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ID PMID Title PublicationDate abstract
16865656 Pyoderma gangraenosum, a rare, but potentially fatal complication in paediatric oncology p 2007 Sep Pyoderma gangraenosum (PG) is a serious chronic, ulcerative skin disorder afflicting both adults and children. As PG is often associated with systemic diseases (>50%) such as inflammatory bowel disease, rheumatoid arthritis or haematological disorders, it requires a multidisciplinary approach. This disorder is not commonly reported in paediatrics; therefore children with PG represent a particularly difficult diagnostic challenge. Clinical diagnosis is often delayed and PG is only considered after eliminating other causes of cutaneous ulcers. We report a 4-year-old boy with secondary myelodysplastic syndrome following treatment for acute lymphoblastic leukaemia who presented with a massive inflammatory, ulcerative proliferation of the lower lip which was diagnosed as PG. We have reviewed the literature with reference to diagnostic criteria and treatment options of this disorder that is particularly rare in childhood.
16638026 Endogenous anti-oxidants in pregnancy and preeclampsia. 2006 Apr Oxidative stress has been implicated in a wide variety of diseases and degenerative states including cancer, rheumatoid arthritis, cardiovascular disease and ageing. There is now considerable evidence to suggest that pregnancy leads to the generation of an increased oxidative burden, but whether this overwhelms the anti-oxidant capacity within the placenta and/or the peripheral circulation remains a point of conjecture. There is little doubt that oxidative stress is a significant contributor in the pathogenesis of preeclampsia. The use of exogenous anti-oxidants such as vitamins C and E in the prevention of preeclampsia is the subject of several large clinical trials currently being conducted in many countries around the world. The results of these studies are eagerly awaited, but what of the endogenous anti-oxidant systems that have evolved to combat the oxidative burden associated with living in an aerobic environment? This review will focus on several important anti-oxidant enzyme systems, their role in pregnancy and the evidence to suggest that endogenous anti-oxidants are important in the development of complications of pregnancy such as preeclampsia.
16321545 A review on pro- and anti-angiogenic factors as targets of clinical intervention. 2006 Feb Angiogenesis plays an important role in physiology and pathology. It is a tightly regulated process, influenced by the microenvironment and modulated by a multitude of pro- and anti-angiogenic factors. A thorough understanding of the angiogenic process may lead to novel therapies to target ischemic vascular diseases as well as diseases characterised by excessive angiogenesis such as rheumatoid arthritis, psoriasis or tumours. This review gives an overview of the (groups of) factors involved in different steps of the angiogenic process, divided into factors affecting endothelial proliferation and migration and factors affecting blood coagulation, fibrinolysis and the degradation of basement membranes and the extra-cellular matrix, with a specific emphasis on angiopoietins and their related growth factors. The therapeutic implications of these factors are discussed.
16154142 Regulatory T-cells and autoimmunity. 2006 Jan Approximately 20% of the population is affected by autoimmune or inflammatory diseases mediated by an abnormal immune response. A characteristic feature of autoimmune disease is the selective targeting of a single cell type, organ or tissue by certain populations of autoreactive T-cells. Examples of such diseases include rheumatoid arthritis, insulin-dependent diabetes mellitus, and systemic lupus erythematosus (SLE), all of which are characterized by chronic inflammation, tissue destruction and target organ malfunction. Although strong evidence links most autoimmune diseases to specific genes, considerable controversy prevails regarding the role of regulatory T-cell populations in the disease process. These cells are now also believed to play a key role in mediating transplantation tolerance and inhibiting the induction of tumor immunity. Though the concept of therapeutic immune regulation aimed at treating autoimmune pathology has been validated in many animal models, the development of strategies for the treatment of human autoimmune disorders remains in its infancy. The main obstacles to this include the conflicting findings of different model systems, as well as the contrasting functions of regulatory T-cells and cytokines involved in the development of such disorders. This review examines the role of regulatory T-cells in the pathogenesis of autoimmunity and describes the therapeutic potential of these cells for the prevention of immune-mediated pathologies in the future. Although much remains to be learned about such pathologies, a clearer understanding of the mechanisms by which regulatory T-cells function will undoubtedly lead to exciting new possibilities for immunotherapeutics.
