Browse

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

ID PMID Title PublicationDate abstract
18277540 [Contents of antibodies to Bordetella pertussis antigens in patients with rheumatic diseas 2007 Nov Study of presence of antibodies against pertussis in 72 rheumatic patients (with uvenile rheumatoid arthritis, systemic lupus erythematosus, etc.) aged 1-18 year old without history of pertussis was performed. Mean age of the patients was 10.6 +/- 0.48 year old, duration of illness--51.2 +/- 4.42 months. Immunosupressive therapy at the time of the study was conducted in 68 (94.4%) children. Using ELISA method, IgG to pertussis toxin (PT) and to antigens of acellular pertussis vaccine (aPV) were detected in 98.6% and 100% of children. High titers of antibodies were detected more frequently in 7-18 year old age group, which can indicate recent pertussis disease or infection. Vaccination history was studied in 131 children with rheumatic diseases. Incidence of pertussis in 43 unvaccinated children was 116.3 per 1000, and in 16 children with incomplete vaccination--62.5 per 1000. Out of 75 patients, who received vaccination series and revaccination, clinically distinct pertussis was not diagnosed.
18180563 [Isolated tuberculous tenosynovitis of the Achilles tendon: a report of two cases]. 2007 Aug Tuberculous tenosynovitis involving the tendons of the feet is very rare. Isolated primary tuberculous tenosynovitis of the Achilles tendon was detected in two women aged 19 and 53 years, respectively. The younger patient had a swollen and painful Achilles tendon in the left foot. Complete excision of the lesion followed by antituberculous chemotherapy for six months resulted in complete improvement. Magnetic resonance imaging showed normal findings at the end of six months and no recurrence after 27 months of follow-up. The older patient had diabetes and was on cytostatic treatment for rheumatoid arthritis. She had difficulty in squatting and climbing stairs due to swelling and pain in the right ankle. She underwent abscess drainage and excision of the cystic mass. Despite disappearance of symptoms in the affected ankle in the course of antituberculous chemotherapy, she died due to miliary tuberculosis in the sixth month. Tuberculous tenosynovitis should be considered in the differential diagnosis of patients suffering from persistent swelling and pain in the hind foot.
18096055 The views of stakeholders on controlled access schemes for high-cost antirheumatic biologi 2007 Dec 20 BACKGROUND: In Australia, government-subsidised access to high-cost medicines is "targeted" to particular sub-sets of patients under the Pharmaceutical Benefits Scheme to achieve cost-effective use. In order to determine how this access system could be improved, the opinions of key stakeholders on access to biological agents for rheumatoid arthritis were explored. METHODS: Thirty-six semi-structured interviews were conducted with persons from relevant stakeholder groups. These were transcribed verbatim, and analysed thematically. RESULTS: Controlled access to expensive medicines was considered to be equitable and practical; however, there was disagreement as to the method of defining the target patient populations. Other concerns included timeliness of access, excessive bureaucracy, and the need for additional resources to facilitate the scheme. Collaboration between stakeholders was deemed important because it allows more equitable distribution of limited resources. The majority considered that stakeholder consultation should have been broader. Most wanted increased transparency of the decision-making process, ongoing and timely review of access criteria, and an increased provision of information for patients. More structured communication between stakeholders was proposed. CONCLUSION: The Pharmaceutical Benefit Scheme is adapting to meet the changing needs of patients. Provision of subsidised access to high-cost medicines in a manner that is affordable for individuals and society, and that is equitable and efficiently managed is challenging. The views of stakeholders on targeted access to anti-rheumatic biological medicines in Australia acknowledged this challenge and provided a number of suggestions for modifications. These could serve as a basis to inform the debate on how to change the processes and policies so as to improve the scheme.
