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ID PMID Title PublicationDate abstract
21833572 Stable reconstruction using halo vest for unstable upper cervical spine and occipitocervic 2012 Feb INTRODUCTION: Upper cervical or occipitocervical disorders such as rheumatoid arthritis present as atlantoaxial subluxation, vertical subluxation of the axis, and subaxial subluxation, which produce myelopathy and severe pain. In such cases, occipitocervical reconstruction surgery may be indicated, and several reports have described reduction of subluxation by fixing the halo vest before this surgery. PURPOSE: The purpose of this study was to evaluate the efficacy of using the halo vest before the surgery for unstable upper cervical spine and for occipitocervical instability. METHODS: Twenty-eight patients (9 men and 19 women; mean age, 61.8 years at surgery) who presented with atlantoaxial or occipitocervical fusion were studied. In all cases, the halo vest was fixed in the conscious condition, and subluxation was reduced before the surgery. The mean follow-up period was 45 months. Roentgenologic measurement and clinical evaluation were performed before the surgery and at the final follow-up. RESULTS: Using the halo vest resulted in significant reductions in the atlantodental interval, the space available for the spinal cord, and the Ranawat value (p < 0.05), and these were maintained until the final follow-up. The mean Japanese Orthopedic Association score significantly improved from 9.5 before surgery to 12.2 at the final follow-up (p = 0.01). Nineteen cases (68%) improved by more than 1 grade by Ranawat's classification after surgery and 16 cases (57%) maintained the same at the follow-up visit. CONCLUSION: Conscious preoperative reduction using the halo vest for occipitocervical disorders is a useful and safe technique.
21813547 EULAR recommendations for vaccination in paediatric patients with rheumatic diseases. 2011 Oct Evidence-based recommendations for vaccination of paediatric patients with rheumatic diseases (PaedRD) were developed by following the EULAR standardised procedures for guideline development. The EULAR task force consisted of (paediatric) rheumatologists/immunologists, one expert in vaccine evaluation, one expert in public health and infectious disease control, and one epidemiologist. A systematic literature review was conducted in MEDLINE, EMBASE, and abstracts of the EULAR and American College of Rheumatology meetings of 2008/9. The level of evidence and strength of recommendation were based on customary scoring systems. Delphi voting was applied to assess the level of agreement between task force members. 107 papers and eight abstracts were used. The majority of papers considered seasonal influenza (41) or pneumococcal (23) vaccination. 26 studies were performed specifically in paediatric patients, and the majority in adult rheumatoid arthritis and systemic lupus erythematosus patients. Fifteen recommendations were developed with an overall agreement of 91.7%. More research is needed on the safety and immunogenicity of (live-attenuated) vaccination in PaedRD, particularly in those using biologicals, and the effect of vaccination on prevention of infections.
21789372 Translation, cultural adaptation and reproducibility of the Cochin Hand Functional Scale q 2011 OBJECTIVE: To translate, to perform a cultural adaptation of and to test the reproducibility of the Cochin Hand Functional Scale questionnaire for Brazil. METHODS: First, the Cochin Hand Functional Scale questionnaire was translated into Portuguese and was then back-translated into French. These translations were reviewed by a committee to establish a Brazilian version of the questionnaire to be tested. The validity and reproducibility of the Cochin Hand Functional Scale questionnaire was evaluated. Patients of both sexes, who were aged 18 to 60 years and presented with rheumatoid arthritis affecting their hands, were interviewed. The patients were initially interviewed by two observers and were later interviewed by a single rater. First, the Visual Analogue Scale for hand pain, the Arm, Shoulder and Hand Disability questionnaire and the Health Assessment Questionnaire were administered. The third administration of the Cochin Hand Functional Scale was performed fifteen days after the first administration. Ninety patients were assessed in the present study. RESULTS: Two questions were modified as a result of the assessment of cultural equivalence. The Cronbach's alpha value for this assessment was 0.93. The intraclass intraobserver and interobserver correlation coefficients were 0.76 and 0.96, respectively. The Spearman's coefficient indicated that there was a low level of correlation between the Cochin Hand Functional Scale and the Visual Analogue Scale for pain (0.46) and that there was a moderate level of correlation of the Cochin Scale with the Health Assessment Questionnaire (0.66) and with the Disability of the Arm, Shoulder and Hand questionnaire (0.63). The average administration time for the Cochin Scale was three minutes. CONCLUSION: The Brazilian version of the Cochin Hand Functional Scale was successfully translated and adapted, and this version exhibited good internal consistency, reliability and construct validity.
