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ID PMID Title PublicationDate abstract
18046677 Catastrophic antiphospholipid syndrome: report of 4 cases. 2007 Nov Catastrophic antiphospholipid syndrome (CAPS), described by Asherson in 1992, is a rare form of antiphospholipid syndrome resulting in multiorgan failure with a mortality rate of about 50%. The syndrome occurs in patients with either systemic lupus erythematosus and other rheumatic diseases (systemic sclerosis, rheumatoid arthritis, primary Sjogren syndrome) or alone. Whereas in "classic" antiphospholipid syndrome (APS), medium-large vessels are involved, a diffuse small vessel ischemia and thrombosis (microangiopathic disease) leading to a severe multiorgan dysfunction is predominant in CAPS. "Trigger" factors have been demonstrated in 45% of patients, but in the majority, they remain unknown. Not infrequently, CAPS arises in patients without any previous thrombotic history. The kidney is the organ most commonly affected, followed by the lung, the central nervous system, the heart and the skin. Disseminated intravascular coagulation occurs in approximately 13% of patients. The present study reports the clinical and serological features of 4 patients affected by this rare form of antiphospholipid syndrome. Nephrologists should be aware of the possibility of this syndrome as a cause of multiorgan failure since prompt recognition is essential for effective treatment.
17979026 Treatment options for refractory Wegener's granulomatosis: a role for rituximab? 2007 Nov Wegener's granulomatosis (WG) is a small-vessel vasculitis of unknown etiology, involving mainly the upper airways, lungs and kidneys. Organ inflammatory damage is mediated by anti-neutrophil cytoplasm antibodies, and their detection is a component of the diagnostic work-up as well as clinical signs and symptoms, and histopathological biopsy abnormalities. Conventional therapeutic regimens, such as cyclophosphamide and corticosteroids, can be used to induce and maintain disease remission. Alternatively, other cytotoxic agents (eg, methotrexate or mycophenolate mofetil), anti-TNFalpha agents (eg, infliximab or etanercept) or anti-lymphocyte antibodies (eg, rituximab) can be used. Rituximab, a mAb which targets CD20+ B-cells, is currently used in the treatment non-Hodgkin's lymphoma and rheumatoid arthritis, and is being investigated for refractory WG therapy and other autoimmune diseases.
17907437 Pigmented villonodular synovitis in children: a report of six cases and review of the lite 2007 We report six children with pigmented villonodular synovitis. They ranged in age from seven to fifteen years. In four patients, the knee was involved. One patient had involvement of the ankle, and one had diffuse involvement along a metacarpal. In five cases, the diagnosis was not suspected clinically or radiographically, and the delay in making the correct diagnosis was as long as two years. Clinical diagnosis in these five patients was usually bacterial synovitis or juvenile rheumatoid arthritis. We feel that the diagnoses of pigmented villonodular synovitis should be considered in any child with chronic joint effusion.
17847104 NA1/NA2 heterozygote of Fcgr3b is a risk factor for progression of IgA nephropathy in Chin 2007 Several studies have identified FcgRIIIb (Fcgr3b) polymorphisms that determine susceptibility to autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. The objective of the study was to clarify whether Fcgr3b allele polymorphism influence susceptibility to immunoglobulin A nephropathy (IgAN), clinical features or severity in patients with IgAN. Deoxyribonucleic acid (DNA) fragments were amplified by polymerase chain reaction (PCR) using genomic DNA from 172 unrelated, healthy blood donors and 128 IgAN patients in our Kidney Disease Centre. The present findings showed that Fcgr3b genotype influenced the disease susceptibility and severity of IgAN, although Fcgr3b polymorphism did not affect the age of the disease onset. We found that the genotype frequency of Fcgr3b heterozygote NA1/NA2 in IgAN patients in Chinese significantly higher than that of healthy donors. Furthermore, higher genotype frequency of NA1/NA2 was found also in IgAN patients with glomerulosclerosis or crescent formation than those without it. NA1/NA2 heterozygote of Fcgr3b is a risk factor for progression of IgA nephropathy in Chinese.
