Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
12168486 Introduction to some common cutaneous foot conditions and their management. 2002 Jul Problems that happen to the body through injury or disease can also happen to the owner's feet, and there are additional complications associated with the feet. Feet are a long way from the core, are in contact with an unclean environment (the ground), can be abused through poor-fitting footwear and are subjected to more general wear and tear than many other parts of the body. There are a large number of conditions affecting the feet, many associated with medical disorders such as diabetes, rheumatoid arthritis or peripheral vascular disease. The symptom of pain often triggers help being sought, but change in the appearance of the skin is a very important indicator of the state of superficial and deeper tissues. Health-care professionals may be called upon to comment on these conditions and treat and/or refer accordingly, so a multidisciplinary approach is required. Clinical skill is required to identify the conditions which are treatable, or those which should be referred for treatment by someone in another specialism. This paper provides information for clinicians and interested others in the form of an introduction to some common cutaneous foot conditions through outline case examples and their treatment.
12144523 Crystallization and preliminary x-ray studies of the Fab fragment from a humanized version 2002 Jun A humanized version of the apoptosis-inducing mouse anti-human Fas monoclonal antibody, HFE7A, is under further development for the treatment of autoimmune diseases such as rheumatoid arthritis. We have crystallized the antigen-binding fragment (Fab) of the humanized HFE7A. The crystals belong to the orthorhombic space group P2(1)2(1)2(1) with cell dimensions a = 54.4 A, b = 82.7 A, c = 104.9 A and contain one Fab molecule in the asymmetric unit. X-ray diffraction data were collected to 2.8 A resolution.
15126135 Morphological basis of sensory neuropathy and neuroimmunomodulation in minor salivary glan 2004 Jul OBJECTIVE: A predominance of sensory neuropathy was earlier described in Sjögren's syndrome (SS), which might precede the presence of sicca symptoms. The mechanism of sensory neuropathy in SS is unknown. Therefore, the aim of this study was to determine the quantitative changes of the different neuropeptide containing nerve terminals and the immunocompetent cells in labial salivary glands of primary SS. DESIGN: Immunohisto- and immunocytochemical methods were used for the detection of immunoreactive (IR) elements and the data were compared with the healthy controls. RESULTS: All of the investigated IR nerve fibres were found in different quantity and localisation in both of control and SS glands. The density of them was changed variously in SS. The number of the substance P (SP), neuropeptide Y (NPY) (P < 0.05), galanin (GAL) IR nerve terminals was decreased, however, the number of vasoactive intestinal polypeptide (VIP) and tyrosine beta-hydroxylase (TH) IR nerve fibres (P < 0.05) was increased compared to the control. There were no IR immunocompetent cells in the control materials, however, a large number of them showed IR for SP (46.2%) and NPY (34.4%) in the SS. The IR was demonstrated mainly in the mast cells, plasma cells and some of the lymphocytes. CONCLUSIONS: These neuropeptides might have a role in the sensory neuropathy; they might activate nociceptive and sympathetic pathways. Some neuropeptides (SP, NPY) are endogenous in the immune system and produced in certain conditions, e.g. inflammation and chronic autoimmune disorders such as SS, so they might participate in the neuroimmunomodulation and contribute to the atrophy, apoptosis and necrosis.
14991355 Paraneoplastic antibodies against HuD detected by a sensitive radiobinding assay. 2004 Feb Patients with paraneoplastic encephalomyelitis(subacute sensory neuronopathy) (PEM/SSN), most commonly associated with small-cell lung cancer (SCLC), frequently harbor Hu antibodies, which are usually detected by indirect immunohistochemistry or immunoblot. We developed a new radioimmunobinding assay to detect Hu antibodies based on in vitro transcribed and translated (ITT) HuD. High levels of Hu antibodies were detected in all seven PEM/SSN patients tested, but not in any of 15 patients with other paraneoplastic syndromes, 20 patients with Sjögren's syndrome, 20 patients with miscellaneous tumors and 99 of 100 blood donors. One of the blood donors had low levels of Hu antibodies. The radiobinding assay detected Hu antibodies in 45 of 191 (24%) patients with SCLC, in comparison with immunofluorescence and immuno dot blot, where only 34 of 191 (18%) were detected. All patients with Hu antibodies detected by immunofluorescence and immuno dot-blot were also positive by the radioimmunobinding assay. The results demonstrate that this assay is very specific and sensitive for the detection of Hu antibodies.
