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ID PMID Title PublicationDate abstract
16569363 Infliximab in recalcitrant severe atopic eczema associated with contact allergy. 2006 Jan Infliximab is an anti-tumour necrosis factor (TNF)-alpha chimeric monoclonal antibody which is effective in diseases associated with a T-helper (Th) 1 response, such as rheumatoid arthritis, Crohn's disease and psoriasis. There are sporadic case reports of atopic dermatitis (AD) induced or precipitated by anti-TNF-alpha therapy, which have been attributed to the switch towards Th2-mediated reactions. We report the case of a 30-year-old man with long-standing severe AD associated with contact allergy and poorly responding to conventional treatments. The use of infliximab resulted in a dramatic amelioration of AD lesions and pruritus, persisting at follow-up examinations over a 3-year period. Probably, the unexpected response to infliximab therapy in this case might be due to some peculiar features of AD in our patient (i.e. chronic-continuous course and concomitant contact allergy) which could have been responsible for a more preponderant recruitment of Th1 cells as compared to common forms of AD.
16526326 Pancytopenia after low dose methotrexate therapy in a hemodialysis patient: case report an 2006 Methotrexate (MTX) is widely used in the treatment of rheumatoid arthritis (RA) with a side effect of pancytopenia. However, only a few cases of severe pancytopenia caused by low-dose MTX therapy have been reported, and the condition is rarely reported in uremic patients on dialysis therapy. We thereby report a hemodialysis patient who developed severe pancytopenia after oral treatment with low-dose MTX for RA. A 55-year-old woman who had been on regular hemodialysis treatment for 7 yr suffered from RA for 10 yr. She was regularly treated with celecoxib, prednisolone, and sulfasalazine in the past year. Because of the increasing arthralgia, 7.5 mg per week MTX was prescribed 3 months before admission. Stomatitis, fever, general fatigue, multiple skin carbuncles, and easy bruising developed after a cumulative dose of 90 mg. Pancytopenia was found at admission and the nadir of white blood cell count was 250/microL with 28% neutrophils, hematocrit was 22%, and platelet count was 6000/microL. Eosinophil counts increased from 11.5% initially to 26.1% on the sixth admission day. Transfusion with red blood cells and platelets, and appropriate antibiotics and folic acid were prescribed. She continued receiving regular hemodialysis and eventually recovered within 3 weeks.
16421089 PEG-derivative effectively modifies the characteristics of indomethacin-PLGA microspheres 2005 Nov The aim of this study was to obtain biodegradable indomethacin microspheres for intra-articular administration in rheumatoid arthritis, where angiogenic processes are involved. Indomethacin concentrations to achieve an anti-angiogenic effect would be five-times higher than an anti-inflammatory. Microspheres were prepared by solvent evaporation using PLGA. Indomethacin is a poor water-soluble drug with it being possible that dissolved and non-dissolved drug co-exist within the polymeric matrix resulting in rapid release. To control this release, an oil-PEG-derivative was incorporated, producing changes in morphology, crystallinity and indomethacin release. To minimize the amount of microspheres administered, a two-factor five-level central rotable composite 2(2)+star design was employed with two independent variables: indomethacin percentage and PEG-derivative percentage. The optimum formulation showed mean encapsulation efficiency of 94.3+/-2.2% and released 7.99+/-0.25 microg indomethacin/day/mg microspheres for 21 days. A dose of 20-50 mg of this formulation could be appropriate to achieve both anti-angiogenic and anti-inflammatory effects. Preliminary cytotoxicity studies performed in rat splenocytes showed an adequate cell viability.
