Leslie Schrieber

Antibodies to apolipoprotein A-I, high-density lipoprotein, and C-reactive protein are associated with disease activity in patients with systemic lupus erythematosus

OBJECTIVE Inflammatory disease activity in patients with systemic lupus erythematosus (SLE) may affect the development of atherosclerosis, contributing to their increased risk of cardiovascular disease (CVD). This process may be mediated by anti-apolipoprotein A-I (anti-Apo A-I), anti-high-density lipoprotein (anti-HDL), and anti-C-reactive protein (anti-CRP) autoantibodies. We undertook this study to examine whether levels of these antibodies rise in association with increased SLE disease activity. METHODS IgG anti-Apo A-I, anti-HDL, and anti-CRP levels were measured in serum from the following groups: 39 patients with persistently high disease activity (British Isles Lupus Assessment Group [BILAG] A or B score) over the previous 2 years, 42 patients with persistently low disease activity (no BILAG A or B scores) over the previous 2 years, 34 healthy controls, 25 individual patients from whom paired samples (at time of disease flare and quiescence) were obtained and compared, 16 patients with newly diagnosed lupus nephritis from whom multiple samples were obtained and who were followed up prospectively for up to 2 years, and 24 patients with SLE who had experienced CVD events. RESULTS Serum levels of IgG anti-Apo A-I, anti-HDL, and anti-CRP were higher in patients with SLE than in controls. Anti-Apo A-I and anti-HDL levels, but not anti-CRP levels, were higher in patients with persistently high disease activity than in those with low disease activity. Mean levels of the 3 autoantibodies in patients who had experienced CVD events lay between the mean levels in the high and low disease activity groups. Only levels of anti-Apo A-I were significantly higher in samples obtained from individual patients during disease flares than in samples obtained during disease quiescence. In the lupus nephritis patients, anti-Apo A-I and anti-HDL levels correlated with serum levels of high avidity IgG anti-double-stranded DNA. CONCLUSION Persistent disease activity is associated with a significant increase in IgG anti-Apo A-I and anti-HDL in patients with SLE.

Patients teach students: partners in arthritis education.

A large metropolitan teaching hospital within The Northern Clinical School, University of Sydney.

Attentional Biases in Chronic Pain Associated With Rheumatoid Arthritis: Hypervigilance or Difficulties Disengaging?

UNLABELLED There is evidence that pain patients demonstrate attentional biases toward some pain-related stimuli (eg, sensory words) and not others (eg, affective words). However, whether individuals in chronic pain caused by rheumatoid arthritis (RA) also demonstrate this bias has not been investigated. Further, within the pain literature, whether these biases reflect hypervigilance or difficulty disengaging from stimuli remains contentious. The present study aimed to determine (a) whether RA patients demonstrate an attentional bias to sensory pain words; and (b) whether this bias is a result of hypervigilance or failure to disengage from the stimuli. RA patients showed a bias toward sensory words and away from threat-related words. The effect for sensory words resulted from slowed performance on incongruent trials (ie, difficulty disengaging), whereas the bias away from threat words resulted from faster responses on incongruent trials (ie, avoidance of threat). The pattern of attention biases in RA patients is very similar to those found in patients with chronic pain. At least in RA, attentional biases appear to be related to a failure to disengage from pain-related words rather than hypervigilance. PERSPECTIVE There is continued debate about whether these biases are caused by hypervigilance toward pain stimuli or difficulty disengaging from pain stimuli. This study shows that in a group of RA patients, attentional biases toward pain are caused by difficulty disengaging rather than hypervigilance.

The endothelium in psoriasis.

Summary This article is a review of the role of the endothelium in psoriasis, with emphasis on angiogenesis and lymphocyte—endothelial interactions.

Isolation and purification of microvascular endothelium from human decidual tissue in the late phase of pregancy

Normal pregnancy demands significant structural and physiologic adaptations of the uterine microvasculature, to facilitate adequate placentation. In pregnancies complicated by pregnancy-associated hypertension (preeclampsia), this process is defective, resulting in a high incidence of intrauterine growth retardation. The microvascular endothelium, a focal point for both initiation and inhibition of coagulation and control of vascular tone, may well contribute to development and aggravation of these abnormalities. We describe a method for isolation, purification, and culture of human decidual endothelial cells from biopsies performed at the time of cesarean section. The separation procedure is technically simple, requires only a small piece of tissue, and takes approximately 2 hours to perform. Some of the unique features of these cells in culture are outlined. This technique will permit the close examination of various aspects of the function of these cells in normal pregnancy, and their comparison with cells from pregnancies complicated by hypertension.

Splendic and renal infarction in systemic lupus erythematosus: Association with anti-cardiolipin antibodies

SummaryA 37-year-old female, known to have systemic lupus erythematosus (SLE) and markedly raised anti-cardiolipin antibody levels in association with the lupus anticoagulant, presented with a symptomatic segmental splenic infarction. There was a past history of cerebral infarction. Abdominal computed tomography (CT) demonstrated the area of splenic infarction, and an asymptomatic right renal infarct. This patient illustrates the unusual occurrence of multiple visceral infarcts, in association with anti-cardiolipin antibodies, complicating SLE.