12792478 Tumor necrosis factor inhibitor gene expression suppresses lacrimal gland immunopathology 2003 May PURPOSE: To evaluate the effect of tumor necrosis factor (TNF) inhibitor protein on lacrimal gland immunopathology and ocular surface disease resulting from induced dacryoadenitis. METHODS: Autoimmune dacryoadenitis was induced in rabbits by injecting the lacrimal glands with peripheral blood lymphocytes (PBLs) activated by 5 days of coculture with autologous acinar cells in a mixed cell reaction. In the treated group, an adenoviral vector carrying the TNF inhibitor gene (AdTNFRp55-Ig) was concurrently injected with AMCR-PBL. Tear production was monitored by Schirmer test, and tears were collected for detection of TNF-inhibitor protein. Frozen sections of the glands were immunostained for expression of CD4, CD8, rabbit thymic lymphocyte antigen (RTLA), and CD18. Histological sections of lacrimal glands were examined using the TUNEL technique to monitor apoptosis. RESULTS: Soluble TNF-inhibitor protein was detected by ELISA in tears, with titers at a maximum on day 3, declining by day 7, and undetectable by day 14. Tear production declined in the induced dacryoadenitis group but did not change when glands had been treated with AdTNFRp55-Ig simultaneously with disease induction. Tear break-up time and rose bengal staining properties were not altered by treatment. Fourteen days after the glands were injected with activated PBLs, focal mononuclear cell infiltrates were observed around ducts and venules, some of which assumed the high endothelial phenotype, and between acini. Immune cells in the infiltrates stained positive for CD4, RTLA, and CD18. Glands that received AdTNFRp55-Ig concurrently with activated PBLs had decreased numbers of CD4 cells, CD18 cells, RTLA, and apoptotic cells. CONCLUSIONS: In vivo transduction of the lacrimal gland with AdTNFRIp55-Ig resulted in transient expression in the gland and the appearance of TNF-inhibitor protein in tears. The presence of soluble TNF-inhibitor protein partially suppressed the appearance of Sjögren's syndrome-like features of reduced tear production and the immunohistopathology associated with induced autoimmune dacryoadenitis but not tear break-up time and ocular surface disease. This may reflect immunoregulation in the lacrimal gland but not in the conjunctiva.
12827398 [Treatment of primary systemic vasculitis with TNF alpha-antagonists]. 2003 Jun After the introduction of the TNF alpha blocking drugs Etanercept and Infliximab for the standard therapy of rheumatoid arthritis these effective substances have also been used successfully in many patients with primary systemic vasculitides, who were unresponsive to standard therapy. From pathophysiologic findings their use is justified by the prominent role of TNF alpha in the inflammation of small and large vessels. So far only open studies with a maximum of 20 patients and case reports are published. In summary there are reports of the successful treatment of 7 patients with rheumatoid vasculitis, 39 patients with Wegener's granulomatosis, 3 patients each with microscopic Polyangiitis, and 5 patients each with temporal Arteritis or Takayasu disease with Etanercept as well as with Infliximab. In addition, Infliximab was also used with a good response in severe Polymyalgia rheumatica in 4 cases and in one case of a cryoglobulinemic vasculitis. More than 60 patients with Panuveitis and other manifestations of Behçet's disease were treated with Infliximab or Etanercept according to preliminary reports. Because of the overall positive reports with TNF alpha collected in this review controlled investigations for their use in primary systemic vasculitis are necessary.
