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ID PMID Title PublicationDate abstract
15617874 Autoimmune disorders result from loss of epigenetic control following chromosome damage. 2005 Multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis share common features in typical cases such as: adult onset, central nervous system problems, female predominance, episodes triggered by a variety of stresses, and an autoimmune reaction. At times, the different disorders are found in the same patient or close relatives. These disorders are quite complex but they may share a common mechanism that results in different, tissue-specific consequences based on the cell types in which the mechanism occurs. Here, it is hypothesized that DNA damage can lead to loss of epigenetic control, particularly when the damaged chromatin is distributed unevenly to daughter cells. Expression of genes and pseudogenes that have lost their epigenetic restraints can lead to autoimmune disorders. Loss of control of genes on the X chromosome and loss of control of polyamine expression are discussed as examples of this mechanism.
17127203 Infection and musculoskeletal conditions: Bacterial and opportunistic infections during an 2006 Dec Tumour necrosis factor alpha (TNF-alpha) plays a crucial role in host defence against bacterial infections. Summarizing the results, the findings of immunological and clinical research suggest a higher infection risk in rheumatoid arthritis and ankylosing spondylitis patients receiving anti-TNF treatment. This is especially true for granulomatous infections in patients treated with the monoclonal TNF-alpha antibodies infliximab or adalimumab. Furthermore, patients treated with TNF inhibitors have a higher susceptibility to infections because of their higher active and more severe disease. Therefore, patients receiving anti-TNF treatment should be closely monitored for serious infections. A rapid and sufficient treatment of infections that are not mild and transient is recommended. There are atypical signs and symptoms as well as atypical pathogen that should be considered. Patients should be educated about how to avoid infectious complications.
17110316 Malignancies and soluble tumor antigens in rheumatic diseases. 2006 Nov Paraneoplastic symptoms, caused by a malignancy, but not directly related to invasion by the tumor or its metastases are the result of a wide variety of tumor-derived biologic mediators like hormones, peptides, antibodies, cytotoxic lymphocytes, autocrine and paracrine mediators. Recognition of paraneoplastic syndromes is important, as it may lead to an early diagnosis of cancer. There is some evidence that systemic inflammatory diseases, such as rheumatoid arthritis (RA), lupus, scleroderma or dermatomyositis may increase the risk for the development of malignancies, predominantly lymphoproliferative disorders. However, reports are somewhat controversial. Immunosuppressive and cytotoxic drugs used in antirheumatic therapy, such as methotrexate, cyclophosphamide, azathioprine or anti-TNF biologicals may also lead to the development of such tumors. Tumor-associated antigens may be produced by inflammatory cells and their production may be increased in RA and other autoimmune diseases.
17056036 An estrogen receptor-beta agonist is active in models of inflammatory and chemical-induced 2006 Dec 28 ERB-041 (2-(3-Fluoro-4-hydroxyphenyl)-7-vinyl-1,3 benzoxazol-5-ol) is a selective estrogen receptor-beta agonist with activity in rodent models of rheumatoid arthritis and endometriosis. Clinical trials for these diseases are underway: however, the role of estrogen receptor-beta in modulating pain associated with inflammation remains unknown. These studies demonstrate that acutely administered ERB-041 is anti-hyperalgesic in preclinical models of chemical-induced and acute inflammatory pain, thus suggesting that ERB-041 may be useful for modulating pain associated with some types of inflammation.
17018000 Structural requirements of heparin and related molecules to exert a multitude of anti-infl 2006 Sep Chronic inflammatory diseases are common and still remain a therapeutic challenge for both efficacy and safety reasons. Hence, novel therapeutics addressing these issues would for example improve treatment of severe diseases such as psoriasis, rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis. Inappropriate leukocyte homing to the affected compartments is a common feature of these diseases. Heparin and related polysaccharides have been shown to interfere with leukocyte homing through a variety of effects distinct from their anticoagulant properties. In this review, data on heparin as an anti-inflammatory agent are presented. In addition, structure-activity requirements for the anti-inflammatory properties of heparin are discussed, which should aid the drug development based on structurally modified heparin or other sulfated carbohydrates for treatment of inflammatory diseases.