21763363 Cloning, expression, purification and characterization of a single chain variable fragment 2011 Dec 20 Anti TNF-α molecules have been used as therapeutic agents in a variety of human diseases such as Rheumatoid arthritis, Ankylosing spondylitis, Chron's diseases, Psoriasis, etc., where high levels of TNF-α plays a destructive role. The limitations of the present TNF-α inhibitors in terms of size, tissue penetration and immunogenicity, etc., provoked the search for small anti TNF-α molecules. In the present study, a single chain variable fragment (ScFv) construct was made from a monoclonal antibody of the class IgG raised against TNF-α was used. The anti TNF-α ScFv was well expressed as soluble form in Escherichia coli BL21 (DE3), which was purified to homogeneity by commercial methacrylate monolith-convective interaction media (CIM) supports using two different chemistries, immobilized metal affinity chromatography (IMAC) with copper ions followed by anion exchange chromatography. The anti TNF-α ScFv found to be inhibiting the TNF-α mediated cytotoxicity in MCF-7 cells with an IC(50) of 8μg. Data presented here are promising and encouraging to further optimize anti TNF-α ScFv production in larger scale with higher recovery at a cheaper price for therapeutic purposes.
21701768 A glycoprotein from Porphyra yezoensis produces anti-inflammatory effects in liposaccharid 2011 Nov The purpose of this study was to investigate the antioxidant and anti-inflammatory effects of a glycoprotein isolated from the alga Porphyra yezoensis in LPS-stimulated RAW 264.7 mouse macrophages. First, we extracted a novel material with antioxidant activity from P. yezoensis, confirmed by SDS-PAGE to be a glycoprotein, which we named P. yezoensis glycoprotein (PGP). PGP inhibited the production of NO and ROS and expression of iNOS, COX-2, TNF-α and IL-1β, which are involved in the pathogenesis of many inflammation-associated human diseases, including septic shock, hemorrhagic shock and rheumatoid arthritis. Next, we determined the mechanisms behind the antioxidant and anti-inflammatory activities of PGP. We focused on the Toll-like receptor 4 (TLR4) signaling pathway because it is well-known to induce the pro-inflammatory proteins that trigger MAPK and NF-κB activation in lipopolysaccharide (LPS)-induced oxidative events. PGP treatment reduced the formation of the TLR4-IRAK4 and TLR4-TRIF binding complexes in response to LPS. Moreover, it inhibited LPS-induced activation and nuclear translocation of NF-κB by abrogating IκB phosphorylation. PGP also suppressed the phosphorylation of ERK1/2 and JNK in a dose-dependent manner. These results suggest that PGP exerts its anti-inflammatory effects by modulating TLR4 signaling and thus inhibiting the activation of NF-κB and MAP kinases.
21584421 Brazilian biologic registry: BiobadaBrasil implementation process and preliminary results. 2011 Mar OBJECTIVES: The present study aimed at describing the implementation process of a national registry in a developing country (Brazil) and at reporting the main preliminary results of the BiobadaBrasil registry. MATERIAL AND METHODS: Through a PANLAR agreement, the Biobadaser protocol was used as a model for implementing the new registry in our country. During the first two years of this effort, the original protocol was adapted, translated, and presented to all Brazilian rheumatologists. For ten months, data of 1,037 patients (750 subjects treated with biological drugs and 287 control subjects) from 15 centers were collected. RESULTS: Most patients had rheumatoid arthritis (RA) (n = 723). Infliximab was the most frequently used anti-TNF agent, and the total exposure to biologic drugs was 2,101 patient-years. The most common reason for interrupting drug use was lack or loss of efficacy (50%), while 30% withdrew from the treatment arm due to adverse events. Three cases of tuberculosis were observed in the biologic group, with an incidence higher than that of the general Brazilian population. Infections were observed in 23% of the biologic group, and the upper respiratory tract was the most commonly affected site. Only one case of tuberculoid leprosy was observed. No deaths or malignancies attributed to drug effects were observed as of February 2010. CONCLUSIONS: The implementation of the BiobadaBrasil registry was successful, and, although recent, the registry has provided important data.
