Rheumatoid Arthritis: Australia

Hoi AY, Iskander MN, Morand EF. · Centre for Inflammatory Diseases, Monash Institute of Medical Research, Monash University, Melbourne, Australia. · Inflamm Allergy Drug Targets. · Pubmed #17897055 No free full text.

Abstract: Macrophage migration inhibitory factor (MIF), a cytokine originally reported in the 1960s as the prototypic T lymphokine, has emerged in recent years as a key factor regulating inflammatory responses. Both by directly activating immune cells, and by participating in activation entrained by other stimuli, MIF is important in innate and adaptive immune responses as well as tissue-specific mechanisms of damage. As a consequence of its involvement in multiple stages of the immune-inflammatory response, MIF has the potential to be involved in the pathogenesis of a range of immune-mediated inflammatory diseases affecting multiple organ systems. Diseases in which a role for MIF has been strongly validated include rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, atherosclerosis, asthma, inflammatory liver disease, and most recently systemic lupus erythematosus. Recent data have provided mechanisms of action for MIF which further support its suitability as a therapeutic target. Finally, MIF has a unique relationship with glucocorticoids, acting to counter-regulate their anti-inflammatory effects, such that MIF antagonist therapy may be a direct route to 'steroid-sparing'. Methods of targeting MIF therapeutically have also emerged in recent years, based on the unique protein structure of MIF which affords opportunities for direct antagonism by small molecules, as well as by protein therapeutics such as monoclonal antibodies. Clinical trials of MIF antagonist therapies are likely before the end of the current decade.

Lutzky V, Hannawi S, Thomas R. · Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia. · Arthritis Res Ther. · Pubmed #17850683 links to  free full text

Abstract: Dendritic cells are the major antigen-presenting and antigen-priming cells of the immune system. We review the antigen-presenting and proinflammatory roles played by dendritic cells in the initiation of rheumatoid arthritis (RA) and atherosclerosis, which complicates RA. Various signals that promote the activation of NF-kappaB and the secretion of TNF and IL-1 drive the maturation of dendritic cells to prime self-specific responses, and drive the perpetuation of synovial inflammation. These signals may include genetic factors, infection, cigarette smoking, immunostimulatory DNA and oxidized low-density lipoprotein, with major involvement of autoantibodies. We propose that the pathogenesis of RA and atherosclerosis is intimately linked, with the vascular disease of RA driven by similar and simultaneous triggers to NF-kappaB.

Mackay F, Groom JR, Tangye SG. · The Autoimmunity Research Unit, The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia. · Curr Opin Rheumatol. · Pubmed #17762603 No free full text.

Abstract: PURPOSE OF REVIEW: This review provides an update on the specific, strong association between dysregulated production of the cytokine B-cell activation factor and Sjögren's syndrome, and offers new perspectives on potential pathogenic mechanisms. RECENT FINDINGS: Excess B-cell activation factor in mice triggers Sjögren's syndrome-like symptoms, and elevated serum B-cell activation factor in humans correlates with Sjögren's syndrome. B-cell activation factor is produced locally by activated monocytes, T cells and dendritic cells, and by epithelial cells and infiltrating B cells. Moreover, recent data in humans suggest that the innate immune system plays a role as an initiator of immune disorders in inflamed tissues. SUMMARY: Recent data have demonstrated the critical role of B-cell activation factor and B cells in the pathogenesis of Sjögren's syndrome, and its association with B lymphomas. Moreover, B-cell depleting treatments have confirmed the critical role of B cells in Sjögren's syndrome. Excess B-cell activation factor possibly corrupts B-cell tolerance and allows the emergence of self-reactive B cells that efficiently present antigen to T cells. In addition, B-cell activation factor may stimulate T-cell independent activation of B cells via Toll-like receptors; this recently identified mechanism could also play a separate, detrimental role in autoimmunity.

Hazy MD, Slavotinek J, Smith MD. · Division of Medical Imaging, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia. · Australas Radiol. · Pubmed #17533688 No free full text.