18928162 Neuropsychiatric lupus in patients with lupus glomerulonephritis. 2007 Neuropsychiatric symptoms are recognized to occur in a significant percentage of systemic lupus erythematosus patients and to be a leading cause of morbidity and mortality in lupus. The aim of the present study is to investigate neuropsychiatric symptoms in the patients with lupus nephritis without chronic renal failure. We studied 74 patients (4 male, 70 female) with SLE without chronic renal failure. Disease activity was assessed by the European Consensus Lupus activity Measurement (ECLAM). Renal biopsies disclosed type V lesions in 23 patients, type IV--in 34, type III--in 3, type II--in 11, type I--in 3 patients. Two control groups are used--with rheumatoid arthritis (96 patients) and 63 healthy subjects. The most frequent clinical manifestations are cognitive dysfunction (52.94%), headache (29.41%), psychoses (17.65%), epileptic seizures (20.59%) etc., and the most common cognitive deficit is related to impairment of the memory. The tests for cognitive disorders and nuclear magnetic resonance are the methods of investigation, by which the nervous system injuries are most early detected in the course of the disease. The presented study describes the correlations between the immunologic deviations (antiribosomal P-antibodies, aPL, aSm, aC1q), MMP-9, AT III and the NP injuries.
20476960 Use of rituximab in multiple sclerosis: current progress and future perspectives. 2008 Sep In recent years, new insights into the immunological pathways in multiple sclerosis (MS) have been detected. This increasing knowledge has led to more distinct treatment options in modifying the disease course of MS. In 2006, natalizumab, an alpha4-integrin monoclonal antibody, introduced a new era of MS treatment. Another promising drug is the monoclonal CD20-antibody rituximab, which depletes CD20(+) cells, pre-B cells and mature B cells. Rituximab is approved for the treatment of a number of autoimmune diseases other than MS, such as rheumatoid arthritis and non-Hodgkin's lymphoma. Early-phase trials in the autoimmune-driven disorders Sjögren's syndrome, vasculitis and thrombocytopenic purpura confirmed the use of rituximab in B-cell-mediated diseases. Another autoimmune disease affecting the CNS is neuromyelitis optica (NMO). NMO is characterized by having some similarities with MS and several studies demonstrated successful therapy of NMO using rituximab. In addition, numerous case reports in MS patients showed a stabilization of the course with a reduction of the relapse rate and MRI pathologies in MS patients. To date, one Phase II clinical trial in MS patients confirmed the results from these case reports. In this article, we will focus on the role of B cells in MS and the immunomodulatory pathways of rituximab. Recent data from experimental and clinical trials, as well as safety aspects, are discussed. A future perspective is given regarding the possible role of rituximab, as well as possible other candidates for treating MS.
16574269 Antisense strategies in degenerative joint diseases: sense or nonsense? 2006 May 20 Oligodeoxynucleotides, ribozymes, and RNA interference make part of the antisense strategy, a new tool proposed to conquer cancer, viral infections, as well as cardiovascular and rheumatic diseases. The silencing effect of antisense strategies is both highly specific and potent - and only requires that the sequence of the target RNA is known. However, so far neither RNAi nor ribozymes have been approved for clinical use and only a single antisense agent is on the market. In the context of degenerative joint diseases, experimental data in the field of antisense strategies are still rare. Several studies from rheumatoid arthritis (RA), an inflammatory condition that leads to the progressive destruction of cartilage and bone within affected joints, however revealed promising results and taught us important lessons that might also be useful in therapeutic approaches for osteoarthritis (OA). To introduce these therapies in clinical practice, however, several hurdles still have to be overcome.
16404564 Rheumatic diseases and chronic myelogenous leukemia, presentation of four cases and review 2006 Jul We report four patients with rheumatic disease (RD) and chronic myelogenous leukemia (CML). In two patients with Behcet's disease (BD) and rheumatoid arthritis (RA), CML developed after RD, in two patients with diffuse cutaneous systemic sclerosis and spondyloarthropathy, RD was diagnosed after CML. A variety of interactions have been described between hematological malignancies and RD. Nevertheless, few cases of RD have been documented associated with CML. It is unclear whether the development of CML in patients with RD and RD development after CML occurs by chance alone, is due to the underlying disease, or is facilitated by drugs. Whatever the cause is, it should be kept in mind that CML may develop in the course of RD and RD may be seen in CML patients.