21415679 Complications of hip arthroscopy in children and adolescents. 2011 Apr BACKGROUND: Hip arthroscopy has become an established procedure for certain hip disorders. Complications of hip arthroscopy have been characterized in adult populations, but complications in children and adolescents have not been well described. The purpose of this study was to characterize complications of hip arthroscopy in children and adolescents. METHODS: The study design was a retrospective review of 218 hip arthroscopies in 175 patients aged 18 years old and younger over a 9-year period by a single surgeon at a tertiary-care children's hospital. Patient demographics, indications for surgery, and complications after surgery were recorded. Indications for surgery included: isolated labral tear (n=131), labral tear with concomitant hip disorder (n=37), Perthes disease (n=10), hip dysplasia (n=5), juvenile rheumatoid arthritis (n=3), loose bodies (n=3), osteochondral fracture (n=3), synovitis (n=2), avascular necrosis (n=1), chondral lesion (n=1), iliopsoas tendinitis (n=1), and slipped capital femoral epiphysis (n=1). RESULTS: The overall complication rate in the study population was 1.8%. Complications of arthroscopy included: transient pudendal nerve palsy (n=2), instrument breakage (n=1), and suture abscess (n=1). No cases of proximal femoral physeal separation, osteonecrosis, or growth disturbance were noted. CONCLUSIONS: Hip arthroscopy in children and adolescents seems to be a safe procedure with a low complication rate similar to adults. LEVEL OF EVIDENCE: IV (case series).
21393872 Liver pathology in collagen vascular disorders highlighting the vascular changes within po 2011 Jan BACKGROUND: Collagen vascular disorders (CVDs) are autoimmune disorders with multisystem involvement. Clinical liver involvement is not a characteristic feature though histological involvement could be frequent. Liver disease in CVDs could be the consequence of various factors. AIM: The aim was to analyze the histological spectrum of liver in collagen vascular disorders (CVDs) at autopsy. MATERIALS AND METHODS: Thirty-six autopsy livers negative for hepatitis B or C virus were studied in CVD cases with no known association with chronic liver disease or vascular thrombosis or hematological disorder. Cirrhotic and normal livers were used as controls. The paired t-test, one-way ANOVA, and two-sided Dunnett t-test were used for comparison (< 0.05). None of the control cases showed any abnormal vessels. RESULTS: There were 21 systemic lupus erythematosus (SLE), 7 rheumatoid arthritis (RA), 5 systemic sclerosis (SSc), and 3 polyarteritis nodosa (PAN) cases (M:F = 11:25, age range 23-60 years). HISTOLOGY: Diffuse nodular regenerative hyperplasia of liver (NRHL) was seen in 10 cases, and 6 (5 SLE and 1 RA) had numerous abnormal thin-walled vessels in intermediate- and small-sized portal tracts with no vascular occlusion or inflammation. Moderate sized portal tracts showed more interface and lobular inflammation. The main portal vein and its major branches were normal. None of these six cases had increased transmainases (P>0.05). Most SLE cases had increased transaminases (P<0.05). No evidence of portal hypertension was seen in all except in one RA. Septicemia is known to be associated with raised transaminases. CONCLUSION: A rare pathology of conglomerate of abnormal vessels in intermediate- and small-sized portal system was observed co-existing with NRHL in CVDs. Raised liver enzyme with interface hepatitis in CVD may not necessarily warrant an overlap, as a similar feature could be observed in septicemia.