Abstract: This report reviews imaging methods used for diagnosis and monitoring of rheumatoid arthritis, with emphasis on the role of ultrasonography. Traditionally, conventional radiography has been useful in detecting and monitoring the extent of joint destruction in rheumatic disease. However, it is particularly difficult to detect pathological joint changes in the early stages. Magnetic resonance imaging is able to detect inflammation of the synovial membrane and erosions but is limited by cost and availability. Ultrasound has recently emerged as a useful and potentially reliable method for assessing the degree of joint inflammation and erosion in patients with early rheumatoid arthritis.

Clark IA. · School of Biochemistry and Molecular Biology, Australian National University, Canberra, ACT, Australia. · Cytokine Growth Factor Rev. · Pubmed #17493863 No free full text.

Abstract: This review summarizes the origins of the insight that excess production of pro-inflammatory cytokines caused a constellation of changes that contribute to pathophysiology of disease. This connection was made following the original 1975 TNF (tumor necrosis factor) publication from New York describing how activated macrophages kill tumors. The study caught the eye of a group in London who were trying to understand how the same in vivo macrophage activation would protect mice against the erythrocytic protozoan parasites that cause malaria and babesiosis. Based on collaborative research between these two groups, it was argued in 1981 that TNF and related cytokines initiated events that caused pathology, as well as parasite death within red cells in these infectious diseases. This proved to be a key conceptual advance. It was also argued that the pathology of bacterial sepsis logically had TNF origins. Once TNF was cloned in 1985, allowing its specific analysis in serum and neutralization in vivo, the involvement of this cytokine in infectious disease pathology was pursued by a number of groups. Some researchers found that once "their" cytokine was cloned and sequenced, they had been unwittingly expanding knowledge on TNF for several years. By the late 1980s excess TNF production was proposed to be central to acute systemic viral diseases. This family of cytokines is now at the centre of investigations to understand the mechanisms of acute systemic viral diseases, including influenza and the hemorrhagic viral diseases. With its implication as the master regulator of other inflammatory cytokines in the synovial membrane, TNF has also become the major cytokine in the pathogenesis of chronic inflammatory disease. Its neutralization has proven to be a potent treatment for rheumatoid arthritis and Crohn's disease.

Mackay F, Silveira PA, Brink R. · The Autoimmunity Research Unit, The Garvan Institute of Medical Research, Darlinghurst, NSW, Australia. · Curr Opin Immunol. · Pubmed #17433868 No free full text.

Abstract: B-cell activation factor from the tumor necrosis factor family (BAFF) is a key survival factor during B-cell maturation -- a delicate immune checkpoint for B cells. Excessive BAFF production at this stage corrupts B-cell tolerance and leads to autoimmunity. Elevated serum BAFF levels have been detected in some patients suffering from various autoimmune conditions. The positive outcomes of currently ongoing clinical trials using BAFF-neutralising agents confirm that this factor plays a major pathological role in rheumatoid arthritis and in systemic lupus erythematosus. Almost a decade after its discovery, BAFF continues to occupy the main stage in Immunology, with more than one hundred BAFF-related articles published per year. In recent years, our understanding of cell signaling and autoimmune mechanisms in this system have seen major advances, refining new possibilities for therapeutic intervention.

Morand EF. · Centre for Inflammatory Disease, Monash University Department of Medicine/Monash Institute for Medical Research, Monash Medical Centre, Clayton, Melbourne, Victoria, Australia. · Curr Opin Rheumatol. · Pubmed #17414960 No free full text.

