Eculizumab therapy and complement regulation in a case of resistant catastrophic antiphospholipid syndrome.

Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening form of antiphospholipid syndrome characterised by diffuse arterial and venous thrombosis, in the presence of positive antiphospholipid antibodies. The multiple sites of thrombosis in small, medium and large vessels progress to multiorgan failure, accounting for the high mortality rate associated with CAPS. Unregulated complement activation is increasingly recognised as critical to the pathogenesis of CAPS.

Abdominal vagus nerve stimulation alleviates collagen-induced arthritis in rats.

Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory disease. Despite therapeutic advances, a significant proportion of RA patients are resistant to pharmacological treatment. Stimulation of the cervical vagus nerve is a promising alternative bioelectric neuromodulation therapeutic approach.

Paraneoplastic systemic lupus erythematosus associated with colorectal cancer.

A 64-year-old gentleman initially presented with nephrotic syndrome and membranous nephropathy with positive staining for C1q, which was suspicious for lupus membranous nephritis. Investigation led to the simultaneous diagnosis of colorectal cancer (CRC). The CRC was surgically excised and the patient's nephrotic syndrome resolved.

Perceptions of Doppler ultrasound for rheumatoid arthritis disease activity assessment and education.

Aim: The aim of this qualitative study was to report the findings of the Defining rheumatoid arthritis progression using Doppler Ultrasound in Clinical practice (DEDUCE) Medical Practice Activity, which was developed to facilitate the utilization of Doppler ultrasound (DUS) by Australian rheumatologists in the treatment of patients with rheumatoid arthritis (RA).

Method: Twenty-one rheumatologists recruited a total of 80 patients with RA in Disease Activity Score of 28 joints (DAS28) remission for DUS assessment and completed a pre- and post-activity questionnaire assessing their experience with DUS, as well as a 6-month follow-up questionnaire. Rheumatologists discussed DUS results with patients using visual aids.

Is RANKL inhibition both anti-resorptive and anabolic in rheumatoid arthritis?

A small peptide, OP3-4, blocks receptor activator of NF-κB from binding to its ligand, receptor activator of NF-κB ligand (RANKL), and was reported recently to inhibit bone resorption, promote bone formation and protect cartilage in a preclinical rheumatoid arthritis model. The latter effects may result from inhibition of RANKL reverse signalling in osteoblasts and chondrocytes. Whether other RANKL inhibitors, such as denosumab, share this action is not known, but OP3-4 at least has potential to provide anabolic treatment for both systemic and focal bone loss in inflammatory arthritis.

Parthenolide inhibits pro-inflammatory cytokine production and exhibits protective effects on progression of collagen-induced arthritis in a rat model.

Objectives: Progressive destruction of synovial joint cartilage and bone occurs in pathological conditions such as rheumatoid arthritis (RA) because of the overproduction of pro-inflammatory cytokines and activation of nuclear factor kappa B (NF-κB). Through the screening of NF-κB inhibitors by a luciferase reporter gene assay, we identified parthenolide (PAR) as the most potent NF-κB inhibitor, among several PAR analogue compounds. This study was undertaken to determine whether PAR inhibits pro-inflammatory cytokine production, cartilage degradation, and inflammatory arthritis.

A prospective study of acute inpatient gout diagnoses and management in a tertiary hospital: the determinants and outcome of a rheumatology consultation.

Background: Despite acute gout frequently complicating hospital admissions, diagnosis and management are variable. Rheumatology input may improve patient outcomes.

Aim: To examine acute episodes of inpatient gout in a tertiary hospital to determine (i) factors that may lead to rheumatology input being sought and (ii) the differences in outcomes when rheumatology input occurs.

Oncostatin M acting via OSMR, augments the actions of IL-1 and TNF in synovial fibroblasts.

Objective: To identify how the gp130-signaling cytokine oncostatin M (OSM), acting alone or in concert with IL-1β or TNFα, affects synovial fibroblast expression of genes relevant to inflammation and bone erosion in inflammatory arthritis.

Methods: Synovial fibroblasts (SFs) were isolated from non-arthritic wild type (WT) or OSM receptor deficient (OSMR(-/-)) mice and stimulated with OSM, IL-1β or TNFα and their combinations. Cytokine gene expression was assessed by quantitative RT-PCR.

Australian and New Zealand national evidence-based recommendations for the investigation and follow-up of undifferentiated peripheral inflammatory arthritis: an integration of systematic literature research and rheumatological expert opinion.

Aim: To develop Australian and New Zealand (ANZ) recommendations for the investigation and follow-up of undifferentiated peripheral inflammatory arthritis (UPIA) using an evidence-based approach.

Methods: Ten questions pertaining to the investigation and follow-up of patients with UPIA in daily rheumatological practice were defined by clinicians using a modified Delphi approach. A systematic literature search was conducted for each of the final questions.

Alternative use of bisphosphonate therapy for rheumatic disease.

Bisphosphonates are widely use for pathologies such as osteoporosis, Paget's disease or bone metastasis. However, their potent antiresorptive properties open new therapeutic opportunities for other conditions associated with an increased focal or systemic bone remodelling. Moreover, apart from their antiresorptive activity, bisphosphonates could also have others properties through a specific analgesic or anti-inflammatory effect.

Thioflavin T fluorescence in human serum: correlations with vascular health and cardiovascular risk factors.