17765316 Potential of p38-MAPK inhibitors in the treatment of ischaemic heart disease. 2007 Nov Chronic heart failure is debilitating, often fatal, expensive to treat and common. In most patients it is a late consequence of myocardial infarction (MI). The intracellular signals following infarction that lead to diminished contractility, apoptosis, fibrosis and ultimately heart failure are not fully understood but probably involve p38-mitogen activated protein kinases (p38), a family of serine/threonine kinases which, when activated, cause cardiomyocyte contractile dysfunction and death. Pharmacological inhibitors of p38 suppress inflammation and are undergoing clinical trials in rheumatoid arthritis, Chrohn's disease, psoriasis and surgery-induced tissue injury. In this review, we discuss the mechanisms, circumstances and consequences of p38 activation in the heart. The purpose is to evaluate p38 inhibition as a potential therapy for ischaemic heart disease.
17359217 HUMIRA pen: a novel autoinjection device for subcutaneous injection of the fully human mon 2007 Mar The HUMIRA (adalimumab) Pen is a novel, integrated, disposable autoinjection delivery system for the subcutaneous injection of adalimumab. Adalimumab is a biological disease modifier for the treatment of rheumatoid arthritis and other chronic debilitating diseases mediated by tumor necrosis factor. Sustaining long-term efficacy with a biological therapy is influenced by patient adherence to the therapeutic regimen, which is often affected by the route of drug administration. Self-administered injectables offer several advantages over intravenous injections (i.e., portability, convenience and flexible scheduling). In particular, patients with chronic, debilitating diseases may need a self-administered medication available in an easy-to-use and convenient delivery device that minimizes pain and facilitates adherence to therapy. The adalimumab Pen offers these benefits and recent evidence indicates that patients overwhelmingly prefer the adalimumab Pen to the prefilled syringe.
16951216 Vascular endothelial growth factor signaling pathways: therapeutic perspective. 2006 Sep 1 The establishment of a vascular supply is one of the earliest and most important events occurring during embryonic development. Growth and maturation of a functional vascular network are complex and still incompletely understood processes involving orchestrated activation of vascular progenitors in the early stages of embryonic development followed by vasculogenesis and angiogenesis. These processes require a tightly regulated activation of several growth factors and their receptors. The role of vascular endothelial growth factors (VEGF) and their receptors has been studied extensively due to their prominent role during blood vessel formation. Mice deficient in various VEGF ligands or receptors show serious defects in vascular formation and maturation. Moreover, members of the VEGF family are involved in other significant biological processes, including lymphangiogenesis, vascular permeability, and hematopoiesis. Importantly, VEGF is released by tumor cells and induces tumor neovascularization. It is now well established that the VEGF axis represents an important target for antitumor therapy. Aberrant VEGF signaling is also a feature of several other pathologic conditions, such as age-related macular degeneration and rheumatoid arthritis.
16920576 Cyclosporine A for the treatment of autoimmune disorders in HCV infected patients. 2006 Aug Due to the relatively high prevalence of both HCV infection and autoimmune disorders (AD), it is not rare to encounter patients with AD also carrying HCV. Considering that the use in HCV infected individuals of corticosteroids or immunosuppressant drugs, that are indeed needed to treat AD, is considered a risk for worsening the clinical outcome of HCV infection, rheumatologist have often refrained from using these drugs in AD when HCV-RNA is also present. Cyclosporine (CsA) is an immunosuppressive agent used to treat a wide range of autoimmune disorders but there is in literature a large body of evidence suggesting that CsA also exerts an inhibitory effect on HCV replication at standard therapeutic dose. The anti-HCV effect of CsA has been demonstrated both in vitro and in vivo. Therefore, these evidences have opened new ways to improve the therapy and the prognosis in patients with HCV-related liver diseases including transplanted ones. Recent reports, although limited in number, also suggest the safety of CsA, in the treatment of patients with AD and concomitant HCV infection. Good results have also been obtained in the treatment in rheumatoid arthritis patients even in association with anti-TNF agents.
