hopelessness, self-esteem, social-support) and self-rated health and heart disease. RESULTS: Prior physician diagnosis of heart disease was reported by 8.2% of women. Age, economic difficulties, diabetes, hypertension, BMI, physical exercise, RA and urinary infections were significantly associated with reported heart disease. Of all psychosocial factors considered, hopelessness and self-esteem significantly distinguished heart disease cases from non-cases. In a multiple logistic regression, poor self-esteem, RA and hypertension were significant independent correlates of self-reported heart disease. CONCLUSIONS: Pending replication with objective measures of heart disease and a prospective design, poor self-esteem and RA may prove to be new CHD risk factors in women.
17255353 TCRzetadim lymphocytes define populations of circulating effector cells that migrate to in 2007 May 15 The T-cell receptor zeta (TCRzeta) chain is a master sensor and regulator of lymphocyte responses. Loss of TCRzeta expression has been documented in infectious, inflammatory, and malignant diseases, suggesting that it may serve to limit T-cell reactivity and effector responses at sites of tissue damage. These observations prompted us to explore the relationship between TCRzeta expression and effector function in T cells. We report here that TCRzeta(dim) lymphocytes are enriched for antigen-experienced cells refractory to TCR-induced proliferation. Compared to their TCRzeta(bright) counterparts, TCRzeta(dim) cells share characteristics of differentiated effector T cells but use accessory pathways for transducing signals for inflammatory cytokine gene expression and cell contact-dependent pathways to activate monocytes. TCRzeta(dim) T cells accumulate in inflamed tissues in vivo and have intrinsic migratory activity in vitro. Whilst blocking leukocyte trafficking with anti-TNF therapy in vivo is associated with the accumulation of TCRzeta(dim) T cells in peripheral blood, this T-cell subset retains the capacity to migrate in vitro. Taken together, the functional properties of TCRzeta(dim) T cells make them promising cellular targets for the treatment of chronic inflammatory disease.