18068874 [Management of cytomegalovirus infections in patients treated with immunosuppressive drugs 2008 Apr INTRODUCTION: For patients with chronic inflammatory disease treated by immunosuppressive agents (for example: rheumatoid arthritis or systemic lupus erythematosus), there are no available guidelines in medical literature on the use of antiviral agents for the management of symptomatic cytomegalovirus (CMV) infection. EXEGESIS: A patient treated by methotrexate for a spondylarthritis presented a CMV infection manifested with persistent fever and pneumonia. CMV pp65 antigenemia was of 120 positive nuclei for 100,000 cells. Treatment with valganciclovir allowed a prompt recovery, while treatment by methotrexate was maintained. CONCLUSION: Symptomatic CMV infection evolution is unpredictable and potentially severe in patients with chronic inflammatory diseases receiving immunosuppressive agents. Although there is no data issued from clinical trials, the observation reported in this article and the publications of similar cases in the medical literature indicate that treatment with valganciclovir seems worth to be used in this context. Stopping immunosuppressive therapy does not seem mandatory.
17897077 Selective glucocorticoid receptor ligands. 2007 Sep Glucocorticoids are four-ring steroid compounds that regulate a wide range of physiological systems ranging from embryonic respiratory development, immune function and responses to acute or chronic stress. Glucocorticoids are taken up by many target cells where they bind and activate cytoplasmic glucocorticoid receptors (GRs), which then dimerize, translocate to the nucleus and function as ligand-dependent transcriptional regulators. Synthetic glucocorticoids such as dexamethasone and prednisolone have for decades been the cornerstone for the clinical treatment of inflammatory diseases, such as rheumatoid arthritis and asthma, yet prolonged use have undesirable side-effects such as persistent immune suppression, metabolic imbalance, obesity, diabetes, and osteoporosis. Detailed understanding of the cell signaling mechanisms of GR action has led to the development of novel selective glucocorticoid receptor ligands that appear to offer more efficient treatments for a number of diseases while eliciting fewer side-effects. Additionally, in cell-based and animal model systems a number of compounds such as the methane sulphonamides and a novel compound A-348441 have shown promise as GR antagonists. Other classes of ligands such as the benzopyranoquinolines and the arylpyrazoles have further been shown to selectively influence the transcriptional regulatory properties of GRs on different target gene in various cellular contexts. These selective GR modulators are believed to initiate transcriptional co-regulator recruitment that in turn promotes specific gene responses relevant to the more efficient and specific treatment of inflammatory conditions and metabolic diseases such as type-2 diabetes.
17571244 [Renal manifestations in rheumatic diseases]. 2007 Aug Inflammatory rheumatic diseases other than systemic vasculitides and systemic lupus erythematosus are frequently associated with renal abnormalities, which are clinically less apparent due to the subtle course and the often only moderate impairment of renal function. These abnormalities include vascular, glomerular and tubulointerstitial changes. Renal manifestations in the course of rheumatoid arthritis influence the prognosis of the disease. Renal involvement due to AA amyloidosis following long-standing inflammatory joint disease can lead slowly, over years, to end-stage renal disease. A scleroderma renal crisis in the course of systemic sclerosis can potentially result in end-stage renal disease within days. The differential diagnosis of renal abnormalities in a rheumatic patient should include drug induced renal impairment as well as infection.
17133319 [A special case of thyroid associated ophthalmopathy in the course of Graves-Basedow disea 2006 Sep INTRODUCTION: The exact pathogenesis of Graves' ophthalmopathy and the possibility of causal treatment of this disease still remain unclear. Currently no standard treatment guidelines have been accepted. While treatment procedures have been established in specialized centres, management of complicated and long-lasting cases is always individual. We present an unusual case of Graves' ophthalmopathy accompanied by other autoimmune diseases. CASE REPORT: Our patient, MB, female, born in 1961, was diagnosed with Graves' disease 13 years ago. Recurrent hyperthyroidism and large goitre qualified her for strumectomy (performed twice) and long-term antithyroid treatment. Four years after her initial diagnosis, relapsing severe (ophthalmopathy index: 9 points, CAS: 7 points) occurred which persisted despite continuous administration of glucocorticoids. Due to imminent blindness, orbital decompression had to be performed, three times since. Concurrent autoimmune diseases: ulcerative colitis and seronegative rheumatoid arthritis were also stated. Two years ago, due to loss of vision acuity, rapid progression of exophthalmos and recurrence of hyperthyroidism, immunosuppressive treatment with azathioprine was undertaken over a period of 12 months. The present condition of the patient is satisfactory. CONCLUSION: Judging from the discussed course of treatment, in rare and difficult cases of proliferative ophthalmopathy, early immunosuppressive treatment other than glucocorticoids, should be considered.
