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ID PMID Title PublicationDate abstract
16487461 Total ankle arthroplasty with the Agility prosthesis: clinical and radiographic evaluation 2006 Feb BACKGROUND: Although ankle arthrodesis remains a standard operative procedure for disabling ankle arthritis, it has potential long-term problems. Total ankle arthroplasty offers preserved joint motion and may be a more favorable option in select patients. The purpose of this study was to report the intermediate-term clinical and radiographic results of total ankle arthroplasty using the Agility prosthesis. METHODS: We retrospectively reviewed the results of total ankle arthroplasty in 41 consecutive patients (43 ankles). Evaluation included preoperative and postoperative questionnaires, physical examination, and radiographs. RESULTS: At the time of followup, 38 patients (40 ankles) were available for review. The most common preoperative diagnoses included posttraumatic arthritis (24 of 40 ankles, 60%) and rheumatoid arthritis (eight of 40 ankles, 20%). Average age at surgery was 63 (range 32 to 85) years. Average followup was 44.5 (range 26 to 64) months. Preoperative and postoperative American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scores averaged 33.6 and 83.3, respectively, demonstrating significance (p < 0.001). Postoperative Medical Outcomes Study Short Form-36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores averaged 49.5 and 56.1, respectively. Although 34 of 40 ankles demonstrated radiographic lucency or lysis, the degree of involvement varied. Migration or subsidence of components was noted in 18 ankles. Overall, 37 of 38 patients were satisfied with the outcome of their surgery and would have the same procedure under similar circumstances. CONCLUSIONS: Agility total ankle arthroplasty results in a favorable clinical outcome and patient satisfaction in most patients at intermediate-term followup. However, total ankle arthroplasty is associated with potential complications and the need for subsequent operative intervention. Radiographic followup commonly reveals periprosthetic lucency, lysis, and component migration or subsidence, but this does not appear to adversely affect the intermediate-term clinical outcome. The long-term consequences of such radiographic findings are of concern, and surgeons and patients choosing this procedure need to be cautious.
16766366 Preferential immunoglobulin oxidation in children with juvenile idiopathic arthritis. 2006 May OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a rare chronic inflammatory disorder of the joints. There is strong evidence that oxidative damage occurs in rheumatoid diseases, including JIA. The increased level of protein oxidation products in total plasma proteins has recently been reported in children with diagnosed JIA. The objective of this study was to find out which fraction of plasma proteins is mostly damaged by oxidative stress and whether the damaging effect correlates with certain clinical or laboratory parameters. METHODS: A new approach to estimate the carbonyl content of plasma protein fractions was developed, based on two-stage electrophoresis and immunochemical detection of the carbonyl derivatives of the proteins. This method allowed us to detect and quantitate carbonyl groups in the albumin, alpha-2, beta and gamma-globulin fractions. Sera of 25 children with JIA and 13 healthy controls were tested. RESULTS: Albumin and gamma-globulins were found to be most modified by oxidation. In a group of children with systemic JIA, both albumin and gamma-globulins were oxidized while plasma gamma-globulin fraction damage was prevalent in pauciarticular JIA. CONCLUSIONS: Among plasma proteins of children with JIA, gamma-globulins were preferentially oxidized, whereas most of the other proteins did not seem to be affected. Oxidative modification of plasma proteins was correlated with the type of JIA. These findings may allow the use of carbonyls as clinical markers of inflammatory process activity in patients with different types of JIA. It is also a potential tool for monitoring oxidative protein damage in other diseases and therapies.
16701134 Distal interphalangeal joint arthrodesis with screw fixation: why and how. 2006 May Though DIP joint fusion can be successfully achieved with K-wires in both the osteoarthritic and rheumatoid patient, their use is often some-what of an inconvenience to the patient. They prohibit showering, may become infected, may back out and catch on clothing, and surely slowdown mobilization of the rest of the finger [1]. For optimal prehension, a modest amount of DIP joint flexion is required, however. Thus, one advantage of K-wires is that they allow fusion in 5 degrees to 10 degrees of flexion (Fig. 1). In the rheumatoid patient in particular, bone stock may be so com-promised that getting enough purchase with wires alone can be challenging. Since making the transition to the Herbert screw, hardware-related complications and patient dissatisfaction with obligatory postoperative functional limitations until union is achieved have been eliminated. Despite the fact that the fusion must occur without flexion-a necessity to ensure intramedullary placement of the screw-patients seem to adapt well (Fig. 2). One further potential disadvantage of screw fixation is the issue of size mismatch between phalanx and screw-especially in the small finger. Though cautious insertion is justified, precise technique allows use even in the small finger-a benefit when early motion is indicated; for example, when concomitant proximal interphalangeal (PIP) implant arthroplasty is performed in an adjacent digit. This device is contraindicated, obviously, if future PIP joint arthro-plasty is anticipated in the same finger (Fig. 3).
