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ID PMID Title PublicationDate abstract
18466541 No evidence for multiple loci affecting rheumatoid arthritis risk on chromosome 6p21. 2007 The influence of certain alleles of the HLA-DRB1 locus on risk for rheumatoid arthritis has been well established through linkage and association studies. In addition, other loci in the HLA region on 6p21 may also affect an individual's risk profile. Here, we used a method to detect excess identity-by-descent sharing between affected sib pairs conditional on the observed genotypes at the hypothesized causal locus to test for the presence of additional arthritis risk loci in the linked region. We used affected sib pairs from two different studies. Because the test depends heavily on specifying accurate allele frequency estimates at the proposed causal locus, we used HLA-DRB1 allele frequency estimates from a large, population-based sample. We also discuss an alternate form of the test in which we could condition on parental genotypes, thereby eliminating the need for actual allele frequencies. The test showed no evidence for the presence of additional arthritis risk loci in the region in the British or North American samples made available for Genetic Analysis Workshop 15. Given the prior knowledge that there likely are arthritis risk loci other than HLA-DRB1 in the region, it appears the tests may have inadequate power to detect the presence of these loci in certain cases.
23969923 Arthritis epidemiology impacts pharmacists. 2008 Nov Epidemiologic data indicates that the occurrence of arthritis and related diseases will have a significant impact upon the practice of pharmacy. The two most prevalent diseases are osteoarthritis and rheumatoid arthritis. These two diseases currently affect millions of Americans. Data is presented that facilitate awareness of the need to develop ways to economically provide pharmaceutical care with the expanding epidmeic of rheumatic diseases.
16425898 New drugs for peripheral joint psoriatic arthritis. 2006 Jan Up to 3% of people have psoriasis, and as many as 42% of these have an associated chronic inflammatory arthritis. In up to 20% of such patients, the arthritis progresses to become severe, destructive and deforming. Traditional drug treatments include NSAIDs and disease-modifying anti-rheumatic drugs (DMARDs) used for rheumatoid arthritis. Leflunomide (Arava - Sanofi-Aventis), etanercept (Enbrel - Wyeth) inifliximab (Remicade - Schering-Plough) and adalimumab (Humira - Abbott) are licensed for the treatment of patients with peripheral joint disease in psoriatic arthritis. Here we review drug therapy for such patients, concentrating on the newer agents.
17892600 NF-kappaB inhibitor dehydroxymethylepoxyquinomicin suppresses osteoclastogenesis and expre 2007 Inhibition of NF-kappaB is known to be effective in reducing both inflammation and bone destruction in animal models of arthritis. Our previous study demonstrated that a small cell-permeable NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), suppresses expression of proinflammatory cytokines and ameliorates mouse arthritis. It remained unclear, however, whether DHMEQ directly affects osteoclast precursor cells to suppress their differentiation to mature osteoclasts in vivo. The effect of DHMEQ on human osteoclastogenesis also remained elusive. In the present study, we therefore examined the effect of DHMEQ on osteoclastogenesis using a mouse collagen-induced arthritis model, and using culture systems of fibroblast-like synovial cells obtained from patients with rheumatoid arthritis, and of osteoclast precursor cells from peripheral blood of healthy volunteers. DHMEQ significantly suppressed formation of osteoclasts in arthritic joints, and also suppressed expression of NFATc1 along the inner surfaces of bone lacunae and the eroded bone surface, while serum levels of soluble receptor activator of NF-kappaB ligand (RANKL), osteoprotegerin and macrophage colony-stimulating factor were not affected by the treatment. DHMEQ also did not suppress spontaneous expression of RANKL nor of macrophage colony-stimulating factor in culture of fibroblast-like synovial cells obtained from patients with rheumatoid arthritis. These results suggest that DHMEQ suppresses osteoclastogenesis in vivo, through downregulation of NFATc1 expression, without significantly affecting expression of upstream molecules of the RANKL/receptor activator of NF-kappaB/osteoprotegerin cascade, at least in our experimental condition. Furthermore, in the presence of RANKL and macrophage colony-stimulating factor, differentiation and activation of human osteoclasts were also suppressed by DHMEQ, suggesting the possibility of future application of NF-kappaB inhibitors to rheumatoid arthritis therapy.