18765313 Familial multiple myeloma associated with disorders of chronic inflammation: first report 2008 Aug Multiple myeloma (MM) is a malignancy arising from mature plasma cells in the bone marrow and usually presents with bone destruction, hypercalcemia, anemia, renal damage, and increased susceptibility to infection. The etiology of MM is unknown, with no established lifestyle, occupational, or environmental risk factors. Because MM is an uncommon disease, etiologic assessments can be difficult. It has been reported to be in association with sarcoidosis, and in a few cases, rheumatoid arthritis. Familial type of MM with an autosomal dominant heredity pattern has also been reported. The genetic loci affected in these cases are still unknown. Herein we present a family with 3 affected cases in an autosomal dominant inheritance pattern. The first case was a man diagnosed to have immunoglobulin (Ig)A-type myeloma at the age of 50. The history revealed 2 more cases in the family: an uncle diagnosed to have unsecretory-type myeloma at the age of 76 and a cousin (the daughter of the affected uncle) who was diagnosed at the age of 48 years to have IgG-type myeloma and did not respond to therapy. This patient also had a history of sarcoidosis preceding the diagnosis of myeloma. All other affected family members had been treated for dental-oral infection (including chronic gingivitis) for 3 and 4 years before the diagnosis of myeloma. Karyotype analysis revealed pseudohypodiploidy and deletion of chromosome 13q in only the patient with coexisting sarcoidosis. To our knowledge, this is the first report on familial myeloma from Turkey. This family enhances the role of hereditary factors and chronic inflammation in the etiology of MM.
18680473 Influence of polymorphic N-acetyltransferases on non-malignant spontaneous disorders and o 2008 Jul Polymorphic N-acetyl transferases (NAT) 1 and 2 are involved in detoxification of xenobiotic arylamines and hydralazines. These common environmental chemicals may be related to the pathogenesis of many spontaneous disorders, mainly malignancies, but also disimmune or degenerative diseases, for which a polygenic predisposition has been suggested. Hence, polymorphic NAT genes (NAT2 has been the most studied one) may be low-penetrance risk genes for some of these disorders. Although a relation of risk may be definitely discarded for systemic lupus erythematosus (SLE), inflammatory bowel disease and endometriosis, more research is needed for rheumatoid arthritis, Parkinson's, Alzheimer's, Behçet's and periodontal diseases , as current results are inconclusive but suggest a possible relation with NAT2 polymorphism. In diabetes mellitus the possible relation with the rapid phenotype may be due to acquired metabolic changes and more genotyping studies are needed. NAT2 slow metabolizers are more prone to the side effects of polymorphically acetylated drugs, as is the SLE-like syndrome induced by hydralazine and procainamide, the side effects due to sulphasalazine and the skin rash secondary to many sulphonamides. Future research should be based on well-designed studies, with adequate sample sizes and homogeneous recruitment criteria, to obviate the proliferation of small studies that are time- and resource-consuming without offering definite answers.
18564830 [Restless legs syndrome]. 2008 Mar The restless legs syndrome (RLS) is a common neurological disorder to take possession of increasing attention. RLS is characterized by an urge to move the legs, usually accompanied by uncomfortable or unpleasant sensations, that occurs or worsen at rest and is relieved by activity. The symptoms of RLS have a major impact on nocturnal sleep and daytime functions. The clinical diagnostic criteria were established and published in 2003 by International Restless Legs Syndrome Study Group (IRLSSG). All four essential criteria must be met for a positive diagnosis. However, RLS encompassed an idiopathic form of genetic or unknown origin and secondary forms associated with many causes. Special awareness should be kept for differential diagnosis such as uremia, iron deficiency anemia, polyneuropathy, rheumatoid arthritis, and other neurodegenerative diseases. Polysomnography, actinography, L-dopa loading test, and suggested immobilization test (SIT) are helpful tools to reduce the diagnostic puzzle of false positive and false negative. Pathophysiological concepts of RLS are essentially based on the neuroimaging and neurophysiological data to assume a dysfunction of the dopaminergic system, possibly on the All neuron group localized in the hypothalamus. These neurons modulate spinal excitability and alter the sensory processing predominantly of leg afferents. Treatment may be closely linked to the dopaminergic system and iron metabolism. Dopaminergic stimulation with levodopa or dopamine agonists is the first choice in idiopathic restless legs syndrome, but the long-term adverse effect of augmentation should be carefully monitored.
18558334 Production of recombinant tumor necrosis factor receptor/Fc fusion protein by genetically 2008 May We previously reported the production of recombinant proteins using genetically manipulated chickens and quails. In this study, we constructed a retroviral vector encoding an expression cassette for a fusion protein of the extracellular domain of the human tumor necrosis factor (TNF) receptor 2 and Fc region of human IgG1 (TNFR/Fc), which is expected as an effective drug for inflammatory diseases such as rheumatoid arthritis. The concentrated viral vector was injected into developing chicken embryos. The chickens that hatched stably produced TNFR/Fc in the serum and egg yolk for six months. It appears that the fused protein is transported and accumulated into yolk from the serum, which is mediated by the Fc receptor. The protein purified from the yolk and serum inhibited the cytotoxic activity of TNF-* toward L929 cells, indicating that the protein produced by the chickens is biologically active. These results indicate the effectiveness of the recovery of Fc-fused proteins from the yolk of genetically manipulated chickens.