17143658 Efficacy and safety of the anti-TNF biologic agents. 2004 The last decade has seen a marked increase in the elucidation of cellular and molecular factors involved in chronic inflammatory processes that contribute to the pathogenesis of rheumatoid arthritis (RA). Multiple lines of evidence have demonstrated a critical role for the proinflammatory cytokine tumor necrosis factor (TNF) in the perpetuation of inflammatory synovitis and the subsequent destruction of cartilage and bone that leads to the functional disability observed in RA. In the light of these discoveries, new therapeutics have been developed to target TNF. The consistent efficacy demonstrated by these agents for the treatment of RA has validated TNF as an important mediator of the chronic inflammatory events and structural damage that occur with the disease. Three of these agents (etanercept, infliximab, and adalimumab) have been approved by the United States Food and Drug Administration (FDA) over the last 5 years for treatment of moderately to severely active RA. This article will first explain the role of TNF in inflammation and RA, and then compare and contrast the mechanisms of action, efficacy, and safety profiles of the various FDA-approved TNF inhibitors, as well as offer potential explanations for the clinical differences observed between these agents, especially with regard to safety.
17041402 Coexistence of four autoimmune diseases in one patient: the kaleidoscope of autoimmunity. 2002 Dec Genetic, immune, hormonal, and environmental factors are associated with the multifactorial origin of autoimmunity. When one or more of these factors are altered, a "switch" from one autoimmune condition to another can occur, developing the so called "kaleidoscope phenomenon" of autoimmunity. We present the case of a 30-year-old woman with myasthenia gravis and hypothyroidism probably resulting from autoimmune thyroiditis. A thymectomy was performed, and 1 year later, rheumatoid arthritis was diagnosed based on clinical, radiological, and serological features. Nine years after thymectomy, systemic lupus erythematosus was diagnosed based on skin, renal, hematologic, and immunologic manifestations. We suggest that the immune system function was modified when thymectomy was performed, playing an important role in the development of the new autoimmune conditions. Thymectomy increases the risk of developing a new autoimmune disease because it modifies, by mechanisms not well defined, the equilibrium and normal function of the immune system. This patient presents the infrequent association of four autoimmune conditions. When a patient has one autoimmune disease, she is at risk for another.
15648824 Fish oil and inflammatory disease: is asthma the next target for n-3 fatty acid supplement 2004 Dec Eating fish or taking n-3 fatty acid supplements can decrease the risk and severity of cardiovascular disease. Such supplements also provide symptomatic relief for rheumatoid arthritis patients. Recent research suggests that asthma, another highly prevalent, chronic inflammatory disease, may also respond to fish oil supplements.
15560982 Tumour necrosis factor alpha as a therapeutic target for immune-mediated inflammatory dise 2004 Dec Preclinical studies have identified and validated tumour necrosis factor alpha (TNFalpha) as a key disease molecule and therapeutic target for immunotherapeutic intervention in many immune-mediated inflammatory diseases. Clinical indications include rheumatoid arthritis, Crohn's disease, ankylosing spondylitis and psoriasis. Recent clinical findings indicate that many chronic inflammatory disorders share certain pathogenic pathways, whereas others are limited to particular disease phenotypes. Better understanding of these pathogenic pathways will inform the development of new therapeutic approaches leading to more complete and sustained disease remissions.
15507049 Support network of adolescents with chronic disease: adolescents' perspective. 2004 Dec The purpose of this study was to describe the support network of adolescents with a chronic disease from their own perspective. Data were collected by interviewing adolescents with asthma, epilepsy, juvenile rheumatoid arthritis (JRA) and insulin-dependent diabetes mellitus (IDDM). The sample consisted of 40 adolescents aged between 13 and 17 years. Interview data were examined using content analysis. Six main categories were established to describe the support network of adolescents with a chronic disease: parents, peers, school, health care providers, technology and pets. Peers were divided into two groups: fellow sufferers and peers without a chronic disease. At school, teachers, school nurses and classmates were part of the support network. Health care providers included nurses, physicians and physiotherapists. Technology was also part of the support network and included four techniques that may be used to communicate: computers, mobile telephones, television and videos. The results provided a useful insight into the social network of adolescents with chronic disease and serve to raise awareness of the problems and opinions experienced by adolescents with this condition.
