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ID PMID Title PublicationDate abstract
19052836 Diagnosis delay in patients with ankylosing spondylitis: factors and outcomes--an Indian p 2009 Mar This study focuses on the causes and consequences of delay in diagnosis of ankylosing spondylitis (AS). Seventy consecutive patients presenting at a rheumatology clinic in India were studied. Mean (+/-S.D) delay in diagnosis was 6.9 (+/-5.2) years. The main cause of delay was incorrect diagnosis as non-specific back pain (19/54, 35.1%), degenerative disc disease (14/54, 25.9%), rheumatoid arthritis (11/54, 20.37%), and tuberculosis of spine (9/54, 16.6%) in that order, for which the patient received prolonged treatment. Absence of extra-articular manifestations and juvenile age also significantly correlated with diagnostic delay. Delay in diagnosis resulted in significantly worse disease activity index (BASDAI), functional index (BASFI), and damage index (BASMI). Most incorrect initial diagnoses were made by orthopedicians (75.9%), followed by general physician (50%), and rheumatologist (12%). Continuing medical education workshops with a focus on clinical diagnosis of inflammatory back pain may help in early diagnosis of AS.
18781847 Pharmacogenetic relevance of MTHFR polymorphisms. 2008 Sep The 5,10-methylenetetrahydrofolate reductase (MTHFR) is a key enzyme for intracellular folate homeostasis and metabolism. Two common MTHFR polymorphisms, C677T and A1298C, which lead to an altered amino acid sequence, have been associated with a decreased enzyme activity and susceptibility to cancer suggesting that these genetic variants may modulate the risk of several malignancies. C667T, and to a lesser extent A1298C polymorphisms, are also reported to influence the cytotoxic effect of fluoropyrimidines and antifolates providing support for their pharmacogenetic role in predicting the efficacy and the toxicity in cancer and rheumatoid arthritis patients. A combined polymorphisms and haplotype analysis may result in a more effective approach than a single polymorphism one. Moreover gene-nutrient/environmental and gene-racial/ethnic interactions have been shown to affect the impact of these MTHFR genetic variants. Further well-designed studies are needed to clarify the role of MTHFR polymorphisms to derive dose adjustment recommendations on the basis of the patient's genotype.
18537616 Progress in the development of matrix metalloproteinase inhibitors. 2008 Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases involved in the degradation and remodeling of extracellular matrix proteins that are associated with the tumorigenic process. MMPs promote tumor invasion and metastasis, regulating host defense mechanisms and normal cell function.Thus, MMP inhibitors (MMPIs) are expected to be useful for the treatment of diseases such as cancer, osteoarthritis, and rheumatoid arthritis. A vast number of MMPIs have been developed in recent years. With the failure of these inhibitors in clinical trials,more efforts have been directed to the design of specific inhibitors with different Zn-binding groups. This review summarizes the current status of MMPIs, the design of small molecular weight MMPIs , a brief description of available three-dimensional MMP structures, a review of the proposed therapeutic utility of MMPIs, and a clinical update of compounds that have entered clinical trials in humans.
18519019 Economic impact of chronic prostatitis. 2007 Jul There are four types of prostatitis, including type I (acute bacterial prostatitis), type II (chronic bacterial prostatitis), type III (chronic prostatitis/chronic pelvic pain syndrome, or CP/CPPS), and type IV (asymptomatic inflammatory prostatitis). These prostatitis conditions account for approximately 2 million office visits each year to primary care physicians and urologists. The annual cost to treat prostatitis is approximately $84 million. Compared with control subjects, men with prostatitis incur significantly greater costs, predominantly due to increased outpatient visits and pharmacy expenses. CP/CPPS is the most common type of prostatitis. The condition is characterized by chronic, idiopathic pelviperineal pain. Due to the lack of effective treatments for CP/CPPS, the per-person costs associated with the condition are substantial and are similar to those reported for peripheral neuropathy, low back pain, fibromyalgia, and rheumatoid arthritis. Costs appear to be higher in men with more severe symptoms. Indirect costs (eg, work and productivity loss) are incurred by many patients with CP/CPPS. Identification of effective treatments for CP/CPPS would be expected to substantially reduce the costs associated with the condition.