18537597 Beyond hemostasis: the role of platelets in inflammation, malignancy and infection. 2008 Jun Platelets play a complex role in hemostasis and thrombosis. The expression of multiple membrane receptors, both constitutive and activation-dependent, mediates platelet adhesion and aggregation at sites of vascular lesion. Platelet activation leads to exocytosis of granular constituents, release of newly synthesized mediators, and discharge of membrane-bound transcellular signaling molecules. Many of the same mechanisms that play a role in hemostasis and thrombosis facilitate platelet participation in other physiological or pathological processes including inflammation, malignancy and the immune response. Platelet receptors such as GPIb/IX/V, P-selectin, P-selectin glycoprotein ligand 1, CD40 and the alphaIIbbeta3 integrin, crucial to hemostasis, have been implicated in the progression of such inflammatory conditions as atherosclerosis, rheumatoid arthritis and inflammatory bowel disease, in the progression and metastatic spread of malignancies, and in the immune response to bacterial challenge. The release of platelet granular contents, including adhesive proteins, growth factors and chemokines/cytokines, that serve to facilitate hemostasis and wound repair, also function in acute and chronic inflammatory disease and in tumor cell activation and growth. Platelets contribute to host defence as they recognise bacteria, recruit traditional immune cells to the site of infection and secrete bactericidal mediators. The primary focus of this review is the "non-haemostatic" functions of platelets in physiological and pathological states.
18466562 Modeling activation of inflammatory response system: a molecular-genetic neural network an 2007 Significant alterations of T-cell function, along with activation of the inflammatory response system, appear to be linked not only to treatment-resistant schizophrenia, but also to functional psychoses and mood disorders. Because there is a relatively high comorbidity between rheumatoid arthritis (RA), schizophrenia and major depression, the question arises whether there is a common, genetically modulated inflammatory process involved in these disorders. On the basis of three family studies from the U.S. and Europe which were ascertained through an index case suffering from RA (599 nuclear families, 1868 subjects), we aimed to predict the inter-individual variation of autoantibody IgM levels, as an unspecific indicator of inflammatory processes, through molecular-genetic factors. In a three-stage strategy, we first used nonparametric linkage (NPL) analysis to construct an initial configuration of genomic loci showing a sufficiently high NPL score in all three populations. This initial configuration was then modified by iteratively adding or removing genomic loci such that genotype-phenotype correlations were improved. Finally, neural network analysis (NNA) was applied to derive classifiers that predicted the phenotype from the multidimensional genotype. Our analysis led to an activation model that predicted individual IgM levels from the subjects' multidimensional genotypes very reliably. This allowed us to use the activation model for an analysis of the DNA of an existing sample of 1003 psychiatric patients in order to test, in a first approach, whether a deviant, genetically modulated inflammatory process is involved in the pathogenesis of major psychiatric disorders.
18372435 C-reactive protein, anti-C-reactive protein antibodies and clinical atherosclerosis. 2008 Feb There has been considerable interest in the relationship between C-reactive protein (CRP) and atherosclerosis. We have previously demonstrated that individuals, especially those with rheumatoid arthritis and systemic lupus erythematosus, may produce antibodies to CRP. This study was therefore undertaken to determine the possible association between anti-CRP antibodies and atherosclerosis. A total of 103 individuals were identified with or without atherosclerosis, and without clinical rheumatic diseases. They were evaluated with respect to cholesterol, HDL, LDL, high-sensitivity (hs)CRP, and anti-CRP antibody levels, as well as use of statin medications. Individuals with atherosclerosis were much more likely to be taking a statin, and thus have lower lipid levels. However, there was no association between hsCRP or anti-CRP antibody levels with atherosclerosis, statin use, or each other. These observations suggest that anti-CRP antibody is not involved in atherosclerosis, and may represent an epiphenomenon.