Antiphospholipid antibodies in systemic lupus erythematosus: Clinical and laboratory associations in 111 patients

SummaryAn enzyme linked immunosorbent assay (ELISA) was used to evaluate the prevalence and disease associations of antibodies to a range of negatively charged phospholipids in 111 patients with systemic lupus erythematosus (SLE). The frequency of one or more isotypes of different antiphospholipid antibodies (APLs) was similar (range 33%–45%). When individual isotypes were considered alone there was considerable variation (range 5%–32%). There were significant associations between thrombosis, thrombocytopenia, and central nervous system (CNS) disease but not abortion with elevated APL. Strong associations were found between raised anti-ds-DNA (Farr assay) and a positive direct Coombs test with raised APL. Thus, APLs are common in SLE and are associated with discrete clinical and laboratory features. However, detection of antibodies to a range of negatively charged phospholipids added little clinically useful information to that obtained by measuring anticardiolipin antibody (ACL) alone. We cannot recommend the use of APLs other than ACL for routine testing.

A Blind Randomized Controlled Trial of Cognitive versus Behavioral versus Cognitive-Behavioral Therapy for Patients with Rheumatoid Arthritis

Background: Despite evidence that cognitive-behavioral therapy (CBT) is effective for rheumatoid arthritis (RA), little is known about which components of therapy are most efficacious. The present study compared the efficacy of CBT with cognitive therapy (CT) and behavioral therapy (BT) for patients with RA. We hypothesized that CBT would be more efficacious on a broader range of outcomes. Methods: Participants (n = 104) with classic or definite RA were randomized to receive one of three active treatments (CBT, CT or BT) or a wait-list control (WLC). Participants were assessed at baseline, post-treatment and 6 months on a range of outcomes. Measures of disease activity, joint function, disability and psychological functioning were included. Results: The results showed that participants who received cognitive components had greater improvements in tender joint counts and C-reactive protein at post-treatment. Those receiving either BT or CT alone improved more on anxiety than CBT or WLC. At 6 months, the three active treatment groups could only be distinguished on tender joints, which favored CT and CBT. Conclusions: CBT did not demonstrate the broader benefits to patients that we expected, nor was there evidence that BT produced effects that were superior to CT alone. CT was superior to at least one of the other two active treatment components on 3 of the 7 outcome measures at post-treatment. Effect sizes for the interventions that included cognitive components were similar to those reported in the literature. These results suggest that CT is an effective treatment for RA and need not necessarily include behavioral strategies.

The 2010 Royal Australasian College of Physicians' policy statement 'Circumcision of infant males' is not evidence based.

Infant male circumcision (MC) is an important issue guided by Royal Australasian College of Physicians (RACP) policy. Here we analytically review the RACPs 2010 policy statement ‘Circumcision of infant males’. Comprehensive evaluation in the context of published research was used. We find that the Statement is not a fair and balanced representation of the literature on MC. It ignores, downplays, obfuscates or misrepresents the considerable evidence attesting to the strong protection MC affords against childhood urinary tract infections, sexually transmitted infections (human immunodeficiency virus, human papilloma virus, herpes simplex virus type 2, trichomonas and genital ulcer disease), thrush, inferior penile hygiene, phimosis, balanoposthitis and penile cancer, and in women protection against human papilloma virus, herpes simplex virus type 2, bacterial vaginosis and cervical cancer. The Statement exaggerates the complication rate. Assertions that ‘the foreskin has a functional role’ and ‘is a primary sensory part of the penis’ are not supported by research, including randomised controlled trials. Instead of citing these and meta‐analyses, the Statement selectively cites poor quality studies. Its claim, without support from a literature‐based risk‐benefit analysis, that the currently available evidence does ‘not warrant routine infant circumcision in Australia and New Zealand’ is misleading. The Statement fails to explain that performing MC in the neonatal period using local anaesthesia maximises benefits, safety, convenience and cost savings. Because the RACPs policy statement is not a fair and balanced representation of the current literature, it should not be used to guide policy. In the interests of public health and individual well‐being, an extensive, comprehensive, balanced review of the scientific literature and a risk‐benefit analysis should be conducted to formulate policy.

High endothelial venule morphology and function are inducible in germ-free mice: A possible role for interferon-γ

Cytokines may facilitate lymphocyte traffic by modulating HEV structure and lymphocyte binding function in accordance with local tissue requirements. This study investigated whether the morphology of HEVs and their lymphocyte binding ligand are altered following antigenic challenge and evaluated the role of IFN-gamma in the induction of such changes. The morphology and lymphocyte binding function of mesenteric LN HEVs of GFM exposed to environmental pathogens were compared to those from GFM and conventional mice. Lymph nodes from all mice had microscopically identifiable HEVs. The morphology of HEVs from GFM was not uniform; many HEVs contained flat endothelial cells with sparse cytoplasm and prominent interendothelial gaps. The number of lymphocytes within the lumen and the HEV wall was low. In contrast, HEVs from GFME and conventional mice were characterized by cuboidal endothelial cells with plentiful cytoplasm and large numbers of lymphocytes in the vessel wall and lumen. There was no delineation of interendothelial cell borders. Lymphocyte binding to HEVs of lymph node sections from GFM was reduced (mean +/- SEM: 1.08 +/- 0.15) compared to that of conventional mice (1.91 +/- 0.20), P less than 0.003. GFME had augmented lymphocyte binding (2.23 +/- 0.26) to levels comparable with those of conventional mice. GFM injected intraperitoneally with IFN-gamma, IFN-alpha beta, or diluent resulted in minor changes in HEV morphology. By contrast, lymphocyte binding to HEV of GFM was more than doubled by the injection of IFN-gamma (1.95 +/- 0.25), P less than 0.01, but not IFN-alpha beta (0.54 +/- 0.07) or the relevant diluent controls (0.89 +/- 0.11, 0.56 +/- 0.06, respectively). It appears that the HEV binding ligand is inducible, and its expression is regulated by at least one immunomodulator, IFN-gamma. Although short-term exposure of HEVs to IFN-gamma influenced HEV function it caused only minor changes in morphology.