20641300 (111)In-TA138. 2004 Integrins are a family of cell surface heterodimeric glycoproteins that mediate diverse biological events involving cell-cell and cell-matrix interactions (1). They consist of an α and a β subunit and are important for cell adhesion and signal transduction. The α(v)β(3) integrin is the most prominent receptor class affecting tumor growth, tumor invasiveness, metastasis, tumor-induced angiogenesis, inflammation, osteoporosis, and rheumatoid arthritis (2-7). The α(v)β(3) integrin is strongly expressed on tumor cells, activated endothelial cells (3), and arterial smooth muscle cells (8). In contrast, expression of α(v)β(3) integrin is weak on resting endothelial cells and most normal tissues. The α(v)β(3) antagonists are being studied as anti-tumor and anti-angiogenic agents (4, 9, 10), and the agonists are being studied as angiogenic agents for coronary angiogenesis (11, 12). A tripeptide sequence consisting of Arg-Gly-Asp (RGD) was identified as a recognition motif used by extracellular matrix proteins (vitronectin, fibrinogen, laminin, and collagen) to bind to a variety of integrins including α(v)β(3). Various radiolabeled antagonists and peptides were introduced for imaging of tumors and tumor angiogenesis (13). TA138, an antagonist to the α(v)β(3) integrin, was developed based on SH066 (a quinolone-based vitronectin receptor antagonist) (14). TA138 contains a DOTA moiety for (111)In labeling. (111)In-TA138 (RP748) was found to have a high accumulation in a spontaneous mammary adenocarcinoma (α(v)β(3)-positive) in the c-Neu Oncomouse model (14, 15). The binding of (111)In-TA138 to the integrin receptor was found to be specific both in vitro and in vivo.
21331532 Moxibustion for rheumatic conditions: a systematic review and meta-analysis. 2011 Jul Moxibustion, an acupuncture-like intervention, is increasingly used in the management of rheumatic conditions. The aim of this review is to summarize and critically evaluate the trials testing effectiveness of moxibustion for major rheumatic conditions. Fourteen databases were searched from their inception through May 2010, without language restriction. Randomized clinical trials (RCTs) were included if moxibustion was used as the sole treatment or as a part of a combination therapy with conventional drugs for rheumatic conditions. Cochrane criteria were used to assess the risk of bias. A total of 14 RCTs met our inclusion criteria. All were of low methodological quality. The meta-analysis of the eight RCTs suggested favorable effects of moxibustion on the response rate compared with conventional drug therapy [n = 631; relative risk (RR), 1.13; 95% confidence intervals (CIs), 1.02 to 1.26; P = 0.02] with high heterogeneity (I (2) = 58%). A subgroup analysis showed significant effects of moxibustion on the RR compared with drug therapy in patients with knee osteoarthritis, whereas it failed to do so in rheumatoid arthritis. The results of meta-analysis of the six RCTs suggested favorable effects of moxibustion plus drug therapy on the response rate compared with conventional drug therapy alone (n = 433; RR, 1.25; 95% CIs, 1.09 to 1.43; P = 0.02) with high heterogeneity (I (2) = 62%). This systematic review fails to provide conclusive evidence for the effectiveness of moxibustion compared with drug therapy in rheumatic conditions. The total number of RCTs included in this review and their methodological quality were low. These limitations make it difficult to draw firm conclusions.
21278157 TNF receptor II fusion protein with tandemly repeated Fc domains. 2011 Mar The extracellular domain of tumour necrosis factor (TNF) receptor II fused with the human IgG1 Fc region (TNFRII-Fc), as well as antibodies against TNF, has been used to treat rheumatoid arthritis. However, TNFRII-Fc is less effective than these antibodies in terms of antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against cells bearing TNF on the cell surface. We hypothesized that these activities could be increased by fusing TNFRII with tandemly repeated Fc (TNFRII-Fc-Fc). The affinities of TNFRII-Fc-Fc for soluble TNF-α and transmembrane TNF-α and the TNF-α cytotoxicity-inhibitory activity were as potent as those of TNFRII-Fc. TNFRII-Fc-Fc showed much higher binding avidity for Fcγ receptors than TNFRII-Fc and was more potent in terms of both ADCC and CDC against cells expressing transmembrane TNF-α. TNFRII-Fc-Fc of 80 kDa, as well as TNFRII-Fc-Fc of 200 kDa, was detected. TNFRII-Fc-Fc (80 kDa) was as potent as TNFRII-Fc in terms of both ADCC and CDC. These results suggest that Fc multimerization of receptor-Fc fusion proteins can augment effector functions such as ADCC and CDC, and thereby have the potential to provide a superior therapeutic effect. This may be the case not only for TNFRII-Fc but also for other receptor-Fc fusion proteins.