19936286 Cardiovascular disease in systemic lupus erythematosus: the role of traditional and lupus 2008 May Atherosclerosis is a chronic inflammatory disorder characterized by immune cell activation, inflammation driven plaque formation and subsequent destabilization. In other disorders of an inflammatory nature, the chronic inflammatory state per se has been linked to acceleration of the atherosclerotic process which is underlined by an increased incidence of cardiovascular disease (CVD) in disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and antiphopholipid (Hughes) syndrome (APS). SLE is an autoimmune disease that may affect any organ. Premature coronary heart disease has emerged as a major cause of morbidity and mortality in SLE. In addition to mortality, cardiovascular morbidity is also markedly increased in these patients, compared with the general population. The increased cardiovascular risk can be explained only partially by an increased prevalence of classical risk factors for cardiovascular disease; it also appears to be related to inflammation. Inflammation is increasingly being considered central to the pathogenesis of atherosclerosis and an important risk factor for vascular disease. Recent epidemiologic and pathogenesis studies have suggested a great deal in common between the pathogenesis of prototypic autoimmune disease such as SLE and that of atherosclerosis.We will review traditional risk factors for CVD in SLE. We will also discuss the role of inflammation in atherosclerosis, as well as possible treatment strategies in these patients.
19626799 [Diffuse interstitial lung disease and connective tissue diseases: study of seven cases in 2008 INTRODUCTION: The diagnosis of diffuse interstitial lung disease non specific in connective tissue disease is difficult because of many differential diagnoses. Lung involvement can affect functional or vital prognosis. We report 7 cases. CASES: We collected data from 60 years old mean patients. Pulmonary localisation was diagnosed after 19 years of evolution of the auto-immune disease. Discovering circumstances were dyspnea and chronic cough. The radiographic and scannographic signs were diffuse because of long diagnosis delay. The underlying auto immune disease was scleroderma, rheumatoid arthritis, Sjögren's syndrome, ankylosing spondylitis, Sharp's syndrome, and multiple autoimmune syndrome. The main treatment was corticosteroids and respiratory physiotherapy. CONCLUSION: Throughout these 7 cases we discuss clinical, radiological and evolutive aspects and we focus on the need of early diagnosis for a better prognosis.
18026025 Researching the management of constipation in long-term care. Part 2. 2007 Oct 25 The management of constipation is a problem in any healthcare setting. Constipation can affect all individuals; older people and those suffering from disabilities and long-term chronic conditions, such as Parkinson's disease and rheumatoid arthritis, are particularly vulnerable. This two-part article is based on a research study carried out in nine care homes, among patients of various ages with a variety of chronic conditions. The aim of the study was to investigate and improve bowel care in long-term care settings. The background to the study, including the definition, causes, risk assessment and management of constipation, were discussed in Part 1 (Castledine et al, 2007). Part 2 presents the main part of the study. Results show that appropriate education of staff improves their knowledge and practice in dealing with constipation. The importance of educating and training all members of the care team, especially healthcare assistants, in the management of bowel care is highlighted. An evidence-based approach using a constipation risk assessment, management of constipation flow chart and an interventions tool are identified as key factors in the ongoing care of patients in long-term settings.
21136762 Clinical proteomics in chronic inflammatory diseases: A review. 2007 Sep There is a need for better markers for the diagnosis and prognosis of chronic inflammatory diseases. Proteomic strategies can be helpful to detect new biomarkers. Proteomic analyses are performed to characterize the behaviour of the system rather than the behaviour of any single component. Since the genome has been unravelled, the proteome received more attention. Aim of this review was to focus on the use of different proteomics techniques to detect potential and/or common biomarkers in chronic inflammatory diseases. The identified and validated proteins detected in the different studies are compared and discussed to conclude if there are some common markers which can be used in the diagnosis and prognosis of the three chronic inflammatory diseases described in this study; multiple sclerosis, rheumatic diseases and lung inflammatory diseases. The heat shock protein family (hsp) was entitled as biomarkers with potential for further research in multiple sclerosis. Myeloid-related protein 8 (MRP-8) was found in three different rheumatoid arthritis (RA) studies with different sample materials and could be a potential marker for RA. α1-Antitrypsin was validated in two studies as a marker for sarcoidosis and α1-antitrypsin was also found to be a marker for cystic fibrosis (CF), together with myeloperoxidase and IgG.