Abstract: PURPOSE OF REVIEW: Glucocorticoids are used in the treatment of most rheumatic diseases, and are used chronically in up to 50% of cases of rheumatoid arthritis. The frequency of their use has in the past been incompletely supported by trial evidence of their benefit and by incomplete understanding of their mechanisms of action. The present review will examine significant recent publications relating to glucocorticoids of relevance to rheumatology RECENT FINDINGS: The basic science of glucocorticoid action has advanced considerably in the review period. Major advances include demonstration of the function of glucocorticoid-induced anti-inflammatory proteins such as mitogen-activated protein kinase phosphatase-1, expanded understanding of alternately spliced isoforms of the glucocorticoid receptor, and major steps in understanding factors regulating glucocorticoid sensitivity in disease. Clinical studies have also had major developments, most strikingly with the publication of two randomized prospective studies on the efficacy of glucocorticoids in preventing erosions in rheumatoid arthritis. SUMMARY: Despite over 50 years of glucocorticoid use in rheumatology, basic science and clinical studies continue to yield intriguing new data. The quest for therapeutic agents with the beneficial effects of glucocorticoids but lacking their harmful effects is aided by this progress.

Joshua F, Lassere M, Bruyn GA, Szkudlarek M, Naredo E, Schmidt WA, Balint P, Filippucci E, Backhaus M, Iagnocco A, Scheel AK, Kane D, Grassi W, Conaghan PG, Wakefield RJ, D'Agostino MA. · Department of Rheumatology, St. George Hospital, University of NSW, Sydney, Australia. · J Rheumatol. · Pubmed #17407235 No free full text.

Abstract: This report presents the results of a recent systematic review performed by the OMERACT Ultrasound Group on the metric properties of ultrasound for the detection of synovitis in inflammatory arthritis. Reviews were conducted for the hand, wrist, elbow, shoulder, knee, ankle, and foot; most reports were related to the hand and knee, and the most common disease process was rheumatoid arthritis. The review highlights the current gaps in the literature, including a lack of reliability data with respect to intra-occasion and intra- and inter-reader reliability. Current work by our group is addressing these issues.

Gillespie MT. · St Vincent's Institute of Medical Research, Princes Street, Fitzroy 3065, Victoria, Australia. · Arthritis Res Ther. · Pubmed #17381830 links to  free full text

Abstract: Historically, the osteoblast has been considered the master cell in the control of osteoclast development and, therefore, bone resorption. Now the interactions between cells of the immune system and bone cells have redefined our thinking on the regulation of bone resorption. Moreover, the crosstalk between these cell types has special significance in inflammatory conditions such as rheumatoid arthritis. This report highlights the contribution that T lymphocytes make in regulating osteoclast formation and bone resorption.

Grulich AE, Vajdic CM, Cozen W. · National Centre in HIV Epidemiology and Clinical Research, Level 2, 376 Victoria Street, Darlinghurst, NSW 2010, Australia. · Cancer Epidemiol Biomarkers Prev. · Pubmed #17337643 links to  free full text

Abstract: This review examines the association between disorders of immunity, including immune deficiency, atopy, and autoimmune disease, and non-Hodgkin lymphoma (NHL). Immune deficiency is one of the strongest known risk factors for NHL. Risk is increased whether the immune deficiency is congenital, iatrogenic, or acquired. Risk of NHL increases with degree of immune deficiency, and there is no evidence of a threshold. In the profoundly immune deficient, NHL is frequently caused by infection with the ubiquitous EBV. Whether mild, subclinical immune deficiency is related to increased NHL risk is unknown. There is inconsistent evidence that atopic conditions, such as asthma, hayfever, and eczema, characterized by an immune response that is skewed toward Th2, are associated with a decreased risk of NHL. These data come mainly from case-control studies. Concern has been expressed that the association may be due to reverse causality if early symptoms of NHL include a lessening of atopic manifestations. Case-control and cohort studies of people with autoimmune conditions have generally shown that rheumatoid arthritis, systemic lupus erythematosis, and Sjogren's disease are associated with increased NHL risk. It seems to be the intensity of the inflammatory disease rather than its treatment which is related to increased risk of NHL. The study of altered immunity as a cause of NHL in case-control studies is limited by the fact that development of NHL in itself leads to altered immunity. Cohort studies of the role of altered immunity should be a top priority in epidemiologic studies of NHL etiology.