15469405 Pharmacogenetics of methotrexate. 2004 Oct Methotrexate (MTX) has proven efficient in the treatment of a number of malignancies, as well as non-malignant disorders characterized by a rapid cellular growth. Yet some patients might develop resistance, while others could have toxic side effects. MTX achieves its cytotoxicity through the inhibition of folate-dependent enzymes, suggesting that the genes controlling their activity or the levels of folate cofactors can modulate drug efficacy and, thus, the sensitivity of a patient to MTX. Indeed, several studies, conducted mostly in leukemia and rheumatoid arthritis patients, have addressed the potential for tailoring MTX therapy based on a patient's genetics. Several genetic variants have been shown to have a predictive role, among which the most frequently studied are those of methylenetetrahydrofolate reductase and thymidylate synthase genes. The other candidates, as well as gene-gene interactions, which may be even more important for the prediction of disease outcomes than the individual gene effects, are also briefly discussed.
15379671 The NF-kappaB pathway as a potential target for autoimmune disease therapy. 2004 A battery of proinflammatory agents triggers the activation of NF-kappaB. This inducible transcription factor participates in the expression of an exceptionally large number of target genes, many of them contributing to the regulation of innate and adaptive immunity. Since some target genes also function as NF-kappaB activators, activation of this transcription factor allows the establishment of a signal amplification loop. Dysregulation of the NF-kappaB system and hyperactivated expression of inflammatory mediators are often found in association with some autoimmune diseases, which occur upon mounting of the adaptive immune response against self-antigens. In this review we summarize the relevance of aberrant NF-kappaB signaling for the development and perpetuation of some autoimmune diseases such as rheumatoid arthritis, diabetes mellitus type 1 and Crohn's disease. The assets and drawbacks of systemic or cell-type specific NF-kappaB inhibitors and their potential use in therapy of autoimmune diseases are critically discussed.
12926662 Establishment of the International Assessment Committee of Bone and Joint Diseases. 2003 Aug During the International Conference of the Bone and Joint Decade, held in Tokyo in April 2002, the International Assessment Committee of Bone and Joint Diseases was established. This committee is responsible for data collection, effective prevention and treatment, supply of care provisions, costs and priorities, and measurement to determine the outcome of patients with bone and joint diseases. Study planning was initiated by the Japanese Committee of Assessment, in cooperation with the Bone and Joint Monitor Project conducted by Prof. Anthony Woolf. As a result of our studies, we expect to obtain data concerning international comparisons of incidence, prevalence, and impact, as well as secular trends regarding the burden of musculoskeletal conditions, risk factors, and outcomes of each condition. Described here are results of population-based studies regarding the prevalence of rheumatoid arthritis (RA), osteoarthritis, osteoporosis, and limb fractures in Japan compared with those in Western countries, as well as a comparison of secular trends of RA incidence between Japanese and European subjects.
12768326 Stabilization of the ulna stump after Darrach's procedure at the wrist. 2003 We studied the outcome of patients with chronic distal radioulnar joint symptoms who were treated with excision of the distal ulna and reconstruction using the flexor carpi ulnaris tendon. Twelve patients with 14 wrists were assessed. Ten patients were posttraumatic, and two had bilateral surgery for rheumatoid arthritis. Average age was 37 years at time of operation. Follow-up averaged 20 months (9 months to 4 years). All patients except one reported improvement in pain symptoms. Grip strength of the operated hand as measured by dynamometer readings was 67% of the strength of the normal hand with five wrists achieving an excellent result in grip strength. Eleven patients reported a subjective improvement in functional activities. An improved range of motion was obtained in all patients. We discuss the importance and basis for ligamentous reconstruction following excision of the distal ulna and review the literature for other previously described procedures.