16678646 Treatment of psoriatic arthritis with etanercept, methotrexate, and cyclosporin A. 2006 Feb BACKGROUND: Psoriatic arthritis (PsA) is seen in approximately 5% to 42% of individuals with psoriasis. CASE SUMMARY: A 37-year-old white male weighing 90 kg presented with erythrodermic psoriasis and PsA. The overall duration of PsA was 3 years. Serum levels of glucose, electrolytes, and tumor markers were normal, as were the results of tests of hepatic and renal function and urinalysis. The findings of posteroanterior radiographic examination of the chest were also normal. However, radiographic examination showed porosis and degeneration in the lumbar vertebrae; narrowing of the L2-L3, L3-L4, and L5-S1 spaces; degenerative changes and narrowing of the proximal interphalangeal and distal interphalangeal (DIP) joints; and osseous ankylosis of the DIP joints of the hands. The cutaneous eruption improved with cyclosporin A (CsA) 3.5 mg/kg p.o., but the severity of PsA did not change. Therefore, parenteral methotrexate (MTX) 15 mg/wk and an indomethacin suppository 100 mg/d were added to the regimen. CsA and MTX were continued for 3 months, during which the patient's PsA symptoms did not abate, based on tender and swollen joint counts, hand-to-floor distance, erythrocyte sedimentation rate, and levels of C-reactive protein (CRP), antistreptolysin O, and rheumatoid factor. Therefore, etanercept 25 mg s.c. twice weekly was added to the regimen. Three weeks after the initiation of this combination, the patient's arthritis had improved. The visual analog scale score decreased from 9 to 4. Tender and swollen joint counts decreased from 28 and 24 to 15 and 10, respectively. The hand-to-floor distance decreased from 20 to 10 cm. The erythrocyte sedimentation rate and levels of CRP, antistreptolysin O, and rheumatoid factor decreased from 72 mm/h, 162 mg/L, 250 IU/mL, and 304 IU/mL at baseline to 23 mm/h, 64 mg/L, 48 IU/mL, and 56.1 IU/mL, respectively. No change was observed in radiographs of the patient's back, hands, and feet. Based on the American College of Rheumatology scoring system, the patient showed 50% improvement in disease severity. Etanercept was discontinued at the end of 4 weeks, and maintenance therapy was continued with MTX alone. No adverse events were reported during or after the completion of etanercept therapy. CONCLUSION: In this patient with PsA that was refractory to CsA and MTX, either alone or in combination, the severity of PsA was reduced after 4 weeks of the combined use of etanercept, CsA, and MTX.
18461057 An endogenous TNF-alpha antagonist induced by splice-switching oligonucleotides reduces in 2008 Jul Tumor necrosis factor-alpha (TNF-alpha) is a key mediator of inflammatory diseases, including rheumatoid arthritis (RA), and anti-TNF-alpha drugs such as etanercept are effective treatments. Splice-switching oligonucleotides (SSOs) are a new class of drugs designed to induce therapeutically favorable splice variants of targeted genes. In this work, we used locked nucleic acid (LNA)-based SSOs to modulate splicing of TNF receptor 2 (TNFR2) pre-mRNA. The SSO induced skipping of TNFR2 exon 7, which codes the transmembrane domain (TM), switching endogenous expression from the membrane-bound, functional form to a soluble, secreted form (Delta7TNFR2). This decoy receptor protein accumulated in the circulation of treated mice, antagonized TNF-alpha, and altered disease in two mouse models: TNF-alpha-induced hepatitis and collagen-induced arthritis (CIA). This is the first report of upregulation of the endogenous, circulating TNF-alpha antagonist by oligonucleotide-induced splicing modulation.