17601661 High expression level of bone degrading proteins as a possible inducer of osteolytic featu 2007 Oct 8 Protein expression of osteopontin (OPN), osteoprotegerin (OPG), bone sialoprotein (BSP), osteocalcin (OC), RANKL and PTHrP was determined by use of immunohistochemical analysis on tissue arrays (48 cases of PVNS, 20 cases of active (a-RA), non-active rheumatoid arthritis (na-RA), and osteoarthritis (OA)). Additionally, gene expression was analysed using complimentary DNA (cDNA) microarrays. All PVNS cases showed a higher level of both protein and gene expression of RANKL, OPN and BSP in comparison with OA cases. Expression of OPG was not significantly different in PVNS compared to OA. The RANKL/OPG expression ratio was significantly higher in PVNS than in OA. High expressions level of proteins involved in bone degradation in PVNS may promote an intra-osseous propagation of the lesion. This evidence suggests that PVNS might respond to treatment using specific inhibitors of RANKL, OPN and BSP.
17582968 The incidence of antinuclear antibodies (ANA) detected by indirect immunofluorescence assa 2007 Human anti-nuclear antibodies (ANA) in Systemic Lupus Erythematosus (SLE) react specificaly with DNA, RNA, several proteins and ribonucleoproteins. Systemic Lupus Erythematosus is the classic type of polysystemic autoimmune disease. The high frequency of ANA is determined in these patients. Actually, all SLE patients are ANA positive. ANA testing by IFA (Indirect Immunofluorescence Assay) is an excellent screening tool for SLE cases, but it is not so highly specific test. Patients with connective tissue diseases, such as rheumatoid arthritis, scleroderma and dermatomyositis are also frequently positive. Results of IFA ANA have relative low specific degree, and for this reason the titration of these specimens to the end point is usually recommended. Indirect immunoflourescence is reference method for ANA testing. Common substrates are thin sections of rodent organs or various types of cell lines. The cell line substrates are preferable to organ sections, because these rapidly dividing cells have higher level for detection of certain clinically relevant antigens such as (e.g., centromere, SSA (Ro) and Scl-70). In this paper we present the results evaluation of ANA incidence, detected by IFA in serum specimens of corresponding clinical patients, during 2005 and 2006.
17554988 [FDG-PET findings of nodular pulmonary amyloidosis with a long-term observation]. 2007 May A 60-year-old woman was referred to our hospital because of an abnormal chest radiograph in May, 2000. She was found to have rheumatoid arthritis in March, 1998, and pharmacologic therapy with anti-rheumatic drug was started. The chest CT scan revealed bilateral multiple lung nodular lesions of various sizes up to 30 mm. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) demonstrated a lesion with intense FDG activity in the right lung with a standardized uptake value (SUV) of 10.1. Fiberoptic bronchoscopy revealed no endobronchial lesions. Video-assisted thoracoscopic surgery was done to ascertain the pathological diagnosis. Histological examination showed that the pulmonary nodules were composed of amyloid A (AA) protein. Secondary Sjögren syndrome was subsequently diagnosed. A diagnosis of localized nodular pulmonary amyloidosis with AA type amyloid protein was made, and therapy with anti-rheumatic drugs was continued. After six years of therapy, the size of pulmonary amyloidoma was reduced, and the accumulation of FDG returned to normal. We reported this interesting case in which FDG-PET apparently reflected the disease activity of pulmonary amyloidosis.
17452815 Immunodeficiency-related Hodgkin lymphoma and its mimics. 2007 May Classic Hodgkin lymphoma (CHL) in patients with underlying immunodeficiency disorders frequently differs from that in the immune competent population in terms of its clinical behavior and pathologic features. Moreover, differential from Hodgkin-like lymphoid proliferations may be problematic. Topics under review include: (a) CHL posttransplant lymphoproliferative disorders, (b) CHL in HIV/AIDS, (c) Hodgkin variant of Richter syndrome in chronic lymphocytic leukemia in association with fludarabine therapy, (d) CHL in other immunodeficiency states including methotrexate-associated lymphoproliferative disorder in patients with rheumatoid arthritis and primary immune deficiencies, and (e) Hodgkin-like lymphoid proliferations including senile Epstein-Barr virus+ B-cell lymphoproliferative disorder. Also under consideration is the pathogenesis of these disorders with an emphasis on the role of Epstein-Barr virus.