Gronthos S, Zannettino AC. · Mesenchymal Stem Cell Group, Division of Haematology, Institute of Medical and Veterinary Science, Hanson Institute, Adelaide, South Australia, Australia. · Trends Endocrinol Metab. · Pubmed #17320408 No free full text.

Abstract: The chemokine CXCL12 (variously termed stromal-derived factor 1 or B cell-stimulating factor) is a highly conserved chemotactic cytokine belonging to the large family of CXC chemokines. CXCL12 has crucial roles in the formation of multiple organ systems during embryogenesis and in the regulation of bone marrow haematopoiesis and immune function in the postnatal organism. Although considered an important factor in normal bone metabolism, recent studies implicate CXCL12 in the pathogenesis of several diseases involving the skeleton, including rheumatoid arthritis and cancers that metastasize to bone. Recent studies have highlighted an emerging role for CXCL12 in the processes of physiological and pathological bone remodelling.

Romas E, Gillespie MT. · The University of Melbourne, St. Vincent's Hospital, 41 Victoria Parade, Fitzroy, 3065, Australia. · Rheum Dis Clin North Am. · Pubmed #17288976 No free full text.

Abstract: Inflammatory synovitis induces profound bone loss and OCLs are the instrument of this destruction. TNF blockers have an established role in the prevention of inflammatory bone loss in RA; however, not all patients respond to anti-TNF therapy and side effects may prevent long-term treatment in others. The B-cell--depleting antibody rituximab and the T-cell costimulation blocker abatacept are emerging as major treatment options for patients who are resistant to anti-TNF [96,97]. Proof-of-concept studies demonstrate that targeting RANK-mediated osteoclastogenesis prevents inflammatory bone loss and clinical application has only just begun. The efficacy of RANKL inhibition has been witnessed in trials of Denosumab, and RANKL-neutralizing antibodies are likely to become the treatment of choice for blocking RANKL in RA [77,78]. A major limitation of RANKL antagonism is that it does not treat synovitis. Therefore, anti-RANKL therapy most likely will be used in the context of MTX therapy. There is uncertainty about the possible extraskeletal adverse effects of long-term effects of long-term RANKL blockade. In particular, anti-RANKL therapy could jeopardize dendritic cell function or survival. The demonstrable role of OCLs in inflammation-induced bone loss also invites a reconsideration of the new BPs for bone protection [98]. Studies of ZA in preclinical models indicate that bone protection is comparable to that afforded by OPG. One possible caveat is that intravenous BPs are linked to jaw osteonecrosis [99], although the incidence is confined mainly to intensive treatment in the oncology setting. Although pulsed PTH stimulated bone formation in arthritic models, it has yet to be proven clinically in the context of powerful OCL inhibition with TNF or RANKL antagonists. With strategies that normalize OCL numbers, clinicians are poised to accomplish effective prevention of inflammation-induced bone loss.

Le NT, Xue M, Castelnoble LA, Jackson CJ. · Sutton Arthritis Research Laboratories, Institute for Bone and Joint Research, University of Sydney, Level 1, Building 35, Royal North Shore Hospital, St Leonards, New South Wales, 2065, Australia. · Front Biosci. · Pubmed #17127395 No free full text.

Abstract: Collagen, gelatin, elastin, fibronectin, proteoglycans and vitronectin are just a few proteins which form the "mesh" that holds a multicellular organism together. The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that degrade the extracellular matrix. Over several decades it has been clearly established that MMPs are the key molecules associated with matrix remodeling. The remodeling of this matrix is important for physiological and pathological processes such as pregnancy, wound repair, cancer and arthritis. The identification of new non-matrix MMP substrates involved in inflammation, highlights the diverse role of MMPs. These enzymes can enhance leukocyte invasion and regulate the inflammatory activity of serine proteases, cytokines and chemokines. Interestingly, the MMP family appears to have a "dual personality" in that several MMPs such as MMP-2 and -9 can favour either anti- or pro-inflammatory action, respectively. The extent of this dual functionality of MMPs is yet to be realized. Elucidating these processes may assist in the development of drugs for the treatment of inflammatory diseases such as arthritis, cancer and chronic wounds.