17009017 Accelerated apoptosis in SLE neutrophils cultured with anti-dsDNA antibody isolated from S 2006 Dec Increased numbers of apoptotic neutrophils are found in SLE, related to disease activity and levels of anti-dsDNA antibody. The mechanism of increased apoptosis is not clear, but anti-dsDNA antibody has been shown to induce apoptosis in neutrophils from normal subjects and in certain cell lines. In this study, polyclonal anti-dsDNA antibody was isolated from the serum of a patient with active SLE, and was shown to substantially accelerate apoptosis in neutrophils from SLE patients as compared with neutrophils from healthy control or rheumatoid arthritis subjects.
16956369 Therapeutic targeting of molecules involved in leukocyte-endothelial cell interactions. 2006 Oct Inflammation is traditionally viewed as a physiological reaction to tissue injury. Leukocytes contribute to the inflammatory response by the secretion of cytotoxic and pro-inflammatory compounds, by phagocytotic activity and by targeted attack of foreign antigens. Leukocyte accumulation in tissues is important for the initial response to injury. However, the overzealous accumulation of leukocytes in tissues also contributes to a wide variety of diseases, such as atherosclerosis, chronic inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, vasculitis, systemic inflammatory response syndrome, juvenile diabetes and psoriasis. Many therapeutic interventions target immune cells after they have already migrated to the site of inflammation. This review addresses different therapeutic strategies, used to reduce or prevent leukocyte-endothelial cell interactions and communication, in order to limit the progression of inflammatory diseases.
16819203 Folate-linked lipid-based nanoparticles deliver a NFkappaB decoy into activated murine mac 2006 Jul Activated macrophages are the key effector cells in rheumatoid arthritis (RA) and secrete multiple mediators of inflammation including proinflammatory cytokines. We investigated delivery of a nuclear factor kappa B (NFkappaB) decoy by folate-linked lipid-based nanoparticles (NP-F) into murine macrophages. The expression of folate receptor (FR) in RAW264.7 cells activated by lipopolysaccaride was confirmed by strong expression of FR mRNA, and association of FITC-labeled folate-BSA conjugate. When transfected via NP-F, the NFkappaB decoy was strongly detected in the cytoplasm, and an inhibitory effect on the translocation of NFkappaB into the nucleus was observed at 0.03 microM of the decoy, suggesting that NP-F effectively delivered the NFkappaB decoy into the cytoplasm. This information is of value for the design of NFkappaB decoy carrier systems targeting FR in activated macrophages in gene therapy for autoimmune diseases such as RA.
16332285 Immunomodulatory effect of various anti-parasitics: a review. 2006 Mar This paper reviews the immunomodulatory effects (immunosuppression or immunoactivation) of various anthelmintics including levamisole, fenvalerate, dieldrin, carbofuran, aminocarb, thiabendazole, fenbendazole, oxfendazole and ivermectin. The induced modulation of immune function may occur via direct and/or indirect mechanisms. The immunomodulatory effects of these anti-parasitics have been studied in a variety of bacterial (e.g. brucellosis, salmonellosis, paratuberculosis, mastitis), viral (e.g. infectious bovine rhinotracheitis, Herpes, foot and mouth disease), parasitic (e.g. onchocerciasis, coccidiosis, ascariasis, schistosomiasis) and neoplastic diseases. Some antiparasitics have also been used to boost immunity in a number of human diseases including leprosy, Hodgkin's disease, rheumatoid arthritis, and in adjuvanted therapy of colorectal cancer. The ability to stimulate the immune response of animals offers a new means of disease intervention. Future research on immunomodulatory effects of anti-parasitics, for humans and domestic farm animals, will provide additional methods of treating immunosuppressed subjects. The immunopotentiating or immunosuppressing activity of anti-parasitics will dictate whether co-administration of vaccines and anthelmintics or administration of vaccines during the window of immunoactivation is justified or not.
16331786 Measurement of joint space width and erosion size. 2005 Dec Measurement of radiographic abnormalities in metric units has been reported by several investigators during the last 15 years. Measurement of joint space in large joints has been employed in a few trials to evaluate therapy in osteoarthritis. Measurement of joint space width in small joints has been reported by several investigators but has not yet found a place in clinical trials in rheumatoid arthritis or osteoarthritis. We review methods for measuring joint space width in finger, toe, and wrist joints; special attention is given to how the joint edges are found, the method used to measure distance between joint margins, size of an area of the sampled joint, and reproducibility of measurements. Methods for measurement of erosion size, which have had less attention, are briefly discussed.