12705782 Contraindications to the Dix-Hallpike manoeuvre: a multidisciplinary review. 2003 Apr The Dix-Hallpike manoeuvre is widely used in the diagnosis of positional vertigo and is regarded as safe. The manoeuvre involves a degree of neck rotation and extension, and consequently one might expect there to be some patients, particularly those with neck problems, in whom the manoeuvre is contraindicated. The term 'neck problem', however, encompasses a whole range of conditions, including soft tissue disorders, cervical spondylosis, prolapsed intervertebral disk, and severe rheumatoid arthritis with cervical instability. These in turn will give rise to a variety of symptoms, which will vary from minimal pain or stiffness to severe pain or complete immobility, and, in some cases, neurological deficit. Clarification is therefore needed to establish the point at which any neck pain or stiffness ceases to be a minor problem and becomes a contraindication to performing the Dix-Hallpike manoeuvre. This paper clarifies this issue by discussing the issue of absolute contraindications and proposing a simple functional assessment of neck mobility which can be performed prior to performing the Dix-Hallpike manoeuvre. Relative contraindications such as back pathology, vertebrobasilar ischaemia (posterior circulation ischaemic disease), nerve root compression and medical fitness are also discussed.
12514498 Skin changes in the "at risk" foot and their treatment. 2002 Dec The skin provides a "mirror" of the patient's general health, and any changes from normal for that person may be generalized or located to specific body sites. In the foot, poor quality skin may develop associated with a number of medical disorders such as diabetes or rheumatoid arthritis, and peripheral states such as peripheral vascular disease. In these instances the foot is "at risk" of developing ulcers following even minor trauma. To manage epidermal and dermal changes efficiently, it helps to have a good understanding of the skin structure and function as well as knowledge of the more common conditions affecting the poorly viable foot. Skin physical characteristics change in the "at risk" foot and skin conditions and lesions, e.g. anhydrosis, fissures, ulceration, can develop readily and left untreated, there is increased morbidity and risk of mortality. Even apparently minor skin conditions in the foot are therefore worthy of attention and appropriate treatment as introduced in this paper, as all those involved in health care have a responsibility and role in foot health education.
12192201 Thyroid-related autoantibodies and celiac disease: a role for a gluten-free diet? 2002 Sep An association between celiac disease and other autoimmune disorders--such as insulin-dependent diabetes, Addison's disease, systemic lupus erythematous, rheumatoid arthritis, alopecia areata, and autoimmune endocrine diseases--has been described. The aim of this study was to evaluate the prevalence of celiac disease in 100 patients with autoimmune thyroid disease. Moreover, the monitoring of patients with concomitant celiac and autoimmune thyroid diseases, after a gluten-free diet or a gluten-containing diet, can give important insights into the effect of dietary habits in thyroid autoantibodies modulation. In our study, the prevalence of celiac disease in patients with autoimmune thyroid disease was 2%. In these two celiac patients, the serologic markers became undetectable 6 months after beginning a gluten-free diet. However, thyroid autoantibodies did not positively correlate with dietary habits.
12109294 [New approaches to prognosis of risk of development of gastropathies induced by nonsteroid 2002 Mar A pharmacological test with indomethacin is suggested for predicting the risk of NSAID-induced gastropathy. It is shown that patients with diagnoses of rheumatoid arthritis and osteoarthrosis can be divided into two groups with respect to the indomethacin test--"vulnerable" and "resistant", characterized by a high and low risk of NAIDS-induced gastropathy development, respectively. The proposed index of resistance to this disorder, together with the glutathione redox buffer test index, can be used as reliable criteria for predicting the NSAID-induced gastropathy.
11892715 Intralesional therapy in carpal tunnel syndrome: a sonographic-guided approach. 2002 Jan OBJECTIVE: The aim of this pictorial essay is to show a representative example of sonographic-guided injection in carpal tunnel syndrome associated with tenosynovitis of the finger flexor tendons. METHODS: Images were obtained using a real-time ultrasound system (AU4-idea; Esaote Biomedica, Genoa, Italy) equipped with a 13-MHz linear transducer. The best injection site was detected using a fine metal clip placed between the skin and the transducer. The images here were obtained in a patient with rheumatoid arthritis and carpal tunnel syndrome secondary to tenosynovitis of the finger flexor tendons. RESULTS: Steroid injection within the carpal tunnel under sonographic control was easily performed. All steps of the needle placement within the widened tendon sheath were carefully evaluated on the monitor screen. Marked clinical improvement occurred shortly thereafter (3 days) and increased over the next 6 weeks. CONCLUSION: A detailed assessment of the carpal tunnel and a correct, safe placement of the needle for steroid injection can be quickly performed under sonographic guidance.