Walker JG, Littlejohn GO. · Centre for Mental Health Research, Australian National University, Canberra 0200, Australia. · Clin Rheumatol. · Pubmed #17124551 links to  free full text

Abstract: Musculoskeletal disorders often have associated pain, functional impairment and work disability, and, not surprisingly, are the most common reasons for utilizing healthcare resources. Rheumatoid arthritis (RA) and fibromyalgia (FM) are causes of musculoskeletal pain and disability. Research indicates that there is a widespread impact of RA and FM on physical, psychological and social factors in affected individuals, and thus, outcome measures that encompass multiple aspects of quality of life are needed. Generic measures of quality of life identify associations between physical conditions and mental health and highlight the need to address psychological functioning to ultimately improve the individuals' quality of life.

Neill J, Belan I, Ried K. · School of Nursing and Midwifery, Flinders University, Adelaide, Australia. · J Adv Nurs. · Pubmed #17118041 No free full text.

Abstract: AIM: This paper reports a systematic review of non-pharmacological interventions for fatigue in adults with three common autoimmune conditions. BACKGROUND: A considerable proportion of people with multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus experience compromised quality of life due to fatigue. Recent reviews of pharmacotherapies for fatigue in these conditions remain inconclusive, and systematic evidence for effectiveness of non-pharmacological interventions was unavailable. Our paper addresses this gap. METHODS: The literature search used the key words fatigue, energy, multiple sclerosis, rheumatoid arthritis and systemic lupus. It included 19 electronic databases and libraries, three evidence-based journals, two internet search engines, was dated 1987-2006, and limited to English. Non-pharmacological experimental studies about fatigue comprising more than five adults were included. Meta-analysis was not possible due to diverse interventions and outcome measures, therefore studies were analysed by types of interventions used to reduce fatigue. RESULTS: Of 653 hits, 162 papers were reviewed, and 36 met the inclusion criteria. Thirty-three primary studies reported 14 randomized controlled trials and 19 quasi-experimental designs. Most interventions were tested with people with multiple sclerosis. Exercise, behavioural, nutritional and physiological interventions were associated with statistically significant reductions in fatigue. Aerobic exercise was effective, appropriate and feasible for reducing fatigue among adults with chronic autoimmune conditions. Electromagnetic field devices showed promise. The diversity of interventions, designs, and using 24 different instruments to measure fatigue, limited comparisons. CONCLUSION: Low impact aerobic exercise gradually increasing in intensity, duration and frequency may be an effective strategy in reducing fatigue in some adults with chronic auto-immune conditions. However, fatigue is a variable and personal experience and a range of behavioural interventions may be required. Well-designed studies testing these promising strategies and consensus on outcome fatigue measures are needed.

Haynes DR. · Department of Pathology, University of Adelaide, Adelaide, South Australia, 5005, Australia. · Inflammopharmacology. · Pubmed #17093901 No free full text.

Abstract: Currently there are many emerging therapies for the treatment of chronic osteoporosis. This is a major problem world wide and particularly of concern in post-menopausal women. This has offered a large expanding market for the pharmaceutical industry and consequently large amounts of money and resources have been used to develop new treatments. These new and emerging treatments have largely targeted the mechanisms of bone loss associated with post-menopausal osteoporosis. However, there are many other important bone loss disorders and it is possible that some of these new therapies may be useful in treating bone loss associated with other diseases. This review identifies several of these pharmacologic treatments of osteoporosis and discusses the possibility of using these drugs for the treatment of bone loss associated with inflammatory diseases. In addition, other approaches, such as regulating apoptosis and intracellular signalling, may be developed in the future and may better target bone loss associated with chronic inflammation are identified.