18525112 Citrus nobiletin suppresses bone loss in ovariectomized ddY mice and collagen-induced arth 2007 Bone resorption is known to accelerate during the onset of several disorders, including osteoporosis (OP) and rheumatoid arthritis (RA). Some epidemiological surveys have suggested that a high intake of vegetables and fruits has an inverse relation to such disease incidence, though the number of active constituents elucidated thus far is limited. In the present study, we examined the efficacy of various food phytochemicals using two animal models. First, female ddY mice were ovariectomized (OVX) or sham-operated (sham), after which five different compounds (phenethyl isothiocyanate, zerumbone, auraptene, 1'-acetoxychavicol acetate, and nobiletin) were administered separately to OVX mice with a mini-osmotic pump at doses of 0.25 or 0.5 mg/day for 4 weeks, with 17beta-estradiol (E_{2}, 0.03 microg/day) used as a positive control. Nobiletin, in contrast to the other tested phytochemicals, significantly (P<0.05) suppressed the reduction of whole bone mineral density by 61%, which was comparable to or higher than the efficacy of E_{2}. Next, nobiletin given as an i.p. administration at 20 mg/kg of body weight, but not 2 mg/kg, to male DBA/1J mice every 2 days for 12 days led to a marked decrease in type II collagen-induced arthritis by 45% (P < 0.05). Furthermore, the flavonoid (4-50 microM) attenuated receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclastogenesis of RAW264.7 cells, as detected by tartarate-resistant acid phosphatase activity and microscopic observations. Of note, nobiletin also suppressed RANKL-activated extracellular signal-regulated kinase1/2, c-Jun N-terminal kinase1/2, and p38 mitogen-activated protein kinase activities, and thereby regulated the promoter activation of nuclear factor kappaB (NFkappaB) and activator protein-1, key transcription factors for differentiation. Together, our results suggest that nobiletin is a promising phytochemical for the prevention or treatment of osteoclastogenesis-related disorders, including OP and RA, with reasonable action mechanisms.
19235111 Head-supporting sign during reclining: an indication of craniovertebral junction involveme 2008 Nov The craniovertebral (CV) junction can be involved in many diseases, e.g. rheumatoid arthritis, as well as destructive bone pathologies such as tumour and tuberculosis (craniovertebral Pott's disease). While some of these patients present acutely with neck pain and neurological deficits, in others the signs and symptoms may be more subtle. Two patients with CV junction involvement are described. One patient suffered from fracture of the anterior arch of atlas after being involved in a motor vehicle accident and the other had craniovertebral Pott's disease. A detailed history and clinical examination was carried out paying special attention to the situation when patients attempted to recline or while getting up from a reclining position. Patients were further investigated with imaging studies which focused on the CV junction. It was noted that patients with CV junction involvement frequently support their head while attempting to recline or when getting up from a reclining posture. This head supporting sign may be the sole neurological finding in some patients with involvement of the CV junction.
19122376 [Infliximab for a girl with refractory pyoderma gangrenosum]. 2008 Dec Pyoderma gangrenosum is a rare chronic ulcerative noninfectious disease of the skin. Half of patients are complicated with other autoimmune diseases, most commonly inflammatory bowel disease, Takayasu disease, and rheumatoid arthritis. It has been reported that approximately 4% of them were childhood-onset. The conventional treatments of pyoderma gangrenosum were described as systemic corticosteroids and cyclosporine. The combination of corticosteroids with immunosuppressants such as tacrolimus, mycophenolate mofetil has been reported as steroid-sparing modalities. We herein reported a girl, 12 years of age, having pyoderma gangrenosum refractory to the conventional combination of systemic prednisolone with cyclosporine, but successfully treated with infliximab, the anti-TNFalpha monoclonal antibody. Rapid improvement of pyoderma gangrenosum was seen within three doses of infliximab infusion. All skin lesions eventually healed completely and new skin ulcers were never coming out again. The dramatical improvement suggested that infliximab should be considered for patients with refractory pyoderma gangrenosum though further experiences and investigations are required to determine the mechanism of infliximab.
18991731 Small molecule p38 MAP kinase inhibitors for the treatment of inflammatory diseases: novel 2008 The p38 mitogen-activated protein (MAP) kinase plays a central role in inflammation. It has been the subject of extensive efforts in both basic research and drug discovery for the treatment of inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis, where aberrant cytokine signaling is the driver of the disease. This article reviews the patent and journal publication activities during 2006-2008 describing novel small molecule p38alpha inhibitors.
17606182 Effect sizes can be calculated for studies reporting ranges for outcome variables in syste 2007 Aug OBJECTIVE: To develop a method by which studies reporting the ranges (or maxima and minima) of observed outcomes can be included in systematic reviews, along with other studies reporting in the more usual way by using standard deviations (SDs). STUDY DESIGN AND SETTING: An approach is proposed to allow a numerical conversion of a reported range from a continuous outcome into an equivalent SD. RESULTS: The SD is estimated from the observed range times an appropriate conversion factor. Two examples (the first concerning a patient education program on adherence to drug treatment for rheumatoid arthritis, and the second investigating if cognitive behavior therapy could improve adherence to antiretroviral therapy and then lead to suppression of human immunodeficiency virus replication) demonstrate the calculations. CONCLUSION: This note provides a simple method to allow studies that report outcome variability in terms of ranges to be included in systematic reviews by conversion to equivalent SDs. The method is entirely valid if the outcome variable is normally distributed, but for nonnormal data, some caution may be needed.