21145999 Denosumab and bisphosphonates: different mechanisms of action and effects. 2011 Apr 1 To treat systemic bone loss as in osteoporosis and/or focal osteolysis as in rheumatoid arthritis or periodontal disease, most approaches target the osteoclasts, the cells that resorb bone. Bisphosphonates are currently the most widely used antiresorptive therapies. They act by binding the mineral component of bone and interfere with the action of osteoclasts. The nitrogen-containing bisphosphonates, such as alendronate, act as inhibitors of farnesyl-pyrophosphate synthase, which leads to inhibition of the prenylation of many intracellular signaling proteins. The discovery of RANKL and the essential role of RANK signaling in osteoclast differentiation, activity and survival have led to the development of denosumab, a fully human monoclonal antibody. Denosumab acts by binding to and inhibiting RANKL, leading to the loss of osteoclasts from bone surfaces. In phase 3 clinical studies, denosumab was shown to significantly reduce vertebral, nonvertebral and hip fractures compared with placebo and increase areal BMD compared with alendronate. In this review, we suggest that the key pharmacological differences between denosumab and the bisphosphonates reside in the distribution of the drugs within bone and their effects on precursors and mature osteoclasts. This may explain differences in the degree and rapidity of reduction of bone resorption, their potential differential effects on trabecular and cortical bone, and the reversibility of their actions.
21060991 Prevalence of vertebral fractures on chest radiographs of elderly African American and Cau 2011 Aug The prevalence of vertebral fractures on routine chest radiographs of elderly Caucasian women was only 1.3 times higher than in African American (AA) women, a difference considerably smaller than reported in population studies. AAs with medical problems may have higher risk of vertebral fractures than previously suspected. INTRODUCTION: Earlier studies noted a 1.9- to 3.7-fold higher prevalence of vertebral fractures in Caucasian (CA) compared to African American (AA) women. These studies, however, may have suffered from selection bias. We reported that among women referred for bone density testing, the prevalence of vertebral fractures in AA was the same as in CA women. Suspecting that the latter might have been due to a referral bias, we examined the racial difference in the prevalence of vertebra fractures on chest radiographs of patients seeking general medical care, not selected for osteoporosis. METHODS: Consecutive chest radiographs (N = 1,200) of women over age 60 were evaluated using Genant's semi-quantitative method. Patients' race and the presence of diseases or medications associated with increased fracture risk were ascertained from the electronic medical records. RESULTS: Among 1,011 women (76% AA) with usable radiographs, 11% had moderate or severe vertebral fractures. The prevalence of vertebral fractures was 10.3% in 773 AA and 13% in 238 CA women (p = 0.248 for difference between races). The lack of difference persisted after controlling for age, smoking, use of glucocorticoids, or presence of cancer, rheumatoid arthritis, organ transplantation, and end-stage renal disease. Among all subjects, CA women were more likely to be diagnosed and treated for osteoporosis (p <0.001). CONCLUSION: Among subjects seeking medical care, the difference in the prevalence of vertebral fractures between AA and CA women is smaller than previously suspected. Greater attention to the detection of vertebral fractures and the management of osteoporosis is warranted in AA women with medical problems.
21059888 Pharmacokinetic-pharmacodynamic modeling of apratastat: a population-based approach. 2011 Apr Apratastat is an orally active, potent, and reversible dual inhibitor of tumor necrosis factor-α converting enzyme (TACE) and matrix metalloproteinases (MMPs). This study characterizes the pharmacodynamic (PD) effect of apratastat following oral administration on tumor necrosis factor-alpha (TNF-α) release. Data were obtained from 3 clinical studies carried out in healthy subjects. Apratastat was administered orally in these studies as single doses or multiple doses (twice daily). The inhibition of TNF-α release by apratastat was investigated in studies of in vitro, ex vivo, and in vivo. Inhibitory E(max) models were used to characterize the inhibition of TNF-α release in both in vitro and ex vivo studies. Apratastat inhibited TNF-α release with a population mean IC(50) of 144 ng/mL in vitro and of 81.7 ng/mL ex vivo, respectively. The relationship between TNF-α and apratastat plasma concentration in the endotoxin-challenged study in healthy subjects was well characterized by a mechanism-based PD population model with IC(50) of 126 ng/mL. Apratastat can potently inhibit the release of TNF-α in vitro, ex vivo, and in vivo. Even though the dosage provided adequate exposure to inhibit TNF-α release, apratastat was not efficacious in rheumatoid arthritis (RA). This inconsistency between TNF-α inhibition and the clinical response requires further investigation.