Khalil AA, Hall JC, Aziz FA, Price P. · School of Surgery and Pathology, The University of Western Australia, Perth, Western Australia, Australia. · ANZ J Surg. · Pubmed #17054552 No free full text.

Abstract: Tumour necrosis factor alpha (TNF-alpha) is an inflammatory cytokine primarily produced by macrophages. It is a unique protein with contradictive properties; it has the ability to induce cellular death by apoptosis and oncosis, but can also induce cellular regeneration and growth. Genetic polymorphisms in TNFA have been associated with poor outcome in some surgical patients and this may provide a useful tool to screen for high-risk patients. Manipulating TNF-alpha levels in vivo may influence the progression of several pathological conditions. TNF-alpha has anti-cancer properties and has been used to treat cancer patients. Treatment with anti-TNF-alpha drugs and antibodies has been successful in rheumatoid arthritis and other autoimmune diseases, but disappointing in the management of patients with sepsis. This review article focuses on the biological activities, genetic polymorphism of TNFA and the role of TNF-alpha and anti-TNF-alpha treatments, based on animal experiments and clinical trials.

Cole TJ. · Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia. · Biotechnol Annu Rev. · Pubmed #17045197 No free full text.

Abstract: 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.

Joshua F, Edmonds J, Lassere M. · Rheumatology Department, St. George Hospital, Kogarah, NSW, Australia. · Semin Arthritis Rheum. · Pubmed #17023258 No free full text.

Abstract: OBJECTIVE: To evaluate the performance characteristics of power Doppler ultrasound as a diagnostic and monitoring tool in the assessment of musculoskeletal disease through a systematic review of the literature. METHODS: Search Strategy: We performed a literature search of PUBMED (1966 to June 2005). Selection Criteria: Only original research reports written in English involving musculoskeletal disease and power Doppler ultrasound were included. Reviews were noted but not included. Data Extraction/Reporting: The design, subjects, methods, imaging protocols, and performance characteristics studied in the research papers were reported. RESULTS: Of 3568 identified reports, 139 involved power Doppler ultrasound of the musculoskeletal system. Fifty-three of these reports met the inclusion criteria. Ultrasound machine settings were specified in 63% of reports. Rheumatoid arthritis was the most commonly studied musculoskeletal disease (64% of papers). Validity was the most studied performance characteristic (94% of reports), while reliability and responsiveness were studied in 17 and 34%, respectively. CONCLUSIONS: Although the majority of research reports of power Doppler ultrasound assessment of the musculoskeletal system evaluated validity, less than half reported reliability and responsiveness. Further work is needed to evaluate power Doppler ultrasound assessment of the musculoskeletal system before it can be used to guide clinical decisions or be used as an endpoint in clinical trials.

Eyles JL, Roberts AW, Metcalf D, Wicks IP. · Reid Rheumatology Laboratory, Division of Autoimmunity and Transplantation, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. · Nat Clin Pract Rheumatol. · Pubmed #16951705 No free full text.

Abstract: Recent studies have highlighted the functional capacity of neutrophils as powerful mediators of tissue inflammation. Granule-packaged proteases and reactive oxygen intermediates, which are important for intracellular digestion during phagocytosis, are released from neutrophils during inflammation. In the extracellular environment, neutrophil-derived proteases can cause local tissue damage, but also regulate the activity of cytokines, cytokine receptors and chemokines. Neutrophils can themselves produce an array of inflammatory mediators, including cytokines, chemokines and complement; these cells also express Fc receptors, which can bind and possibly transport immune complexes into the extravascular compartment, as well as activating neutrophils at opsonised surfaces. Blood-borne neutrophils interact with, and then exit through, the endothelium of blood vessels, after which these cells die and must be removed safely. The balance between neutrophil survival and clearance is crucial to the resolution of inflammation. A major regulator of neutrophil production and survival is the cytokine granulocyte colony-stimulating factor (G-CSF). Treatment with G-CSF can exacerbate underlying inflammatory diseases in humans and mice, and G-CSF deficiency is profoundly protective against collagen-induced arthritis in mice. These findings implicate G-CSF as an important proinflammatory cytokine. This article discusses the roles of neutrophils and G-CSF during chronic inflammatory diseases.