17558260 Psychosis and EEG abnormalities as manifestations of Hashimoto encephalopathy. 2007 Jun Hashimoto encephalopathy (HE) is a distinct form of encephalopathy, which can manifest itself with purely psychiatric symptoms. A 38-year-old female with history of rheumatoid arthritis was treated with psychotropic drugs for a couple of years in psychiatric structures because of the onset of depressive symptoms, psychoticlike manifestations, and impairment of cognitive functions. The electroencephalography (EEG) was characterized by general slowing with high voltage (2 to 3 Hz) delta biphasic and triphasic waves. Once a firm diagnosis of HE was made, corticosteroid treatment resulted in resolution of her psychiatric symptoms, marked EEG improvement, and partial improvement in her cognitive functions. HE should be suspected in young females with history of autoimmune disorders and EEG abnormalities.
17296665 Hydroxychloroquine-induced toxic myopathy causing respiratory failure. 2007 Feb Chloroquine and hydroxychloroquine (HCQ) are commonly prescribed antimalarial agents used for a variety of systemic diseases. HCQ neuromyotoxicity is a rare complication characterized by proximal muscle weakness, normal creatinine kinase levels, and characteristic ultrastructural changes on muscle biopsy of curvilinear body formation. In this report, we describe a patient with rheumatoid arthritis and respiratory failure associated with proximal myopathy secondary to HCQ. Characteristic changes on muscle biopsy were present. Patients treated with HCQ in whom proximal myopathy, neuropathy, or cardiomyopathy develop should be evaluated for possible HCQ toxicity. Clinicians should be aware of this unusual complication of antimalarials, as discontinuation of the agent may result in clinical improvement.
18728632 MicroRNAs, the immune system and rheumatic disease. 2008 Oct MicroRNAs (miRNAs) are short noncoding RNA molecules that modulate the expression of multiple target genes at the post-transcriptional level and are implicated in a wide array of cellular and developmental processes. In hematopoietic cells, miRNA levels are dynamically regulated during lineage differentiation and also during the course of the immune response. Mouse models have provided good evidence for miRNAs being key players in the establishment of hematopoietic lineages. Furthermore, miRNA-dependent alterations in gene expression in hematopoietic cells are critical for mounting an appropriate immune response to a wide range of pathogens, spontaneously emerging tumors, and autoimmune cells. Deregulation of hematopoietic-specific miRNA expression results in defects in both central and peripheral tolerance, hematopoietic malignancies, and sometimes both. Abnormal expression of miRNAs-which is implicated in inflammation-has also been found in patients with rheumatoid arthritis. These findings identify miRNAs as critical targets for immunomodulatory drug development.
18539434 Immune deficiency or hyperactivity-Nf-kappab illuminates autoimmunity. 2008 Nov Nuclear factor (NF)-kappaB is a transcription factor family which transmits signals from the cell surface to the nucleus, resulting in transcriptional effects on genes involved in inflammation, cell differentiation and survival. The signaling of NF-kappaB and mitogen-activated protein (MAP) kinases through adapter molecules is of critical importance to survival and activation of all cells in the body, including those regulating innate and adaptive immunity. Here we review the individual and intersecting roles played by the alternate and classical NF-kappaB pathways in the pathogenesis of autoimmune disease. Understanding the differences in classical and alternate NF-kappaB function has greatly assisted the development of models of their contribution to different autoimmune diseases. To exemplify these concepts, we consider the contribution of NF-kappaB to rheumatoid arthritis and type 1 diabetes pathogenesis and approaches to immunotherapy.
23675073 Free radicals, antioxidants in disease and health. 2008 Jun Free radicals and oxidants play a dual role as both toxic and beneficial compounds, since they can be either harmful or helpful to the body. They are produced either from normal cell metabolisms in situ or from external sources (pollution, cigarette smoke, radiation, medication). When an overload of free radicals cannot gradually be destroyed, their accumulation in the body generates a phenomenon called oxidative stress. This process plays a major part in the development of chronic and degenerative illness such as cancer, autoimmune disorders, aging, cataract, rheumatoid arthritis, cardiovascular and neurodegenerative diseases. The human body has several mechanisms to counteract oxidative stress by producing antioxidants, which are either naturally produced in situ, or externally supplied through foods and/or supplements. This mini-review deals with the taxonomy, the mechanisms of formation and catabolism of the free radicals, it examines their beneficial and deleterious effects on cellular activities, it highlights the potential role of the antioxidants in preventing and repairing damages caused by oxidative stress, and it discusses the antioxidant supplementation in health maintenance.