16633945 The role of statins in clinical medicine--LDL--cholesterol lowering and beyond. 2006 Jan 21 In the past years, statins have emerged as the most important class of lipid lowering agents. Through inhibition of HMG-CoA reductase, they restrict the rate-limiting step of cholesterol synthesis, which leads to upregulation of LDL receptors on the cell membrane and thus reduction of atherogenic LDLs. This effect translates into clinical benefit by reducing cardiovascular events both in primary and secondary prevention settings. As an approximate rule, statin therapy leads to a relative risk reduction of 25-30% in most of the large randomised controlled trials. Stroke risk is reduced to a similar degree. Despite initial concerns, the currently available statins have a favourable safety profile; however, potential interactions with other drugs must be considered. Recently, characteristics unrelated to LDL lowering have been intensively studied. These pleiotropic statin effects result from decreased levels of isoprenoid intermediates of cholesterol synthesis. They include--among others--anti-inflammatory, anti-proliferative, and immunomodulatory actions. Pleiotropic effects favourably influence pathomechanisms of plaque formation. Furthermore, they may prove beneficial in the prevention or treatment of diseases unrelated to atherosclerosis, eg rheumatoid arthritis, multiple sclerosis, or cancer.
16455071 Free immunoglobulin light chains as target in the treatment of chronic inflammatory diseas 2006 Mar 8 Immunoglobulin free light chains were long considered irrelevant bystander products of immunoglobulin synthesis by B lymphocytes. To date, different studies suggest that free light chains may have important functional activities. For instance, it has been shown that immunoglobulin free light chains can elicit mast cell-driven hypersensitivity responses leading to asthma and contact sensitivity. Free light chains also show other biologic actions such as anti-angiogenic and proteolytic activities or can be used as specific targeting vehicles. Levels of free light chain levels in body fluids increase markedly in diseases such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. In this review, we will focus on the unexpected biological activities of immunoglobulin free light chains with special attention to its possible role in the induction of chronic inflammatory diseases.
18852828 LASSO-Patternsearch algorithm with application to ophthalmology and genomic data. 2008 The LASSO-Patternsearch algorithm is proposed to efficiently identify patterns of multiple dichotomous risk factors for outcomes of interest in demographic and genomic studies. The patterns considered are those that arise naturally from the log linear expansion of the multivariate Bernoulli density. The method is designed for the case where there is a possibly very large number of candidate patterns but it is believed that only a relatively small number are important. A LASSO is used to greatly reduce the number of candidate patterns, using a novel computational algorithm that can handle an extremely large number of unknowns simultaneously. The patterns surviving the LASSO are further pruned in the framework of (parametric) generalized linear models. A novel tuning procedure based on the GACV for Bernoulli outcomes, modified to act as a model selector, is used at both steps. We applied the method to myopia data from the population-based Beaver Dam Eye Study, exposing physiologically interesting interacting risk factors. We then applied the the method to data from a generative model of Rheumatoid Arthritis based on Problem 3 from the Genetic Analysis Workshop 15, successfully demonstrating its potential to efficiently recover higher order patterns from attribute vectors of length typical of genomic studies.
16724798 B cell tolerance--how to make it and how to break it. 2006 A series of checkpoints for antigen receptor fitness and specificity during B cell development ensures the elimination or anergy of primary, high-avidity-autoantigen-reactive B cells. Defects in genes encoding molecules with which this purging of the original B cell repertoires is achieved may break this B cell tolerance, allowing the development of B cell- and autoantibody-mediated immune diseases. Furthermore, whenever tolerance of helper T cells to a part of an autoantigen is broken, a T cell-dependent germinal center-type response of the remaining low--or no--autoreactive B cells is activated. It induces longevity of these B cells, and expression of AiD, which effects Ig class switching and IgV-region hypermutation. The development of V-region-mutant B cells and the selections of high-avidity-autoantigen-reactive antibodies producing B cells by autoantigens from them, again, can lead to the development and propagation of autoimmune diseases such as lupus erythematosus or chronic inflammatory rheumatoid arthritis by the autoantibody BcR-expressing B cells and their secreted autoantibodies.