Objectives: Amyloid fibrils and amyloid-like structures are implicated in atherosclerosis via macrophage activation and inflammation. A common property of amyloid-like structures is their ability to induce thioflavin T (ThT) fluorescence. We measured ThT fluorescence in serum and related these levels to traditional cardiovascular risk factors and non-invasive measures of vascular dysfunction (elasticity).

Clinical applications of RANK-ligand inhibition.

An enhanced rate of bone remodelling fuelled by osteoclastogenesis mediates diseases such as osteoporosis, arthritic bone destruction, Paget's disease and malignancy-induced bone loss. Thus, the control of osteoclastogenesis is of major clinical importance. The receptor activator of nuclear factor kappa B (RANK); its ligand, RANKL and decoy receptor, osteoprotegerin, are critical determinants of osteoclastogenesis, and increased RANK signalling is involved in several bone diseases, providing the rationale for RANKL inhibition.

The 'iron salute' in haemochromatosis.

The presentation of haemochromatosis is typified by abdominal pain, arthralgia and fatigue or weakness. Arthropathy may be the major presenting feature. The detection of an osteoarthritis-like process involving the metacarpophalangeal (MCP) and wrist joints in middle aged men should signal the possibility of under lying haemochromatosis.

Inflammation-induced bone loss: can it be prevented?

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].

Traditional risk factor assessment does not capture the extent of cardiovascular risk in systemic lupus erythematosus.

Background: Systemic lupus erythematosus (SLE) is associated with accelerated atherosclerosis. However, the degree of endothelial dysfunction and its relationship to traditional and novel cardiovascular risk factors have not been examined in SLE.

Methods: In a case-control design, 35 patients with clinically stable SLE and 35 control subjects matched for age, sex, body mass index and smoking status were studied.

Bone loss in inflammatory arthritis: mechanisms and therapeutic approaches with bisphosphonates.

The inflammatory process in rheumatoid arthritis provokes intense bone resorption, evidenced as bone erosions, juxta-articular osteopenia and generalized osteoporosis. These types of bone loss share a common pathogenesis, and the role of osteoclasts in focal bone erosion was verified in elegant animal studies. The tumour necrosis factor (TNF) family of cytokines and receptors--specifically TNF-alpha, RANKL, RANK and OPG--are dominant regulators of osteoclastic bone resorption in rheumatoid arthritis.

Targeting osteoclasts with zoledronic acid prevents bone destruction in collagen-induced arthritis.

Objective: To study the effect of zoledronic acid (ZA) on synovial inflammation, structural joint damage, and bone metabolism in rats during the effector phase of collagen-induced arthritis (CIA).

Methods: CIA was induced in female dark agouti rats. At the clinical onset of CIA, rats were assigned to treatment with vehicle or single subcutaneous doses of ZA (1.

Reduced arterial elasticity in rheumatoid arthritis and the relationship to vascular disease risk factors and inflammation.

Objective: Rheumatoid arthritis (RA) is associated with increased rates of cardiovascular disease. Reduced small artery elasticity (SAE) and large artery elasticity (LAE) and increased systemic vascular resistance (SVR) have been found in other high-risk groups. In the present study, we sought to determine whether arterial elasticity was reduced and SVR was increased in RA patients compared with controls matched for coronary artery disease (CAD) status, and to relate the results to vascular disease risk factors, including measures of inflammation.

Osteoprotegerin reduces osteoclast numbers and prevents bone erosion in collagen-induced arthritis.

Rheumatoid arthritis is characterized by progressive synovial inflammation and joint destruction. While matrix metalloproteinases (MMPs) are implicated in the erosion of unmineralized cartilage, bone destruction involves osteoclasts, the specialized cells that resorb calcified bone matrix. RANK ligand (RANKL) expressed by stromal cells and T cells, and its cognate receptor, RANK, were identified as a critical ligand-receptor pair for osteoclast differentiation and survival.

Involvement of receptor activator of NFkappaB ligand and tumor necrosis factor-alpha in bone destruction in rheumatoid arthritis.

Bone loss represents a major unsolved problem in rheumatoid arthritis (RA). The skeletal complications of RA consist of focal bone erosions and periarticular osteoporosis at sites of active inflammation, and generalized bone loss with reduced bone mass. New evidence indicates that osteoclasts are key mediators of all forms of bone loss in RA.

Expression of osteoclast differentiation factor at sites of bone erosion in collagen-induced arthritis.

Objective: To investigate the cellular mechanism of bone destruction in collagen-induced arthritis (CIA).

Methods: After induction of CIA in DA rats, a histologic study of the advanced arthritic lesion was carried out on whole, decalcified joints from the hindpaws of affected animals. To conclusively identify osteoclasts, joint tissue sections were stained for tartrate-resistant acid phosphatase (TRAP) enzyme activity, and calcitonin receptors (CTR) were identified using a specific rabbit polyclonal antibody.

Activated T lymphocytes support osteoclast formation in vitro.

Osteoblastic stromal cells are capable of supporting osteoclast formation from hematopoietic precursors in the presence of osteotropic factors such as 1alpha,25(OH)(2)D(3), PTH, and IL-11. Osteoblastic stromal cells produce receptor activator of NF-kappaB ligand (RANKL), a type II membrane protein of the TNF ligand family, in response to these agents. Activated T lymphocytes also produce RANKL; however, the ability of this cell type to support osteoclast formation in vitro is unknown.