18466446 A likelihood-based procedure for obtaining confidence intervals of disease loci with gener 2007 We proposed a confidence interval method for disease gene localization by testing every position on each chromosome of interest for its possibility of being a disease locus and including those not rejected into the interval. Three test statistics were proposed to perform the tests, including one based on LOD and two generalized likelihood ratio tests with or without model averaging (GLRT/MA and GLRT). For the statistic based on LOD, an integrated procedure was proposed with an adaptive and an importance sampling component. We also proposed asymptotic approaches based on GLRT and GLRT/MA as alternatives that are much more efficient computationally but depends on the reliability of the limiting distributions. Besides its efficiency, the asymptotic procedure based on GLRT/MA also takes model uncertainty into consideration. Applications of these methods to the Genetic Analysis Workshop 15 (GAW15) rheumatoid arthritis data from the French population gave results that successfully captured the well recognized susceptibility gene HLA*DRB1 to a less than 6 cM, 99% confidence interval with the two asymptotic approaches.
18368274 Chagas disease as a mechanistic model for testing a novel hypothesis. 2008 Jan The association between depression and cardiovascular disease is well documented. Nevertheless, the process through which they are linked remains unknown, as does the direction of this relationship. Studies have suggested both that depression is a risk factor for heart disease and that heart disease is a risk factor for depression. A number of studies have established that a relationship exists between depression and inflammation, with alterations in the levels of inflammatory markers (IL-1, IL-6, TNF-alpha and others). Depressive symptoms have also been identified in many diseases characterized by inflammatory processes e.g. rheumatoid arthritis, bronchial asthma, diabetes, tuberculosis and cardiovascular diseases. In this brief viewpoint, we explain and propose how to use Chagas disease, a disorder characterized by inflammatory processes and leading to cardiovascular and autonomic problems, as a model for studying the directionality of the relationship between heart disease and depression.
17927684 Toll-like receptor 4 (TLR4) gene polymorphisms in celiac disease. 2007 Dec Toll-like receptors (TLRs) participate in the first line of immune defense through antigen pattern recognition, and ligands include exogenous and host-derived molecules. Coding variants in TLR4 have been associated with autoimmune diseases like ulcerative colitis, Crohn's disease, and rheumatoid arthritis. Our aim was to determine whether these polymorphisms are associated with celiac disease (CD). Two coding single nucleotide polymorphisms of TLR4 (Asp299Gly and Thr399Ile) were genotyped in 95 family trios with CD as well as in 186 patients and 186 unrelated controls. There were no differences in allele, genotype or haplotype distribution, or transmission between patient and control groups. Our results do not support association of these TLR4 variants with CD.
17907590 Are women appropriately represented and assessed in clinical trials submitted for marketin 2007 Sep OBJECTIVE: There is concern that patients included in trials do not represent the true patient population and women in particular may selectively be excluded. We looked at trial data submitted to the European Medicines Agency (EMEA) by drug companies to achieve marketing authorization in Europe between 2000 and 2003. METHODS: We reviewed the EMEA database and included the main studies for the risk/benefit assessment (pivotal trials) submitted between 2000 and 2003. RESULTS: In pivotal trials submitted to the EMEA there was no, or generally clinically negligible, evidence for gender bias; however, women were underrepresented in hypertension, diabetes and hepatitis B trials, and overrepresented in rheumatoid arthritis and allergic conjunctivitis. CONCLUSIONS: In trials submitted for marketing authorization to the EMEA gender bias was not a serious problem.
17659485 Targeting effector memory T-cells with Kv1.3 blockers. 2007 Jul After initially being pursued for general immunosuppression, the voltage-gated potassium channel Kv1.3 has more recently emerged as an attractive pharmacological target for the selective suppression of CCR7- effector memory T-cells in T-cell mediated autoimmune diseases such as multiple sclerosis, type 1 diabetes, rheumatoid arthritis and psoriasis. This article gives a brief summary of the role of Kv1.3 in autoimmune diseases, reviews the progress made in both developing peptidic and small-molecule inhibitors for this challenging target, and in validating Kv1.3 as a target for the treatment of autoimmune diseases.