16376013 CNS demyelination in autoimmune diseases. 2006 Mar Autoimmune diseases represent a diverse group of disorders that have generally of unknown etiology and poorly understood pathogenesis. They may be organ-specific or systemic, giving rise to overlapping syndromes; more than one autoimmune disease may occur in the same patient. Numerous case reports have documented that multiple sclerosis (MS) may be present concurrently with other autoimmune diseases, most commonly rheumatoid arthritis, autoimmune thyroid disease, type I diabetes mellitus and pernicious anemia. Case reports of disseminated encephalomyelitis (DEM) coincidental with other autoimmune diseases are rare. Many of systemic autoimmune diseases cause central nervous system (CNS) demyelination and are frequently then diagnosed as MS, whereas they often are instances of DEM, the result of vascular, granulomatous or postinfectious manifestations. We have reviewed 15 patients with autoimmune diseases and CNS demyelination in order to determine the nature of the demyelinating process.
18384191 A systematic review on the Rosa canina effect and efficacy profiles. 2008 Jun Rose hip, rose hip and seed and rose hip seed, all were negatively monographed by the German Commission E due to insufficient evidence of effects and effectiveness. Therefore a comprehensive review of the literature was conducted to summarize the pharmacological and clinical effects of Rosa canina L. to reevaluate its usefulness in traditional medicine. For various preparations of rose hip and rose hip and seed, antioxidative and antiinflammatory effects have been demonstrated. Lipophilic constituents are involved in those mechanisms of action. The proprietary rose hip and seed powder Litozin has been employed successfully in a number of exploratory studies in patients suffering from osteoarthritis, rheumatoid arthritis and low back pain. However, the sizes of the clinical effects for the different indications need to be determined to assure clinical significance. There is also a rationale behind the use of Litozin as part of a hypocaloric diet based on the rose hip probiotic, stool regulating and smooth muscle-relaxing actions, as well as the rose hip seed lipid-lowering, antiobese and antiulcerogenic effects. Further research is needed to clarify the importance of the reported promising experimental effects in clinical use and to characterize the optimum rose hip seed oil preparation for topical use in the treatment of skin diseases.
18310919 Quantitation of biotin-binding immunoglobulins G, A, and M in Human Sera Using F(ab')2anti 2008 Mar Biotin-binding IgG (B-IgG) in human sera was quantified using previously developed F(ab')(2)anti-human IgG-coated multiwell microplates (Muratsugu M. et al., 2003, Biol. Pharm. Bull., 26, 1605--1608). The levels of B-IgG in sera, however, were higher than those we predicted. In this study, we modified the assay using F(ab')2anti-human IgG-coated multiwell microplates and successfully quantified the levels of B-IgG in sera. The cause of the unpredicted results was discussed in the text. In addition, the levels of biotin-binding IgA (B-IgA) and IgM (B-IgM) in sera could be measured using F(ab')2anti-human IgA- or IgM-coated multiwell microplates. We quantified B-IgG, B-IgA, and B-IgM in sera from healthy specimens and patients with bronchial asthma, atopic dermatitis, epilepsy, and juvenile rheumatoid arthritis.
17967730 A clinical approach to autoantibody testing in systemic autoimmune rheumatic disorders. 2007 Nov Musculoskeletal (MSK) disorders constitute one of the most common clinical presentations to clinical care givers. Within this category of illnesses, systemic autoimmune rheumatic diseases (SARD) such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren's syndrome (SjS) and rheumatoid arthritis (RA) are included in the differential diagnosis. A hallmark of SARD is the production of autoantibodies, which are routinely requested as a guide to diagnosis and clinical decision making. The field of serological tests, including the detection of autoantibodies, is complex and often leads to confusion and misunderstanding. When used appropriately, autoantibodies can be a valuable adjunct to the diagnosis, and occasionally therapy and prognosis, of SARD. The role of autoantibody testing and a 'practical' approach to using these tests is the focus of this paper.