18343043 Could calcitonin be a useful therapeutic agent for trigeminal neuralgia? 2008 Trigeminal neuralgia (TN) has been recognized as one of the most common neurovascular syndromes caused by the vascular contact of the trigeminal nerve in its root entry zone (REZ) with a branch of the superior or anterior inferior cerebellar arteries, leading to a demyelinization of trigeminal sensory fibers within either the nerve root or, less commonly, the brainstem. There is a lack of certainty regarding the aetiology and pathophysiology of TN, therefore the treatment of trigeminal neuropathic pain disorders continues to be a major therapeutic challenge. The identification of novel therapeutic agents for the treatment of these disorders is important. Calcitonin (especially intranasal) provides an interesting analgesic effect in a series of painful conditions including reflex sympathetic dystrophy syndrome, adhesive capsulitis, ankylosing spondylitis, rheumatoid arthritis, vertebral crush fractures and metastasis, phantom limb pain, etc. Exogenous calcitonin is thought to cross the blood-brain barrier and to accumulate slowly in the brain, inducing analgesia once sufficient receptors are occupied. We hypothesize that calcitonin may has anti - trigeminal neuralgia properties. From the clinical point of use, the analgesic effect of calcitonin will be beneficial throughout the whole period of medical treatment of trigeminal neuralgia patients.
18220873 Haematopoietic stem cell gene therapy to treat autoimmune disease. 2006 Sep Autoimmune diseases affect approximately 6% of the population and are characterised by a pathogenic immune response that targets self-antigens. Well known diseases of this nature include type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis. Treatment is often restricted to replacement therapy or immunosuppressive regimes and to date there are no cures. The strategy of utilising autologous or allogeneic haematopoietic stem cell transplantation to treat autoimmunity and induce immunological tolerance has been trailed with various levels of success. A major issue is disease relapse as the autoimmune response is reinitiated. Cells of the immune system originate from bone marrow and have a central role in the induction of immunological tolerance. The ability to isolate and genetically manipulate bone marrow haematopoietic stem cells therefore makes these cells a suitable vehicle for driving ectopic expression of defined autoantigens and induction of immunological tolerance.
18041408 Regeneration of the skeleton by recombinant human bone morphogenetic proteins. 2007 Sep Recombinant human bone morphogenetic proteins (rhBMPs) have past a long journey in human orthopaedic surgery during the last 15 years. From the first reports of the use of rhBMPs in hostile environments such as critically-sized bone defects, avascular femoral head necrosis, unstable thoracolumbar vertebral fractures, instability between the atlas and axis due to rheumatoid arthritis; over the use for nonunions of long bones and the scaphoid, reconstructive and revision surgeries of the hip, acute fractures, allograft nonunions, congenital pseudarthrosis, and various approaches of lumbar and cervical spine fusions, rhBMPs overgrow to a safe and reliable device in the treatment of open tibial shaft fractures, nonunions of long bone fractures, anterior lumbar interbody fusion and revision posterolateral lumbar fusions. Systematic review of the published literature of rhBMPs is presented.
17954295 D-Penicillamine-induced ANCA-associated crescentic glomerulonephritis in Wilson disease. 2007 Nov Several drugs, including hydralazine and propylthiouracil, can induce antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. d-Penicillamine was implicated in a few patients with rheumatoid arthritis or systemic sclerosis, but in patients with both diseases, ANCA-associated vasculitides were described in the absence of the drug. Therefore, the role of d-penicillamine treatment could not be established. We report the first case of antimyeloperoxidase antibody-associated vasculitis in a patient treated with d-penicillamine for Wilson disease. Because Wilson disease was never associated with ANCA-related nephritis, this case strongly supports that d-penicillamine can induce ANCA-vasculitis. The presentation and rapidly progressive and potentially severe outcome of this complication dramatically contrast with those of membranous and minimal change glomerulopathy, also induced by the sulfhydryl compound.
17711409 A polymorphic variant in the MHC2TA gene is not associated with systemic lupus erythematos 2007 Nov Single-nucleotide polymorphisms (SNPs) in the major histocompatibility complex class II transactivator (MHC2TA) gene encoding the class II transactivator have been associated with multiple sclerosis, rheumatoid arthritis, and myocardial infarction in the Swedish population. We used a case-control approach to investigate the prevalence of a relevant variant in Swedish systemic lupus erythematosus (SLE) cohorts to determine whether SLE shares the same MHC2TA susceptibility allele as the other diseases. No differences were observed between cases and control subjects at either the allele or genotype levels. Furthermore, no significant correlations were found when comparing different clinical and serological SLE phenotypes. This particular polymorphism rs3087456 of the MHC2TA gene does not appear to influence genetic susceptibility to SLE in the Swedish population. We conclude that our data support neither allelic nor genotype association between the MHC2TA SNP and SLE.