16213771 Is restless legs syndrome underrecognized? Current management. 2006 Jul Restless legs syndrome (RLS) is a poorly understood sensory-motor neurological disorder whose prevalence in Caucasian populations ranges from 10% to 15%. The patient reports unpleasant sensations in the lower limbs with dysesthesia resulting in an urge to move the legs. The symptoms occur during periods of inactivity, increasing in the evening and at night. Moving the legs provides relief. In 80% of cases, polysomnography shows periodic leg movements during sleep. Patients with idiopathic RLS often report similar symptoms in family members. Secondary RLS may be due to medications, diabetes mellitus, renal failure, iron deficiency, neurological disorders, or rheumatoid arthritis. In secondary RLS, the management rests on treatment of the cause. Symptomatic treatment is warranted in patients with moderate-to-severe symptoms that adversely affect the quality of life. Dopaminergic agents are tried first. When they fail or induce adverse effects, weak opioids, benzodiazepines, anticonvulsants or, if needed, strong opioids, may be used.
15977574 [Three sisters of pulmonary Mycobacterium avium complex disease]. 2005 May We reported three sisters of pulmonary Mycobacterium avium complex (MAC) disease. The oldest sister was complaining of bloody sputum, and cultures were positive for M. avium. By monotherapy with clarithromycin, symptom and imaging findings had shown no progression for six years. The second sister was complaining of productive cough, and cultures were positive for M. intracellulare. Her symptom and imaging findings had shown no progression for seven years without any treatment. The third sister had rheumatoid arthritis and diabetes mellitus, and cultures were positive for M. intracellulare. Although she received chemotherapy with rifampicin, clarithromycin, ethambutol, and kanamycin, symptom and imaging findings had progressed gradually. She died of respiratory failure four years later. Autopsy findings revealed no disseminated MAC disease. The results which three cases showed different isolate patterns and clinical courses suggest the importance of underlying anti-mycobacterial immunological impairment and defects of local host defense rather than virulence of infected strains as the pathogenesis of pulmonary MAC disease.
15931215 Treatment of severe autoimmune disease by stem-cell transplantation. 2005 Jun 2 Transplantation of haematopoietic stem cells--cells capable of self renewing and reconstituting all types of blood cell--can treat numerous lethal diseases, including leukaemias and lymphomas. It may now be applicable for the treatment of severe autoimmune diseases, such as therapy-resistant rheumatoid arthritis and multiple sclerosis. Studies in animal models show that the transfer of haematopoietic stem cells can reverse autoimmunity, and several mechanistic pathways may explain this phenomenon. The outcome of ongoing clinical trials, as well as of studies in patients and animal models, will help to determine the role that stem-cell transplantation can play in the treatment of autoimmune diseases.
15838738 Membranous proliferation on the posterior surface of an intraocular lens after Nd:YAG lase 2005 Mar BACKGROUND: We report on three patients who showed a rare complication, centripetal membranous proliferation from the posterior capsulotomy edge onto the posterior surface of an intraocular lens (IOL), 3 to 6 months after neodymium:YAG (Nd:YAG) capsulotomy. CASES: These three patients had juvenile rheumatoid arthritis, retinitis pigmentosa, and sarcoidosis, respectively, prior to cataract surgery. OBSERVATIONS: Elschnig's pearls developed in the eyes of all three patients after cataract surgery, and were treated by Nd:YAG laser. However, membranous proliferation continued, and Nd:YAG laser treatment was required a second time to disrupt the proliferating fibrous membrane and achieve resolution of the patients' symptoms. CONCLUSIONS: Common factors in our cases and cases in the literature were that the IOLs were biconvex and made of polymethyl methacrylate. Ophthalmologists should be aware that after cataract surgery, lens epithelial cells can proliferate onto any surface that provides adequate protein nourishment.
15763890 Tetraspanin-Fc receptor interactions. 2005 Feb The tetraspanins are a superfamily of membrane glycoproteins which facilitate the interaction of membrane and intracellular signalling molecules (e.g., integrins, pro-growth factors and their receptors, protein kinase-C) in the formation of membrane signalling microdomains (sometimes referred to as the tetraspanin web). A proximal localisation/association of tetraspanins with Fc receptors (FcR) has been implied by the repeated rediscoveries of tetraspanins as the targets of antibodies which activate platelets and other blood cells through co-ligation of FcR. Direct evidence of tetraspanin-FcR interactions has come from immunoprecipitation and co-immunofluorescence studies. The functional effects of this interaction remain unclear, but tetraspanins have been identified as negative regulators of FcR signalling independently of co-ligation, indicating potential roles in modulating FcR function in co-ordination with the activity of other signalling/adhesion molecules in the tetraspanin web. Given their capacity to influence FcR signalling, tetraspanins could provide specific therapeutic targets for immune disorders including rheumatoid arthritis, asthma and allergies.