22894814 Factor H autoantibodies and deletion of Complement Factor H-Related protein-1 in rheumatic 2012 Aug 15 INTRODUCTION: Complement activation is involved in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and atypical hemolytic uremic syndrome (aHUS). Autoantibodies to complement inhibitor factor H (FH), particularly in association with deletions of the gene coding for FH-related protein 1 (CFHR1), are associated with aHUS. METHODS: Autoantibodies against FH, factor I (FI) and C4b-binding protein (C4BP) were measured by ELISA, while CFHR1 homozygous deletion was determined with Western blotting of sera. Epitopes for FH autoantibodies were mapped using recombinant fragments of FH. RESULTS: FH autoantibodies were detected in SLE (6.7%, n = 60, RA patients (16.5%, n = 97 in the Swedish cohort and 9.2%, n = 217 in the Dutch cohort) and thrombosis patients positive for the lupus anticoagulants (LA+) test (9.4%, n = 64) compared with aHUS patients (11.7%, n = 103). In the control groups (n = 354), an average of 4% of individuals were positive for FH autoantibodies. The frequencies observed in both RA cohorts and LA+ patients were statistically significantly higher than in controls. We also found that an average of 15.2% of the FH-autoantibody positive individuals in all studied disease groups had homozygous deficiency of CFHR1 compared with 3.8% of the FH autoantibody negative patients. The levels of FH autoantibodies varied in individual patients over time. FH autoantibodies found in LA+, SLE and RA were directed against several epitopes across FH in contrast to those found in aHUS, which bound mainly to the C-terminus. Autoantibodies against FI and C4BP were detected in some patients and controls but they were not associated with any of the diseases analyzed in this study. CONCLUSIONS: Autoantibodies against FH are not specific for aHUS but are present at a significant frequency in rheumatic diseases where they could be involved in pathophysiological mechanisms.
22235047 Systemic lupus erythematosus following HPV immunization or infection? 2012 Feb BACKGROUND AND PURPOSE: The link between autoimmunity and infectious agents has been strongly suggested by reports of lupus or lupus-like syndromes following immunization. This report describes three patients with either newly diagnosed systemic lupus erythematosus (SLE) or SLE flare, following vaccination for human papilloma virus (HPV). CASE 1: A 17-year-old female completed two doses of HPV vaccine uneventfully. Two months later, she developed arthralgias with pruritic rashes on both lower extremities, later accompanied by livedo reticularis, bipedal edema with proteinuria, anemia, leucopenia, hypocomplementemia and high titers of anti-nuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA). Kidney biopsy showed International Society of Nephrology/Renal Pathology Society Class III lupus nephritis. She was started on high dose steroids followed by pulse cyclophosphamide therapy protocol for lupus nephritis, and subsequently went into remission. CASE 2: A 45-year-old housewife, previously managed for 11 years as having rheumatoid arthritis, had been in clinical remission for a year when she received two doses of HPV immunization. Four months later, she developed fever accompanied by arthritis, malar rash, oral ulcers, recurrent ascites with intestinal pseudo-obstruction, and behavioral changes. Cranial MRI showed vasculitic lesions on the frontal and parietal lobes. Laboratory tests showed anemia with leucopenia, hypocomplementemia, proteinuria, ANA positive at 1:320, and antibodies against dsDNA, Ro/SSA, La/SSB and histone. She improved following pulse methylprednisolone with subsequent oral prednisone combined with hydroxychloroquine. CASE 3: A 58-year-old housewife diagnosed with SLE had been in clinical remission for 8 years when she received two doses of HPV immunization. Three months later, she was admitted to emergency because of a 1-week history of fever, malar rash, easy fatigability, cervical lymph nodes, gross hematuria and pallor. Laboratory exams showed severe anemia, thrombocytopenia, active urine sediments, and hypocomplementemia. Despite pulse steroid therapy, blood transfusions, intravenous immunoglobulin and aggressive resuscitative measures, she expired a day after hospital admission. SUMMARY: These cases narrate instances of the onset or exacerbation of lupus following HPV immunization suggesting adjuvant-induced autoimmunity. On the other hand, there are reports of higher incidence of HPV infection in SLE, with the infection per se possibly contributing to disease activity. Thus, the benefit of HPV immunization may still outweigh the risk among these individuals.