16401407 Drug disease interactions: role of inflammatory mediators in disease and variability in dr 2005 Dec 16 Expression of both pro- and anti-inflammatory mediators are influenced by various factors such as rheumatic diseases, myocardial infarction, angina, aging, obesity and pharmacotherapy. This has therapeutic consequences. Clearance of highly bound and efficiently metabolized drugs may be reduced in the presence of inflammation amounting to increased circulating drug concentration. In the meantime, various cardiovascular receptors are down-regulated in the presence of pro-inflammatory mediators. Consequently, conditions such as rheumatoid arthritis, aging and obesity results in reduced response to drugs such as verapamil despite increased drug concentration. The inflammatory response is a complex cascade of non-specific events resulting in excessive generation of inflammatory mediators such as cytokines, C-reactive protein and nitric oxide by cells of the innate (macrophages, monocytes, neutrophils) and adaptive (T-lymphocytes) arms of the immune system. T-lymphocytes secrete various pro- and anti-inflammatory cytokines during an inflammatory event. In general, two distinct subpopulations of these T-helper cells exist, anti-inflammatory Th2 and pro-inflammatory Th1. As a common rule, Th1 cytokines suppress Th2 and vice-versa. Hence, a balance of these activities is desired. Drugs such as antirheumatoid agents, angiotensin II blockers and hydroxymethyl-glutaryl-CoA reductase inhibitor (statin) may help to restore the Th1/Th2 balance. In general, at least for some conditions, the challenge of therapeutic drug monitoring will be more useful if expression of inflammatory mediators is also taken into account. In addition, some of the intersubject variation in pharmacotherapy and clinical trails may be attributed to variations in the inflammatory mediator's concentration. A detail list of conditions and drugs that influence expression of the inflammatory mediators are provided and potential therapeutic consequences are discussed.
16379131 Effects of a cognitive-behavioral program for women with multiple sclerosis. 2005 Oct The purpose of this quasi-experimental study was to evaluate the effectiveness of a cognitive-behavioral intervention for women with multiple sclerosis (MS). Thirty-seven adult women with MS participated in a group-based intervention program titled "Beyond MS," which was led by master's-prepared psychiatric nurses. For participants, the program involved reading a manual and meeting for five weekly group sessions. Perceived health competence, coping behaviors, psychological well-being, quality of life, and fatigue were measured at four time periods: 5 weeks before the beginning of the intervention, immediately before the intervention, at the end of the 5-week intervention, and at a 6-month follow-up. There were significant improvements in the participants' perceived health competence (p < .01), indices of adaptive and maladaptive coping (p < .04), and most measures of psychological well-being (p < .05) from pre- to postintervention. The positive changes brought about by this relatively brief intervention program were maintained during the 6-month follow-up period. This cognitive-behavioral intervention has also been used effectively in the rheumatoid arthritis population and may be adaptable to benefit individuals with other chronic conditions.
16354277 Therapeutic apheresis--state of the art in the year 2005. 2005 Dec Therapeutic apheresis is an extracorporeal blood purification method for the treatment of diseases in which pathological proteins or cells have to be eliminated. Selective plasma processing is more efficient in pathogen removal than unselective plasma exchange and does not require a substitution fluid like albumin. This overview presents the various selective devices for the treatment of plasma (plasmapheresis) and blood cells (leukocyte apheresis). Prospective randomized trials were performed for the treatment of age-related macular degeneration (Rheopheresis), sudden hearing loss (heparin-induced lipoprotein precipitation [HELP]), rheumatoid arthritis (Prosorba), dilative cardiomyopathy (Ig-Therasorb, Immunosorba), acute-on-chronic liver failure (molecular adsorbent recirculating system [MARS]), and ulcerative colitis (Cellsorba). Prospective non-randomized controlled trials were carried out treating hypercholesterolemia (Liposorber) and crossmatch-positive recipients before kidney transplantation (Immunosorba). Uncontrolled studies were done for ABO-incompatibility in living donor kidney transplantation (KT) (Glycosorb), acute humoral rejection after KT (Immunosorba) and acute liver failure (Prometheus). According to the 2002 International Apheresis Registry covering 11428 sessions in 811 patients, 79% of the patients showed an improvement of their condition by apheresis and only a few sessions were fraught with adverse effects (AE). The major AE were blood access difficulties (3.1%) and hypotension (1.6%). In summary, therapeutic apheresis is a safe and effective procedure for the treatment of diseases refractory to drug therapy.