17551370 The Wnt signaling pathway and bone metabolism. 2007 Jul PURPOSE OF REVIEW: The Wnt signaling pathway has been a major focus of effort in the bone field for the past 5 years. This review will examine some of the seminal findings that have brought us to our current understanding of the role of this pathway in bone metabolism. RECENT FINDINGS: The Wnt/beta-catenin signaling pathway has been shown to play a major role in bone cell differentiation, proliferation and apoptosis. It is a critical component of bone mass regulation and required for bone to respond to mechanical loading. The pathway is tightly regulated by a number of modulator proteins. Mutations in pathway components that result in aberrant regulation are involved in a number of bone diseases. SUMMARY: Understanding the role that the Wnt signaling pathways play in the regulation of bone metabolism offers great promise for the developmental of new paradigms and pharmaceutical strategies for the treatment of various diseases such as osteoporosis, rheumatoid arthritis and osteoarthritis. Progress in this regard has already been made.
17477483 Considerations and preliminary proposals for defining a reference case for economic evalua 2007 May Since healthcare resources are scarce, choices have to be made on how they will be allocated. The use of economic evaluations using cost-effectiveness analyses has increased rapidly as policymakers have realized their value in maximizing the population's benefits (in terms of length of life and health status) within a given budget. Following efforts by OMERACT to create reference case definitions for the conduct of economic evaluation in rheumatoid arthritis, osteoporosis, and osteoarthritis, we review various methodological areas and research decisions that could benefit from a consensus between researchers, clinicians, and drug developers in terms of an ankylosing spondylitis (AS) reference case. Ten methodological issues are presented that will be important for future development of evaluations. Tentative proposals to define the issues in a reference case for AS are made, along with recommendations for further research.
17410291 Extrahepatic manifestations of chronic HCV infection. 2007 Mar Several extrahepatic manifestations have been reported in the natural history of hepatitis C virus infection (HCV). Up to 40-74% of patients infected with HCV might develop at least one extrahepatic manifestation during the course of their disease. Mixed Cryoglobulinemia (MC) is the most known and studied syndrome associated with HCV infection. It is a systemic vasculitis that may involve the skin, kidney and nervous system. A frequent reported association is that between HCV infection and non-Hodgkin lymphoma. The cryoglobulinemia may be the intermediary disorder, in fact some persistent forms of cyoglobulinemia can switch over to a more aggressive haematologic disorder. As compared to cutaneous vasculitis described in MC, HCV infection has been associated with dermatological disorders such as porphyria cutanea tarda and lichen planus. Thyroid disease (usually hypothyroidism) is commonly seen in people with HCV. Up to 25% have thyroid antibodies. Several studies described a correlation between HCV and lympho-cytic sialoadenitis, similar to sialoadenitis associated with idiopathic Sjögren syndrome, but we can define as "pseudo- Sjögren syndrome" the one associated with HCV infection, because it shows several differences in the idiopathic form. In the course of chronic HCV infection, a common obser-vation are rheumatological symptoms such as polyarthritis. The clinical pattern of joint involvement in the course of HCV infection varies from a rheumatoid arthritis-like form (very rare), to a non erosive oligoarthritis involving the large-sized and middle joints.
16288807 Microcytosis in agnogenic myeloid metaplasia: prevalence and clinical correlates. 2006 Jun Microcytosis is a characteristic laboratory feature for both iron deficiency anemia and thalassemia. It is also infrequently seen in "anemia of chronic disease" that accompanies a spectrum of chronic conditions including rheumatoid arthritis, polymyalgia rheumatica, diabetes mellitus, connective tissue disease, and protracted infection. In addition, there is a well established but pathogenetically obscure association of microcytosis with Hodgkin's lymphoma, Castleman's disease, and renal cell carcinoma. In the current study, we show that microcytosis is a frequent laboratory feature in agnogenic myeloid metaplasia and investigate its clinical relevance in the particular setting.