Chin D, Boyle GM, Theile DR, Parsons PG, Coman WB. · Melanoma Genomics Group, The Queensland Institute of Medical Research, Herston, Brisbane 4029, Queensland, Australia. · J Plast Reconstr Aesthet Surg. · Pubmed #16920579 No free full text.

Abstract: The mapping and sequencing of the human genome has generated a large resource for answering questions about human disease. This achievement is akin in scientific importance to developing the periodic table of elements. Plastic surgery has always been at the frontier medical research. This resource will help us to improve our understanding on the many unknown physiological and pathogical conditions we deal with daily, such as wound healing keloid scar formation, Dupuytren's disease, rheumatoid arthritis, vascular malformation and carcinogenesis. We are primed in obtaining both disease and normal tissues to use this resource and applying it to clinical use. This review is about the human genome, the basis of gene expression profiling and how it will affect our clinical and research practices in the future and for those embarking on the use of this new technology as a research tool, we provide a brief insight on its limitations and pitfalls.

Sutherland AP, Mackay F, Mackay CR. · The Immunology and Inflammation Research Program, The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia. · Pharmacol Ther. · Pubmed #16863659 No free full text.

Abstract: In an effort to develop more effective treatments for inflammatory diseases, immunologists have targeted numerous molecular pathways, but with limited success. Notable exceptions are anti-TNF agents, which have proved efficacious in a proportion of rheumatoid arthritis (RA) patients. Another TNF family member, termed BAFF ("B cell-activating factor belonging to the TNF family"), plays a central role in autoimmune diseases, as well as in B cell maturation, survival, and T cell activation. Agents that block BAFF have proven to be highly effective in the treatment of certain autoimmune conditions in mice. In addition, phase II data in human clinical trials for RA appear very promising. BAFF is also a survival factor for certain B cell lymphomas. Despite the relatively recent identification of BAFF, this molecule has provided considerable new insight into B cell homeostasis and immune function, and represents an important new molecular target for treatment of autoimmune diseases and lymphomas.

Lassere MN. · Department of Rheumatology, St George Hospital, Gray Street, Kogarah, NSW 2217, Australia. · Osteoarthritis Cartilage. · Pubmed #16785055 No free full text.

Abstract: Measurement is fundamental to science. In medicine measurement underpins most clinical decisions. Outcome measures for rheumatoid arthritis clinical trials (OMERACT) is an informal collaborative group of professionals dedicated to improving outcome measurement in the rheumatic disease. The methodologic hallmark of the OMERACT process is captured in the OMERACT filter--truth, discrimination, and feasibility. Using the key elements of the OMERACT filter a comprehensive checklist for evaluating reported measures is provided. The checklist guides the potential user through a series of questions. The checklist is also an important resource for researchers working in the field of measurement.

Aeberli D, Leech M, Morand EF. · Centre for Inflammatory Diseases, Monash Medical Centre, Locked Bag No 29, Clayton Melbourne 3168, Australia. · Rheumatology (Oxford). · Pubmed #16705047 links to  free full text

Abstract: Glucocorticoids (GCs) are widely used in the treatment of inflammatory diseases including rheumatoid arthritis (RA). Treatment with GC is associated with significant dose-dependent side-effects. The pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) has emerged in recent years as a candidate factor which could regulate GC sensitivity. MIF is induced by GC, and is able to override anti-inflammatory actions of GCs. In this review, we summarize the pro-inflammatory actions of MIF with respect to RA, describe the interactions between MIF and GC and examine new evidence, which identifies MIF as a specific target for steroid sparing.

Perkins AV. · Heart Foundation Research Centre, School of Medical Science, Griffith University Gold Coast Campus, Southport, Queensland, Australia. · Aust N Z J Obstet Gynaecol. · Pubmed #16638026 No free full text.

Abstract: 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.