16338212 2nd conference on heart, rheumatism and autoimmunity, Pescara, Italy, May 19-20, 2005. 2006 Jan Systemic autoimmune diseases, which comprise a family of conditions which share common pathogenetic mechanisms, are frequently associated to cardiac involvement and to a high prevalence of ischemic coronary events often occurring at a younger age than in normal population. A large increase in mortality is related to premature atherosclerosis with coronary artery disease and stroke in patients with connective tissue diseases. Coronary heart disease is responsible for 40-50% of the death of patients with rheumatoid arthritis. Moreover, a growing body of evidence supports the view that autoimmune mechanisms are involved in the pathogenesis of cardiovascular disease. Inflammatory heart disease is a rising concern worldwide. Similar mechanisms link autoimmune diseases, including the association of increased disease with proinflammatory cytokines and the importance of regulatory mechanisms in the control of chronic inflammation. The role of the immune system in modulating atherosclerosis has recently been well documented. Studies have revealed that cellular and humoral immunity plays crucial roles in atherogenic plaque formation. This includes macrophages, CD4+ T cells and dendritic cells as well as autoantigens such as oxidized low-density lipoprotein (oxLDL), heat shock proteins and beta2-glycoprotein I. The inflammatory component is not localized to the "culprit" plaque, but it is diffused to the entire coronary vascular bed, and involves also the myocardium. The aim of the conference (2nd conference on heart, rheumatism and autoimmunity) was to focus the attention of the participants on some pathogenetic, clinical and therapeutic aspects at the boundary between cardiology and rheumatology and to encourage the debate among clinicians and basic researchers with different backgrounds and experiences.
16284445 Enhanced expression of CD69 and CD25 antigen on human peripheral blood mononuclear cells b 2005 Oct Several clinical reports have suggested that prolactin (PRL) plays an important role in the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). We have investigated the influence of PRL on immune system, by evaluating the effects of PRL on the expression of CD69 and CD25 on human peripheral blood mononuclear cells (PBMCs). Human PBMCs obtained from healthy female volunteers were incubated with phytohemagglutinin (PHA) in the presence or absence of various concentrations of PRL. The expression of CD69 and CD25 was monitored using immunofluorescence staining and flow cytometry. PRL significantly enhanced the expression of CD69 and CD25 on activated PBMCs compared with that in the absence of PRL (p<0.05, paired t-test). Increasing doses of PRL enhanced the expression of CD69 up to 2 microg/ml and CD25 up to 1 microg/ml. The enhanced expression of CD69 was observed on CD8+ T lymphocytes but not on CD4+ T lymphocytes. Our data suggest that PRL can significantly enhance the expression of CD69 and CD25 molecule on human PBMCs when induced by PHA. However, PRL would have to be at optimal concentration in order to enhance their expression.
16227150 PD-1/PD-L pathway and autoimmunity. 2005 Aug Programmed cell death 1 (PD-1) was isolated in 1992 by subtractive-hybridization technique, as a molecule whose expression is enhanced by apoptotic stimuli. Since then we have been analyzing the function of PD-1 in the regulation of immune responses. Generation of PD-1 deficient mice, pathophysiological analyses of autoimmune diseases in PD-1 deficient mice, identification of two ligands, and analyses of downstream events of PD-1 revealed that PD-1 prevents autoimmunity by inhibiting activation of self-reactive lymphocytes. These findings were further applied on human autoimmune diseases and single nucleotide polymorphisms (SNPs) on human PD-1 gene have been reported to link with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and type I diabetes.
16199044 Finite element modelling of glenohumeral kinematics following total shoulder arthroplasty. 2006 Due to the shallowness of the glenohumeral joint, a challenging but essential requirement of a glenohumeral prosthesis is the prevention of joint dislocation. Weak glenoid bone stock and frequent dysfunction of the rotator cuff, both of which are common with rheumatoid arthritis, make it particularly difficult to achieve this design goal. Although a variety of prosthetic designs are commercially available only a few experimental studies have investigated the kinematics and dislocation characteristics of design variations. Analytical or numerical methods, which are predictive and more cost-effective, are, apart from simple rigid-body analyses, non-existent. The current investigation presents the results of a finite element analysis of the kinematics of a total shoulder joint validated using recently published experimental data for the same prostheses. The finite element model determined the loading required to dislocate the humeral head, and the corresponding translations, to within 4% of the experimental data. The finite element method compared dramatically better to the experimental data (mean difference=2.9%) than did rigid-body predictions (mean difference=37%). The goal of this study was to develop an accurate method that in future studies can be used for further investigations of the effect of design parameters on dislocation, particularly in the case of a dysfunctional rotator cuff. Inherently, the method also evaluates the glenoid fixation stresses in the relatively weak glenoid bone stock. Hence, design characteristics can be simultaneously optimised against dislocation as well as glenoid loosening.