27157077 Nonprosthesis Orthopedic Applications of (18)F Fluoro-2-Deoxy-d-Glucose PET in the Detecti 2006 Apr This article describes the impact of [(18)F]2-fluoro-2-deoxy-d-glucose (FDG) PET in the diagnosis of non-prosthesis-related orthopedic infections and inflammation. FDG-PET has an excellent sensitivity in the detection of osteomyelitis (OM). Early data indicate that FDG-PET may be more specific than MRI in diagnosing OM. The role of the combination of FDG and PET-CT in the diagnosis of OM is likely to be determined as this combination is used on a routine basis. Early data from studies in rheumatoid arthritis indicate that FDG-PET is highly accurate in early diagnosis and that it provides results comparable to the most advanced conventional techniques.
17149055 Sphygmomanometry-evoked allodynia--a simple bedside test indicative of fibromyalgia: a mul 2006 Dec BACKGROUND: One of the 2 classification criteria for fibromyalgia (FM) is the presence of tender points on specific anatomic sites. It has been established that these tender points reflect a state of generalized allodynia (defined as pain resulting from a stimulus that does not normally provoke pain). Patients with FM often describe pain elicitation during blood pressure testing (sphygmomanometry). OBJECTIVE: The objective of this study was to define if a universally used clinical test, sphygmomanometry, is helpful in the identification of patients with FM. METHODS: The authors conducted a prospective multicenter study in 3 different public rheumatology outpatient services. Each center studied 20 patients with FM, 20 with rheumatoid arthritis, 20 with osteoarthritis, and 20 healthy individuals. The following question was asked of each participant: "When I take your blood pressure, tell me if the cuff's pressure brings forth pain." The blood pressure cuff was inflated at an approximate rate of 10 mm Hg per second up to 180 mm Hg or to the point when pain was elicited. RESULTS: Sixty-nine percent of patients with FM had sphygmomanometry-evoked allodynia in contrast to 10% of patients with osteoarthritis, 5% with rheumatoid arthritis, and 2% of healthy individuals (P < 0.001). The mean blood pressure value at which allodynia was elicited was lower in patients with FM (143 +/- 40 mm Hg) when compared with the other 3 groups (176 +/- 11 mm Hg) or higher (P < 0.001). In patients with FM, there was a significant negative correlation between the blood pressure value at which allodynia developed and total Fibromyalgia Impact Questionnaire (FIQ) score, number of tender points, and the FIQ visual analog scales for pain intensity and fatigue (P < 0.05). The test yields a diagnostic sensitivity for FM of 0.7, specificity 0.96, positive predictive value 0.86, and negative predictive value 0.91. CONCLUSIONS: In this developmental study of patients attending rheumatology clinics, the generation of pain during blood pressure testing was strongly associated with the diagnosis of FM. This robust linkage probably reflects a tautologic phenomenon. A sine qua nonelement for FM diagnosis is the presence of tender points in discrete anatomic sites. These tender points in turn reflect a state of generalized mechanical allodynia that can be locally elicited by the cuff pressure during blood pressure testing. Sphygmomanometry is a simple bedside test that may be useful in the recognition of patients with FM. Blood pressure testing is a universal procedure in all clinical environments. Based on our results, we suggest searching for FM features in any person who has sphygmomanometry-evoked allodynia.