21792834 AC13, a C-terminal fragment of apolipoprotein A-I, is a candidate biomarker for microscopi 2011 Nov OBJECTIVE: Microscopic polyangiitis (MPA) is necrotizing vasculitis of unknown etiology. We analyzed the serum peptide profile of MPA to find a biomarker for this disease. METHODS: Serum peptides from 33 patients with MPA, 7 with granulomatosis with polyangiitis (Wegener's), 7 with Churg-Strauss syndrome, 6 with giant cell arteritis, and 25 with systemic lupus erythematosus (SLE) were comprehensively analyzed by mass spectrometry. Peptide function on human microvascular endothelial cells (HMVECs) was examined by enzyme-linked immunosorbent assay and real-time polymerase chain reaction. RESULTS: A total of 102 serum peptides were detected from the 78 patients. One of the peptides, peptide 1,523, showed significantly higher ion intensity in MPA (mean ± SD 46.8 ± 39.3 arbitrary units [AU]) than in the other systemic vasculitides (14.1 ± 12.2 AU) (P < 0.05) or in SLE (17.0 ± 12.1 AU) (P < 0.05). In MPA, peptide 1,523 showed significantly higher ion intensity before treatment than 1 week (P < 0.05) and 6 weeks (P < 0.05) after the initiation of treatment. Peptide 1,523 was identified as 13 C-terminal amino acid residues of apolipoprotein A-I (Apo A-I) and was designated "AC13." Validation of AC13 ion intensity using another MPA cohort (n = 14) similarly showed significantly higher ion intensity (90.1 ± 167.9 AU) compared to 14 patients with rheumatoid arthritis (8.6 ± 5.4 AU) (P < 0.01) and 14 healthy subjects (11.8 ± 6.1 AU) (P < 0.01). Serum concentrations of Apo A-I and high-density lipoprotein cholesterol were down-regulated in MPA before treatment and returned to their normal ranges 6 weeks after the initiation of treatment (both P < 0.01). Stimulation of HMVECs with AC13 significantly up-regulated secretion of interleukin-6 (IL-6) (P < 0.05) and IL-8 (P < 0.01). CONCLUSION: AC13, a candidate biomarker for MPA, may be useful for monitoring disease activity and may exacerbate vascular inflammation through up-regulation of proinflammatory cytokines.
21068096 Efficacy of a single ultrasound-guided injection for the treatment of hip osteoarthritis. 2011 Jan BACKGROUND: Intra-articular injection is effective for osteoarthritis, but the best single injection strategy is not known, nor are there established predictors of response. The objectives of this study were to assess and predict response to a single ultrasound-guided injection in moderate to severe hip osteoarthritis. METHODS: 77 hip osteoarthritis patients entered a prospective, randomised controlled trial, randomised to one of four groups: standard care (no injection); normal saline; non-animal stabilised hyaluronic acid (durolane) or methylprednisolone acetate (depomedrone). MAIN OUTCOME MEASURES: Numerical rating scale (NRS 0-10) 'worst pain', Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain/function. Potential predictors of response (including radiographic severity, ultrasound synovitis and baseline symptom severity) were examined using univariate logistic regression analysis and Fisher's exact test. RESULTS: NRS pain, WOMAC pain and function improved significantly for the steroid arm alone. Effect sizes at week 1 were striking: NRS pain 1.5, WOMAC pain 1.9 and WOMAC function 1.3. Outcome Measures in Rheumatoid Arthritis Clinical Trials-Osteoarthritis Research Society responder criteria identified 22 responders (intention-to-treat): steroid 14 (74%; number needed to treat, two); saline, four (21%); durolane, two (11%); and no injection, two (10%; χ(2) test between groups, p<0.001). Corticosteroid arm response was maintained over 8 weeks (summary measures analysis of variance, p<0.002 for NRS pain). Synovitis was a significant predictor of response at weeks 4 and 8 (p<0.05, Fisher's exact test; week 4 OR 16.7, 95% CI 1.4 to 204). CONCLUSIONS: Ultrasound-guided corticosteroid injections are highly efficacious; furthermore synovitis on ultrasound is a biomarker of response to injection.