16195663 Comparative clinicopathology of obliterative bronchiolitis and diffuse panbronchiolitis. 2006 BACKGROUND: The progressive airway obliteration caused by obliterative bronchiolitis (OB) has been widely noted in the world. In contrast, the obstructive respiratory disorder caused by diffuse panbronchiolitis (DPB) has been reported mainly from Japan. Therefore, there might be a considerable overlap between OB and DPB in Japan. OBJECTIVES AND METHODS: To clarify the clinicopathological similarities as well as the differences between OB and DPB, 15 patients with OB and 6 patients with DPB were evaluated clinicopathologically. RESULTS: The underlying disorders in OB were graft-versus-host disease (GVHD) in 7, rheumatoid arthritis in 3, Kartagener's syndrome in 2, and polymyositis/dermatomyositis, non-tuberculous mycobacterial disease and mycoplasmal pneumonia in one each. The lung pathology demonstrated that the primary obstructive lesions were in the membranous bronchioli in OB. In contrast, they were confined to the respiratory bronchioli in DPB. In addition, OB was classified into two major morphologic types, namely, constrictive and cellular. Clinical manifestations included cough and/or dyspnea in 13 with OB and in 6 with DPB, chronic parasinusitis in 3 with cellular OB and in 6 with DPB. The pulmonary function tests revealed obstructive impairments in all patients with OB and DPB. The chest CT images showed small centrilobular nodules in 64% of those with OB and in all with DPB. The prognosis of constrictive OB was worse than that of cellular OB and DPB. CONCLUSIONS: This study demonstrated that histopathologically marked differences existed between OB and DPB, although striking similarities in clinical manifestations were also noted in both diseases.
16169773 The therapeutic potential of anti-CD20 "what do B-cells do?". 2005 Dec B-cells play a major role in the immunopathogenesis of autoimmune diseases. Not only do they produce autoantibodies, but they regulate other cell types, secrete cytokines, and present antigens. They are thus potential targets for therapeutic intervention. CD20 is a B-cell specific cell surface molecule of uncertain function. An anti-CD20 chimeric mAb (rituximab) has been FDA approved for treatment of B-cell lymphomas since 1997. Rituximab also depletes normal B-cells by several mechanisms, including ADCC. Over the past seven years, it has shown promise in a number of autoimmune diseases in phase I trials and anecdotal reports. Efficacy in rheumatoid arthritis has already been demonstrated in randomized control trials (RCTs), and RCTs in SLE, inflammatory myositis, and ANCA associated vasculitis are under way. Safety does not appear to be a major problem, but continued vigilance is warranted. The increased use of rituximab, other anti-CD20 agents, and other B-cell targeting therapies holds great promise for substantial clinical benefits, as well as providing special opportunities to understand better disease pathogenesis.
16014531 The ananti-alpha-actinin test completes ananti-DNA determination in systemic lupus erythem 2005 Jun In murine systemic lupus erythematosus (SLE) models, nephritogenic anti-dsDNA IgG has been shown to cross-react with a kidney antigen, alpha-actinin, and to be critical in renal pathogenesis. In humans, studies of anti-alpha-actinin antibodies (Abs) are scarce, and these antibodies remain to be evaluated. We have thus far tested sera from patients with SLE (n = 103), rheumatoid arthritis (RA, n = 93), and primary Sjögren syndrome (pSS, n = 34), and from healthy subjects (n = 160), for the presence of anti-alpha-actinin and anti-DNA Abs. The latter were tested using several methods [IIF on Crithidia luciliae (Crit) and ELISA using dsDNA]. Anti-alpha-actinin Abs were confirmed by Western blot. Sera from 23 of 103 SLE patients, 3 of 93 RA patients, 1 of 33 pSS patients, and 1 of 160 controls scored positive for anti-alpha-actinin Abs. In SLE, the positivity was significantly associated with anti-dsDNA reactivity (22 of 23): 19 of 23 sera were alpha-actinin-positive/dsDNA-positive and 13 were alpha-actinin-positive/Crit-positive. Few cases were alpha-actinin-positive/dsDNA-negative: 1 SLE, 3 RA, and 1 control. Furthermore, anti-alpha-actinin Abs have been detected at high level before or at the early stage of lupus nephritis when compared with active and inactive SLE without kidney manifestations.