16380750 [Assessment of circadian rhythm in pain and stiffness in rheumatic diseases according the 2005 Dec BACKGROUND: Many researchers have used paper diaries in an attempt to capture patient experience. However, patient non-compliance with written diary protocols is a serious problem for researchers. Electronic patient experience diaries (eDiary) facilitate Ecologic Momentary Assessment (EMA) study designs by allowing the researcher to administer flexible, programmable assessments and mark each record with a time and date stamp. OBJECTIVES: The objectives of the current study were to evaluate methodological issues associated with real-time pain reports (EMA) using electronic patient experience diaries, to quantify compliance (percentage of the total number of diary reports scheduled that were actually completed), and to examine the circadian rhythm in pain and stiffness of patients with rheumatic diseases in an ecologically valid manner. METHODS: In this cross-sectional study we examined 49 patients with rheumatic diseases (14 patients with rheumatoid arthritis, 18 with fibromyalgia and 17 with osteoarthritis of the knee), attending the care facilities of the Department of Rheumatology of Università Politecnica delle Marche. All patients fulfilling the American College of Rheumatology (ACR) criteria. The assessment of pain and stiffness in all patients were repeated seven times a day (8 A.M., 10 A.M., 12 A.M., 2 P.M., 4 P.M., 6 P.M. and 8 P.M.) on seven consecutive days using an electronic diary (DataLogger® - Pain Level Recorder). A datalogger is newly developed electronic instrument that records measurements of pain and stiffness over time. Dataloggers are small, battery-powered devices that are equipped with a microprocessor. Specific software is then used to select logging parameters (sampling intervals, start time, etc.) and view/analyse the collected data. Compliance is based on the time and date record that was automatically recorded by the devices. RESULTS: Using the data from the electronic diary, we determined that the average verified compliance rate for pain and stiffness were 93.8 and 93.6%, respectively. The two highest compliance rates were observed in patients with rheumatoid arthritis (95.6 and 95.2%, respectively). There were no statistically significant difference in compliance between females and males or patients above or below 60 years old. Significant circadian rhythms in patients with RA and OA of the knee were detected in pain and stiffness. No rhythm in pain or stiffness was observed in subjects with fibromyalgia. CONCLUSIONS: We conclude that collection of subjective data using electronic diary in rheumatologic setting is a feasible method than can be adopted with high compliance rates across a range of patient demographic subgroups. The identification of diurnal cycles of self-reported pain and stiffness, using EMA method, has important implications for patients with respect to planning their daily activities and in developing individual therapeutic programs with respect to diurnal variability, which therefore may be more effective.
16899499 Individual fracture risk and the cost-effectiveness of bisphosphonates in patients using o 2007 Mar OBJECTIVES: There are few data on the cost-effectiveness of bisphosphonates with oral glucocorticoids (GCs). An individual patient-based pharmaco-economic model was developed. METHODS: Data were obtained from a cohort of oral GC users aged 40+ (n = 190 000) in the UK General Practice Research Database. Individualized fracture and mortality risks were calculated specific for age, sex, daily and cumulative GC dose, indication and other clinical risk factors. UK costs of medication and direct costs of fracture were obtained from National Institute for Clinical Excellence and used to estimate costs per quality-adjusted life-year (QALY) gained and fracture prevented for bisphosphonates in patients treated for 5 yrs with GCs. RESULTS: With the use of 5 mg GCs daily, the cost per one QALY gained with bisphosphonates was 41k UK pounds (95% confidence intervals 22-72k) in women aged <60 [men 40k pounds (29-54k)], 17k pounds (13-24k) in women aged 60-79 [men 43k pounds (31-60k)], 5k pounds(3-6k) in women aged 80+ [men 35k pounds (25-46k)]. With 15 mg GC, these figures were 17k pounds (14-21k), 13k pounds (10-16k) and 15k pounds (9-26k) in women and 22k pounds (17-26k), 34 pounds (23-53k) and 33k pounds (27-42k) in men, respectively. When stratifying by overall fracture risk and life expectancy at the start of GC therapy, cost per QALY increased with decreasing life expectancy. Patients with rheumatoid arthritis had comparatively better cost-effectiveness, given higher fracture risk and better life expectancy. CONCLUSIONS: The cost-effectiveness of bisphosphonates varied substantially. Bisphosphonates can be considered cost-effective in patients with higher fracture risks, such as elderly patients (with a life expectancy over 5 yrs), and younger patients with a fracture history, low body mass index, rheumatoid arthritis or using high GC doses.
15981083 Association between circulating levels of the novel TNF family members APRIL and BAFF and 2005 May B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are members of the tumour necrosis factor superfamily. We have examined circulating BAFF and APRIL in relation to serological deviations and lymphoid organization in the salivary glands of the chronic, autoimmune disorder Sjögren's syndrome. Lymphoid organization in the shape of ectopic germinal centers were detected in 33 of 130 consecutive minor salivary gland biopsies and coincided with increased focus score and elevated levels of serum IgG. Follicular dendritic cell networks, proliferation of mononuclear cells and altered B/T cell ratio also separated the two subgroups. Serum levels of sBAFF and sAPRIL were increased in Sjögren's syndrome compared to healthy blood donors, especially in anti-Ro/La+ patients. Though the differences could not be related to germinal center formation, positive correlations between serum levels of sBAFF and sAPRIL, focus score and IgG denotes their possible role in the disease progression of primary Sjögren's syndrome.