17064039 Synthesis of a naphthyridone p38 MAP kinase inhibitor. 2006 Oct 27 Compound 1 is a p38 MAP kinase inhibitor potentially useful for the treatment of rheumatoid arthritis and psoriasis. A novel six-step synthesis suitable for large-scale preparation was developed in support of a drug development program at Merck Research Laboratories. The key steps include a tandem Heck-lactamization, N-oxidation, and a highly chemoselective Grignard addition of 4-(N-tert-butylpiperidinyl)magnesium chloride to a naphthyridone N-oxide. The N-oxide exerted complete chemoselectivity via chelation in directing the Grignard addition to the alpha position as opposed to 1,4-addition on the ene-lactam. The dihydropyridyl adduct was in situ aromatized with isobutylchloroformate followed by heating in pyridine. Syntheses of Grignard precursor, N-tert-butyl-4-chloro-piperidine, were accomplished via transamination with a quaternary ammonium piperidone or via addition of methylmagnesium chloride to an iminium ion. Utilizing this chemistry, multi-kilogram preparation of compound 1 was successfully demonstrated.
17047110 The role of the sympathetic nervous system in intestinal inflammation. 2006 Nov The nervous system in the intestine controls motility, secretion, sensory perception, and immune function. Peptidergic neurones with neurotransmitters such as substance P and nerve growth factors have been the main focus of neuroimmunomodulation research in the gut. This review summarises the present knowledge concerning the role of the sympathetic nervous system (SNS) in modulating intestinal inflammation. The role of the SNS for gut inflammation is compared with its role in rheumatoid arthritis which demonstrates notable similarities. Nerve fibres of the SNS not only enter the enteric plexuses but also innervate the mucosa and gut associated lymphoid tissue (GALT). The SNS has pro- and anti-inflammatory functions. Neurotransmitters such as norepinephrine, adenosine, and others can evoke remarkably different opposing effects depending on concentration (presence of sympathetic nerve fibres and extent of neurotransmitter release), receptor affinity at different receptor subtypes, expression of adrenoceptors, availability of cotransmitters, and timing of SNS activity in relation to the inflammatory course. This review attempts to integrate the different perspectives of the pro- and anti-inflammatory effects of the SNS on inflammatory disease of the gut.
16901030 The early history of giant cell arteritis and polymyalgia rheumatica: first descriptions t 2006 Aug Giant cell arteritis and polymyalgia rheumatica were described separately more than 100 years ago. However, the original reports of both conditions were neglected for many years. After the article by Horton et al on giant cell arteritis in the 1930s and studies published by others in the 1940s, giant cell arteritis began to be recognized as a specific disease. In the 1950s and 1960s, many of the numerous presentations and complications of giant cell arteritis were recorded. In a somewhat similar fashion, physicians became cognizant of polymyalgia rheumatica only after several independent descriptions in the 1940s and 1950s. The rapid response of both syndromes to glucocorticoid therapy was discovered shortly after cortisone's effect on rheumatoid arthritis was described. The origin of the proximal aching and stiffness in polymyalgia rheumatica was more difficult to understand. The relatively minor findings in the joints on physical examination seemed insufficient to account for the severe discomfort. As the link between polymyalgia rheumatica and giant cell arteritis became apparent, some thought the aching in polymyalgia rheumatica was related to vasculitis. The debate about whether proximal synovitis or vasculitis was the cause of the symptoms continued after 1970. Although the reason these 2 conditions were associated was not considered by 1970, the establishment of the syndromes as clinically linked entities provided the groundwork for further progress in the next decades.