15989480 Distribution of radiation in synovectomy of the knee with 166Ho-FHMA using image fusion. 2005 Jun BACKGROUND: Radiation synovectomy is an effective technique for the treatment of chronic synovitis in patients with rheumatoid arthritis (RA), and is an alternative for surgical synovectomy. Holmium ferric hydroxide macroaggregates (166Ho-FHMA) is suitable for radiation synovectomy, especially because it emits high-energy beta particles and a smaller proportion of low-energy photons that are suitable for gamma-camera imaging. OBJECTIVE: The aim of this study was to develop a method to fuse 166Ho-FHMA single photon emission computed tomography (SPECT) and magnetic resonance (MRI) images, to show the distribution of 166Ho-FHMA inside the joint with images that localize synovitis. METHODS: The knees of 6 patients with RA were treated with 166Ho-FHMA. (99m)Tc-human immunoglobulin ((99m)Tc-HIG) SPECT images and MRI images were taken before 166Ho-FHMA injections. 166Ho-FHMA SPECT images were taken 4, 28, and 40 hours after injections. SPECT and MRI images were merged using a specific image fusion method, called mutual information algorithm, to study associations between anatomical and metabolic information from these images. RESULTS: Fusion of SPECT and MRI images indicated that intensity of radioactivity was associated with the amount of synovitis. Activity distribution of 166Ho-FHMA could be registered using anatometabolic images. CONCLUSIONS: A new method to fuse the distribution of radiation in the synovectomy of the knee was developed using SPECT/MRI image registration. Image registration of SPECT and MRI can be used to determine the activity distribution of radioisotopes in relation to synovitis.
15984902 The science of megestrol acetate delivery: potential to improve outcomes in cachexia. 2005 Cachexia, usually defined as the loss of >5% of an individual's baseline bodyweight over 2-6 months, occurs with a number of diseases that includes not only AIDS and advanced cancer but also chronic heart failure, rheumatoid arthritis, chronic obstructive pulmonary disease, Crohn disease, and renal failure. Anorexia is considered a key component of the anorexia-cachexia syndrome. Progestogens, particularly megestrol acetate, are commonly used to treat anorexia-cachexia. The mechanism of action of megestrol is believed to involve stimulation of appetite by both direct and indirect pathways and antagonism of the metabolic effects of the principal catabolic cytokines. Because the bioavailability of megestrol acetate directly affects its efficacy and safety, the formulation was refined to enhance its pharmacokinetics. Such efforts yielded megestrol acetate in a tablet form, followed by a concentrated oral suspension form, and an oral suspension form developed using nanocrystal technology. Nanocrystal technology was designed specifically to optimize drug delivery and enhance the bioavailability of drugs that have poor solubility in water. Megestrol acetate nanocrystal oral suspension is currently under review by the US FDA for the treatment of cachexia in patients with AIDS. Preclinical pharmacokinetic data suggest that the new megestrol acetate formulation has the potential to significantly shorten the time to clinical response and thus may improve outcomes in patients with anorexia-cachexia.
15652776 TNF-alpha inhibitors in systemic vasculitides and connective tissue diseases. 2005 Jan The introduction of TNF-alpha inhibitors in the treatment of rheumatoid arthritis and several other diseases meant a major progress in the management and to the understanding of these chronic inflammatory diseases. In this article, the evidence of the role of TNF-alpha and for TNF-alpha inhibitors in systemic vasculitides and connective tissue diseases is reviewed. TNF-alpha is expressed in inflammatory lesions. TNF-alpha acts as a proinflammatory cytokine in most disease processes analyzed so far, but it might have anti-inflammatory properties under certain conditions as well, e.g. with respect to B-cell regulation in systemic lupus erythematosus. It is not clear to what extent such aspects will be important in the treatment of connective tissue diseases and systemic vasculitides with TNF-alpha inhibitors. So far, most case reports and case series have suggested favourable results with TNF-alpha inhibitor therapy in systemic lupus erythematosus, dermato- and polymyositis, giant cell arteritis, Churg-Strauss syndrome, Wegener's granulomatosis and microscopic polyangiitis. Results of randomized, placebo-controlled trials are awaited for several connective tissue diseases and systemic vasculitides. One randomized, placebo-controlled trial has found no efficacy of infliximab treatment in primary Sjögren's syndrome recently.