17045197 Glucocorticoid action and the development of selective glucocorticoid receptor ligands. 2006 Glucocorticoids are important endocrine regulators of a wide range of physiological systems ranging from respiratory development, immune function to responses to stress. Glucocorticoids in cells activate the cytoplasmic glucocorticoid receptor (GR) that dimerizes, translocates to the nucleus and functions as a ligand-dependent transcriptional regulator. 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, and in some lymphoid cancers, yet its prolonged use has undesirable side effects such as obesity, diabetes, immune suppression and osteoporosis. Detailed knowledge on the mechanism of GR action has led to the development of novel selective glucocorticoid receptor modulators (SGRMs) that show promise of being efficacious for specific treatments of disease but with fewer side effects. SGRMs promote specific recruitment of transcriptional co-regulators that elicit specific gene responses and show promise of greater efficacy and specificity in treatment of inflammatory diseases and type-2 diabetes.
16913666 [Complement activation and inflammation]. 2006 Jul The complement system not only plays an important role in the defense system, but also contributes to the amplification of inflammation if activated in excess or inappropriately controlled. Complement activation through one of three pathways is tightly controlled by various regulators of complement activation (RCA) which are constitutively expressed on various cells in order to restrict excessive activation. Complement activation may generate polypeptides, so-called anaphylatoxins, and membrane attack complex (MAC) with large molecular mass. Anaphylatoxins (C3a, C4a, and C5a) produced by activation of the complement is considered to bridge innate and acquired immunity. Considering that C5a is more potent than C3a, but the serum concentration of C3 is 10 times higher than that of C5, the overall effects of C3a may be comparative with those of C5a. Since both anaphylatoxins are considered to exert their actions through rhodopsin-typed receptors, their receptor antagonists are targets for the discovery of anti-inflammatory and immune-modulating drugs. Complement activation may be related to the pathophysiology of various refractory disorders including ARDS, asthma, septic syndrome, SLE, rheumatoid arthritis, ischemia-reperfusion injury, and psoriasis etc. Pharmacological manipulation of the complement system may consist of various strategies including (1) inhibitors of complement activation at various levels, (2) receptor antagonists of anaphylatoxins, C3a and C5a, and (3) inhibitors of C5a including monoclonal antibody. Candidate agents concerning the above-mentioned manipulations have being produced and some are now in progress toward clinical trials in patients with certain diseases.
16835707 The role of leukotrienes in the pathophysiology of inflammatory disorders: is there a case 2006 Mar Leukotrienes (LTs), a family of lipid mediators, play a key role in the pathogenesis of inflammation. They are synthesized in the leucocytes from arachidonic acid (AA) via the actions of 5-lipoxygenase (5-LO). LTs are classified into two classes: LTB(4) and cysteinyl LTs (CysLTs). LTB(4) is one of the most potent chemoattractant mediators of inflammation. It exerts its actions through a seven transmembrane-spaning G protein receptors, LTB4 R-1 and LTB4 R-2. CysLTs (LTC(4), LTD(4), and LTE(4)) are potent bronchoconstrictors that play an important role in asthma. They induce their actions through G protein coupled receptors, CysLT R-1 and CysLT R-2. LTs are involved in the pathogenesis of inflammatory disorders specially asthma, rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Therefore, LTs modifiers, LTs inhibitors or antagonists, represent important therapeutic advance in the management of inflammatory diseases. Zileuton, zafirlukast and montelukast are LTs modifiers that are approved to use for the treatment of inflammatory disorders.
16451303 Evidence for prescribing exercise as therapy in chronic disease. 2006 Feb Considerable knowledge has accumulated in recent decades concerning the significance of physical activity in the treatment of a number of diseases, including diseases that do not primarily manifest as disorders of the locomotive apparatus. In this review we present the evidence for prescribing exercise therapy in the treatment of metabolic syndrome-related disorders (insulin resistance, type 2 diabetes, dyslipidemia, hypertension, obesity), heart and pulmonary diseases (chronic obstructive pulmonary disease, coronary heart disease, chronic heart failure, intermittent claudication), muscle, bone and joint diseases (osteoarthritis, rheumatoid arthritis, osteoporosis, fibromyalgia, chronic fatigue syndrome) and cancer, depression, asthma and type 1 diabetes. For each disease, we review the effect of exercise therapy on disease pathogenesis, on symptoms specific to the diagnosis, on physical fitness or strength and on quality of life. The possible mechanisms of action are briefly examined and the principles for prescribing exercise therapy are discussed, focusing on the type and amount of exercise and possible contraindications.