16855160 Predicting and preventing autoimmunity, myth or reality? 2006 Jun Many autoimmune diseases are chronic conditions that progress over the course of years, and are characterized by the presence of autoantibodies that precede the overt disease by months or years. As examples, the presence of two islet cell antibodies (ICA) are associated with a 50% risk of developing diabetes mellitus in 5 years, anticyclic citrullinated (anti-CCP) antibodies are found in the sera of rheumatoid arthritis (RA) patients a median of 4.5 years before the overt disease, and in systemic lupus erythematosus (SLE), patients accrue antibodies throughout a foreseen course during the 3-4 years prior to the clinical symptoms. This ability to predict autoimmune diseases, or rather their clinical manifestations, leads to the prospect of screening healthy individuals for autoantibodies. The importance of such a notion lies not only in the ability to prevent life-threatening manifestations, such as Addisonian's crisis and thyroid storm, but also in the ability to treat and even prevent overt autoimmune diseases. Among such documented treatment modalities are administration of aspirin in antiphospholipid syndrome, ursodeoxycholic acid in primary biliary cirrhosis (PBC), vitamin D in SLE and autoimmune thyroid diseases (AITD), and more. Although additional studies are still needed to fully assess these notions, as well as the appropriate screening strategies to apply them, one cannot ignore the prospect of predicting and preventing autoimmunity.
16771071 Importance of lipids in the nutritional treatment of inflammatory diseases. 2006 May Over the last decades, scientific advances in the knowledge of anti-inflammatory properties of lipids have lead to the development of new formulas for enteral and parenteral nutrition. These products have been utilised as a treatment for a variety of inflammatory diseases. In this review we expose the effects of lipids used in enteral nutriton on different inflammatory pathologies such as inflammatory bowel disease, atherosclerosis, lung fibrosis, rheumatoid arthritis, and others. During inflammatory diseases, eicosanoids are produced from polyunsaturated fatty acids present in cellular membranes. Inflammatory activity of these molecules depends on the nature of their precursors: when arachidonic acid (n-6) is present, pro-inflammatory molecules are released, whereas eicosapentaenoic acid (n-3)-derived eicosanoids are weakly inflammatory. In this way, fish oils, rich in n-3 polyunsaturated fatty acids, increase the content of eicosapentaenoic-eicosanoids and decrease arachidonic acid in immune and endothelial cells leading to a lower inflammatory activity. Likewise, oleic acid exhibits anti-inflammatory effects by preventing the release of particular chemotactic molecules. In summary, enteral diets supplemented with n-3 polyunsaturated fatty acids and oleic acid benefits the treatment of patients with inflammatory pathologies, leading to better outcomes, and decreasing the doses of anti-inflammatory drugs, which exhibit important secondary effects.
16433597 Infliximab for chronic obstructive pulmonary disease: towards a more specific inflammation 2006 Feb Chronic obstructive pulmonary disease (COPD) is a predominantly smoking-related condition in which chronic progressive airways obstruction results because of inflammation that is triggered and maintained by the causative agent and enhanced during exacerbations. Inflammation is dominated by neutrophils, and macrophages and their mediators. TNF-alpha is a proinflammatory cytokine involved in COPD pathogenesis. Treatment of the stable disease is mainly inhalatory with anticholinergics, beta(2) agonsists and inhaled corticosteroids being involved in various stages of the disease. Novel therapeutic agents are currently under investigation for COPD treatment and some of them target various inflammation mediators. Infliximab is a monoclonal anti-TNF-alpha antibody with demonstrated efficacy in other autoimmune diseases, such as Crohn's disease and rheumatoid arthritis. The current study assesses the scientific rationale for the use of infliximab in COPD patients.