21453476 Treatment of forefoot problems in older people: study protocol for a randomised clinical t 2011 Mar 31 BACKGROUND: Foot problems in general and forefoot problems in particular can lead to a decrease in mobility and a higher risk of falling. Forefoot problems increase with age and are more common in women than in men. Around 20% of people over 65 suffer from non-traumatic foot problems and 60% of these problems are localised in the forefoot. Little is known about the best way to treat forefoot problems in older people. The aim of this study is to compare the effects of two common modes of treatment in the Netherlands: shoe advice and podiatric treatment. This paper describes the design of this study. METHODS: The study is designed as a pragmatic randomised clinical trial (RCT) with 2 parallel intervention groups. People aged 50 years and over who have visited their general practitioner (GP) with non traumatic pain in the forefoot in the preceding year and those who will visit their GP during the recruitment period with a similar complaint will be recruited for this study. Participants must be able to walk unaided for 7 metres and be able to fill in questionnaires. Exclusion criteria are: rheumatoid arthritis, neuropathy of the foot or pain caused by skin problems (e.g. warts, eczema). Inclusion and exclusion criteria will be assessed by a screening questionnaire and baseline assessment. Those consenting to participation will be randomly assigned to either a group receiving a standardised shoe advice leaflet (n = 100) or a group receiving podiatric treatment (n = 100). Primary outcomes will be the severity of forefoot pain (0-10 on a numerical rating scale) and foot function (Foot Function 5-pts Index and Manchester Foot Pain and Disability Index). Treatment adherence, social participation and quality of life will be the secondary outcomes. All outcomes will be obtained through self-administered questionnaires at the start of the study and after 3, 6, 9 and 12 months. Data will be analysed according to the "intention-to-treat" principle using multilevel level analysis. DISCUSSION: Strength of this study is the comparison between two common primary care treatments for forefoot problems, ensuring a high external validity of this trial. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR2212.
21412605 Low prevalence of reactive PPD prior to infliximab use: comparative study on a population 2011 Jan OBJECTIVE: To identify tuberculosis infection in rheumatic patients on infliximab by use of PPD testing prior to immunobiologic therapy. METHODS: This study comprised 157 patients undergoing infliximab treatment and 734 other patients undergoing laboratory screening for tuberculosis infection originating from several services. The Mantoux technique was used for PPD testing, and an induration of at least 5 mm was considered reactive status. RESULTS: In the infliximab group, 13% of the patients reacted to PPD, while, in the other group, 27% of the patients reacted to PPD (χ² = 13; P = 0.0003). These patients were divided into categories: adults with chronic diseases, PPD reactivity of 22%; and other controls, PPD reactivity of 31%. This shows the heterogeneous response of that population (χ² = 7; P < 0.009). In the infliximab group, subdivided according to pathologies [rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PA)], different reactivity rates were observed, the lowest value occurring among RA patients: (RA x AS: OR = 0.13; CI: 0.03-0.47; χ ² = 12; P = 0.0004) and (RA x PA: OR = 0.16; CI: 0.02-1.04; χ² Yates corrected = 3.6; P = 0.05). The PPD reactivity in the RA subgroup (4%) was also lower as compared with that of the chronic patients group (22%) (OR = 0.16; CI: 0.05-0.49; χ² = 14; P = 0.0002), even when reclassified into four subgroups: rheumatology (OR = 0.19; CI: 0.04-0.72), kidney transplantation (OR = 0.16; CI: 0.05-0.51), infectology (OR = 0.21; CI: 0.05-0.75), and other conditions (OR = 0.13; CI: 0.04-0.44). CONCLUSION: The low prevalence of PPD reaction in this Brazilian population, mainly in chronic patients, with the worst performance among RA patients, showed that the test has limited value for diagnosis of tuberculosis infection in candidates to infliximab therapy.