16413964 Multiple sclerosis: postlinkage genetics. 2006 Mar Because of the relative failure of linkage analysis in multiple sclerosis, despite the investigation of more than 700 affected relative pairs, we have applied four alternative strategies to identify genes that confer susceptibility to the disease. First, we have reported two clusters of MS patients from isolated populations where 19 and 13 patients, respectively, could be shown to have common ancestry tracing back several centuries. Three and five haplotypes, respectively, were shown to be shared by affected individuals, however, these haplotypes were extended and the statistical evidence modest. Second, we have recently reported the results of a two-stage candidate gene analysis of 66 selected genes, mostly of immune function. The IL-7 receptor alpha gene and LAG-3 both had three SNP markers associated with MS. Third, we recently identified the MHC class II transactivator gene in an animal model with inflammatory properties and later confirmed it to be of importance for MS, rheumatoid arthritis and acute myocardial infarction. Finally, in collaboration with the Serono Genetics Institute, we have completed a genome-wide screen with over 100,000 markers in three sets of 300 MS patients and 300 matched controls. Eighty genes showed evidence of importance in all three populations. These strategies appear to hold some promise of success where linkage analysis has proven less successful than anticipated.
16402217 Biological treatment in rheumatic diseases: results from a longitudinal surveillance: adve 2006 Aug The objective of this study was to assess the long-term safety and tolerability of biologicals in a clinical setting. Data on adverse events (AEs) have been collected over a 5-year period by means of detailed reports sent in to the National Register of Biological Treatment in Finland (ROB-FIN) and validated by information collected by the National Agency for Medicines. Three hundred and eight reports on AEs were filed, concerning a total of 248 patients; this corresponds to 17% of all patients in the ROB-FIN register who started biological treatments. Skin reactions and infections comprised 35 and 28% of the AEs, respectively. Some cases of tuberculosis and other infections, heart failure and demyelinating conditions were seen. Our work demonstrates no unexpected AEs in a Finnish patient cohort consisting of rheumatoid arthritis and spondylarthropathy patients, although many of them were treated with combination treatments in common use in Finland. Biological treatment appears safe in the hands of the Finnish rheumatologists.
19118972 Fatigue communication at the out-patient clinic of Rheumatology. 2009 Jul OBJECTIVE: To describe nurse-patient and rheumatologist-patient interaction in fatigue communication at the rheumatology out-patient clinic. METHODS: Consultations of 20 rheumatoid arthritis (RA) patients with the nurse specialist and the rheumatologist were videotaped and analysed using the Medical Interview Aural Rating Scale (MIARS). Subsequently, patients were asked to fill out a concern questionnaire asking how worried they felt and how satisfied they were with attention given by both healthcare professionals. Finally, patients were interviewed on reasons for being not or not completely satisfied with the care received. RESULTS: Fatigue was discussed in 42% of the rheumatologists' consultations and 83% of the nurse specialists' consultations. RA patients more often used implicit cues instead of explicit concerns related to fatigue. Almost 72% of the patients felt worried about fatigue and in general they were more satisfied with the nurse specialist's attention to fatigue than with the attention from the rheumatologist. CONCLUSION: Fatigue is not structurally communicated at the rheumatology out-patient clinic and exploring and acknowledging communication techniques can help patients to express their concerns about fatigue. PRACTICE IMPLICATIONS: Healthcare professionals must recognise fatigue as a severe problem for RA patients and start the conversation on fatigue instead of waiting for the patient to mention fatigue spontaneously.
19107017 [Effects of smoking on the thyroid gland, digestive system, kidney and bone]. 2008 Dec INTRODUCTION: In addition to being a major cardiovascular risk factor, smoking promotes or worsens thyroid, digestive, renal and bone diseases. BACKGROUND: Smoking is positively associated with hyperthyroidism. It is associated with Graves' disease and it especially increases the risk of the development of severe exophthalmos. In contrast, smoking might exert a protective action for thyroid carcinoma. Smoking increases the severity of hepatic lesions in patients with chronic hepatitis C. Smoking accelerates the progression of primary biliary cirrhosis and increases the risk of hepatocellular carcinoma. Smoking increases risk of both hyperplastic and adenomatous polyps. While Crohn's disease is associated with smoking, ulcerative colitis is largely a disease of non smokers. Smoking increases risk of development of both renal cell carcinoma and chronic nephropathies, particularly in types 1 and 2 diabetes. Smoking is a risk factor for decreased bone density and is associated with a significantly increased risk of fracture. Smoking is related to the development of rheumatoid arthritis and may adversely influence its severity. CONCLUSIONS: Smoking might be considered a risk factor for the development of several thyroid, digestive, renal and bone diseases. Consequently, smoking prevention and cessation programs must be strongly encouraged among the patients concerned.