19210883 Drug-induced lupus-like syndrome in ankylosing spondylitis treated with infliximab. 2008 Nov Specific antagonists of tumour necrosis factor (TNF-alpha) have rapidly gained popularity for the treatment of rheumatoid arthritis and ankylosing spondylitis (AS). Reported side effects from these agents include drug-induced autoimmune disorders. The monoclonal antibody against TNF-alpha, infliximab, has been associated with induction of systemic lupus erythematosus (SLE) in only one patient with AS in the literature. However, there have been no published reports of drug induced lupus-like syndrome (LLS) with positive anti-histone antibodies. We describe a 59-year-old woman with a 12-year history of refractory axial AS who developed signs and symptoms of LLS during treatment with infliximb with positive antinuclear and anti-histone antibodies. On diagnosis of LLS, infliximab was discontinued and the LLS-related symptoms promptly resolved.
19143253 [Analyse of the risk factors of DVT after lower extremity surgery]. 2008 Nov OBJECTIVES: To investigate the morbility rate of deep venous thrombosis (DVT) after lower extremity surgery and analyze the risk factors. METHODS: All 136 cases of lower extremity surgeries in the period of Nov. 1999 to May. 2002 without any anti-coagulopathy agents pre-surgery were analyzed. There were 78 male and 58 female, aged from 16 to 82 years with an average age of 49.5 years. All the cases were examined by sonography before the surgery to rule out bilateral deep venous thrombosis, and were examined bilateral lower extremities with inverse phlebography postoperation, and finally the results were used to analyze the risk factors of DVT. RESULTS: DVT was found 24 in 51 arthroplastic patients, include 10 after THA and 14 after TKA, respectively. And the morbility rate of DVT after the surgical treatment of osteoarthritis, rheumatoid arthritis, femoral head aseptic necrosis and femoral neck fracture were 9, 6, 7, 12, respectively. CONCLUSION: Patients of aged, DVT history, cardiorespiratory compromises or diabetes mellitus, and using tourniquet or bone cement during the surgery are more likely to suffer from DVT after surgery.
19050416 Reversible encephalopathy due to sulfasalazine. 2008 Nov BACKGROUND: Sulfasalazine was devised by Swedish physician in the late 1930s in an attempt to treat "rheumatic polyarthritis." It is still a widely used anti-inflammatory agent especially in the treatment of rheumatologic disorders and inflammatory bowel diseases. Most of its side effects are benign, tolerable, and dose dependent, but less common severe systemic reactions have also been revealed. CASE PRESENTATION: A 42-year-old woman diagnosed with rheumatoid arthritis was admitted to emergency service because of status epilepticus. Hepatitis and myelotoxicity were also present after laboratory investigations. The patient was on sulfasalazine treatment for 3 weeks with a daily dose of 2g. Cranial magnetic resonance imaging (MRI) revealed bilateral periventricular and subcortical lesions in the white matter of especially temporal and occipital regions. Cerebrospinal fluid (CSF) examination showed very high protein level (564 mg/L). After discontinuation of treatment, the clinical, CSF, and MRI findings regressed rapidly. CONCLUSIONS: Side effects of sulfasalazine include neurotoxicity such as status epilepticus, cranial MRI lesions, and CSF abnormalities that were diagnosed in our patient after excluding other etiologic factors causing encephalitis.
18827055 Genomics and proteomics: a new approach for assessing thrombotic risk in autoimmune diseas 2008 Oct Several systemic autoimmune conditions, including rheumatoid arthritis, systemic lupus erythematosus and antiphospholipid syndrome, are characterised by enhanced atherosclerosis and, consequently, higher cardiovascular morbidity and mortality rates. The association of these diseases with atherosclerosis suggests a common pathogenic mechanism. Genomic and proteomic studies performed on atherosclerotic plaques have further confirmed the presence of a gene and protein profile similar to that observed in autoimmune diseases with cardiovascular risks. Human sera and body fluids have been analysed and have resulted in the identification of auto-antibodies that can be used as diagnostic markers in specific autoimmune diseases, and proteomic fingerprints of blood cells, tissues and body fluids have resulted in the identification of individual proteins or patterns of protein expression that are deregulated. The information provided by these proteomic studies is of diagnostic and therapeutic potential. In this review, we discuss new approaches available for assessing thrombotic risk in autoimmune diseases, focusing in the genomic and proteomic methods now available to deep into the origin of the mechanisms associated with vascular involvement in systemic autoimmune diseases. The increasing data available suggests that when treating patients with these autoimmune disorders, paying attention to the increased risk of cardiovascular disease is essential.