17073673 The role of HLA promoters in autoimmunity. 2006 Population studies reveal HLA class I and class II gene polymorphisms associated with all the common chronic autoimmune diseases, notably spondylarthropathies, rheumatoid arthritis, multiple sclerosis and type I diabetes. We here discuss the exceptionally high levels of nucleotide diversity in the MHC region likely to reflect not only balancing selection acting on the epitope binding sites but also natural selection operating on the promoter region. The latter possibility is supported by functional studies with promoters, higher levels of diversity in the promoters of class II than class I genes and the relatively high frequency of single nucleotide polymorphisms around transcription factor binding sites. This, we argue, reflects the need for an appropriate level of signalling at the immunological synapse. We here summarise our knowledge of HLA promoter polymorphisms and how these translate into differential expression, T cell polarisation and inflammation. We discuss current strategies for pharmaceutical intervention in HLA expression.
21794326 [Complementary and alternative medicine in patients attending a rheumatology department fo 2006 Jul OBJECTIVES: To determine the frequency of the use of complementary and alternative medicine (CAM) in patients attending a rheumatology department in a general hospital for the first time. SUBJECTS AND METHODS: We included consecutive patients attending our rheumatology department for the first time. All the patients completed a self-administered questionnaire containing items on demographic data, and prior diagnosis. The patients were also given a list of 22 different CAM and marked those they had previously used. RESULTS: Eight hundred patients were studied. Eighty percent were women. The mean age was 44.8±14.9 years and the mean number of years of education was 7±4. The main diagnoses were osteoarthritis (29.4%), rheumatoid arthritis (22.3%), and fibromyalgia (6.5%). Seventy-one percent had previously used CAM, with a median of two (0-14) different types. The most common were vitamin supplements (38%), arnica (18%), Aloe vera (15%) and homeopathy (15%). No significant differences were found in sex, age, educational level, or diagnosis. The use of CAM was more frequent in patients with longer disease duration. CONCLUSIONS: The frequency of use of CAM is high in patient with rheumatologic manifestations.
15853742 Modulation of TNF receptor family members to inhibit autoimmune disease. 2005 Apr Certain members of the TNF-receptor family have shown proinflammatory function during immune activation and can be directly involved with the pathogenic effects observed during an autoimmune episode. The TNF-R family members summarized in this review includes: TNF-RI + II, OX40, and 4-1BB and they are expressed on a variety of leukocytes within the body. Studies within the last decade suggest that all of these proteins or their natural ligands can be targeted with various agents designed to diminish clinical signs of disease in autoimmune models. The data from the preclinical models specifically involving TNF-blockade have led to the development of clinical trials for patients with multiple sclerosis and rheumatoid arthritis. This review will chronicle the preclinical development of agents designed to inhibit OX40 and 4-1BB functions in autoimmunity and discuss relevant preclinical and clinical data associated with TNF-blockade.
15708534 Histone deacetylase inhibitors: new drugs for the treatment of inflammatory diseases? 2005 Feb 1 Histone deacetylase (HDAC) inhibitors induce cell cycle arrest and differentiation in cancer cells and have been in Phase I-II clinical trials for the treatment of various solid or haematological malignancies. In recent years, HDAC inhibitors have emerged as potent contenders for anti-inflammatory drugs, offering new lines of therapeutic intervention for rheumatoid arthritis or lupus erythematosus. The molecular mode of action of HDAC inhibitors is still controversial but seems to rely on reduced inflammatory mediator production, such as nitric oxide or cytokines, which implies inhibition of the transcription factor NF-kappaB. These anti-inflammatory effects will hopefully lead us to appreciate the complex anti-tumour effects of HDAC inhibitors.