18825392 [Using the International Classification of Functioning, Disability, and Health in rheumato 2008 Nov The International Classification of Functioning, Disability, and Health (ICF) created by the World Health Organization provides both a framework and a classification comprehensively covering domains of function and disability in rheumatologic patients. The ICF can be used as a universal language understood by medical doctors, health professionals, researchers, patients, and other groups. It is based on an integrative biopsychosocial model of functioning. For its implementation in rheumatology and medicine in general, practical ICF-based tools such as the ICF Core Sets are necessary. These Sets, which were developed in a standardized scientific process, consist of the ICF categories that are most relevant for a specific group of patients, e.g. chronic patients with rheumatoid arthritis. In rheumatologic rehabilitation, patient problems, medical findings, treatment goals, and treatment concepts can be structured by applying the ICF, ICF Core Sets, and an ICF assessment sheet to patients. In outcomes research, ICF Core Sets can support the selection of relevant outcome domains.
18651052 [Role of omega-3 polyunsaturated fatty acids in diet of patients with rheumatic diseases]. 2008 Apr The beneficial effects of omega-3 polyunsaturated fatty acids have been widely described in the literature in particular those on cardiovascular system. In the last decade there has been an increased interest in the role of these nutrients in the reduction of articular inflammation as well as in the improvement of clinical symptoms in subjects affected by rheumatic diseases, in particular rheumatoid arthritis (RA). Nutritional supplementation with omega-3 may represent an additional therapy to the traditional pharmacological treatment due to the anti-inflammatory properties which characterize this class of lipids: production of alternative eicosanoids, reduction of inflammatory cytokines, reduction of T-lymphocytes activation, reduction of catabolic enzymes activity. The encouraging results of dietetic therapy based on omega-3 in RA are leading researchers to test their effectiveness on patients with other rheumatic conditions such as systemic lupus erythematosus and ankylosing spondylitis. Nutritional therapy based on food rich in omega-3 or on supplementation with fish oil capsules, proved to be a valid support to he treatment of chronic inflammatory rheumatic diseases.
18466601 Comparison of genome-wide single-nucleotide polymorphism linkage analyses in Caucasian and 2007 We performed linkage analysis on families with rheumatoid arthritis, stratifying by ethnic origin. We compared results using either Kong and Cox nonparametric LOD scores or MOD score analysis using the software GeneHunter MODSCORE. We first applied SNPLINK to remove markers showing excess linkage disequilibrium from the SNPs in the Illumina IV SNP Linkage panel. In this analysis there were 659 self-reported Caucasian families and 29 self-reported Hispanic families in the NARAC collection. Chromosome 19 yielded MOD scores > 3.00 in the Hispanic group, while chromosomes 2, 6, 7, 11, and XY had MOD scores > 3.00 in the Caucasian group. We performed simulation studies to evaluate the empirical distribution of the MOD score for autosomal loci separately in Hispanics and Caucasians. Results showed genome-wide significant evidence for linkage in Caucasians for chromosomes 2q and 6p, but no significant evidence for any linkages in the Hispanics, including little evidence for linkage to chromosome 6p in this group. An examination of the difference of phenotypes in two ethnic groups suggested significantly earlier mean age of onset, higher percentage of anti-cyclic citrullinated peptide positive people, and lower percentage of affected people carrying shared epitopes in Hispanics than those in Caucasians. A larger sample size of the Hispanic group is needed to identify linkage regions.