18360621 Adalimumab in the treatment of arthritis. 2007 Mar Tumor necrosis factor (TNF) has been implicated in a number of arthritic disease states, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Adalimumab is the first fully human, high-affinity, recombinant immunoglobulin G(1) (IgG(1)) anti-TNF monoclonal antibody. Adalimumab in combination with methotrexate or standard antirheumatic therapies, or as monotherapy, is effective in the treatment of adults with active rheumatoid arthritis who have had an inadequate response to disease-modifying antirheumatic drugs. Adalimumab is also effective in the treatment of patients with moderately to severely active psoriatic arthritis, improving both joint and skin manifestations of the disease as well as disability due to joint damage. In the Adalimumab Trial Evaluating Long-term Efficacy and Safety in Ankylosing Spondylitis (ATLAS), adalimumab significantly reduced the signs and symptoms of active ankylosing spondylitis and established a sustained clinical response in patients who had an inadequate response or intolerance to nonsteroidal antiinflammatory drug therapy. Overall, across these indications, adalimumab demonstrated a rapid onset of action, sustained efficacy with long-term treatment, and was well-tolerated, with few patients discontinuing treatment because of adverse events. The safety profile was similar to other TNF antagonists. Inhibition of TNF activity by adalimumab also significantly improved physical functioning and quality of life measures.
18752933 Anti-cyclic citrullinated peptide antibodies and IL-23p19 in psoriatic arthritis. 2009 Jan BACKGROUND: Anti-cyclic citrullinated peptide antibodies (anti-CCP) are reported to be found in 5-13% of patients with psoriatic arthritis (PsA). However, whether anti-CCP-positive PsA patients and rheumatoid arthritis (RA) patients have a similar pathophysiological background still remains uncertain. OBJECTIVE: To determine the prevalence of anti-CCP antibodies in patients with PsA and characterize these anti-CCP-positive patients of PsA. METHODS: We measured the serum levels of the anti-CCP antibodies in patients with PsA (n=16), psoriasis (n=15), RA (n=9) and healthy controls (n=11). Serum levels of rheumatoid factor (RF), matrix metalloproteinase-3 (MMP-3), cartilage oligomeric matrix protein (COMP), interleukin (IL)-23p19 and IL-12p40 were also measured in all the samples. RESULTS: Two of the 16 PsA patients (13%) were positive for anti-CCP antibodies with high titers of RF. However, the serum IL-23p19 levels were two orders of magnitude higher in the anti-CCP-positive PsA patients as compared with those in the RA patients and anti-CCP-negative PsA patients. No significant elevation of the serum levels of MMP-3, COMP and IL-12p40 was found in these patients. CONCLUSION: Thirteen percent of the PsA patients were positive for anti-CCP. These patients do not fulfill the American College of Rheumatology (ACR) classification criteria for RA so far. Furthermore, they showed the typical clinical features of PsA rather than those of RA. Although anti-CCP-positive PsA patients may possibly be have a risk of developing RA, we propose that these patients be classified, for the moment, into a independent subtype of PsA, as a different entity from RA.
17901669 Clinical and ultrasound assessment of the knee in children with juvenile rheumatoid arthri 2007 Sep OBJECTIVE: To correlate clinical features with ultrasound (USG) findings in the detection, quantification and follow up of inflammatory signs of knee in children with mono or pauciarticular juvenile rheumatoid arthritis (JRA). METHODS: Thirty patients (11 girls, 19 boys) with pauciarticular JRA (14 with monoarticular and 16 with bilateral knee involvement) were studied. Mean disease duration was 10 months (range 2 months to 5 yr). All knees were classified into two groups, according to the presence or absence of acute inflammation. Clinical assessment and ultrasound was done in all patients on the same day. All the patients received naproxen (15-20 mg/Kg/day) for a period of six months, after which clinical assessment and ultrasound study was repeated. RESULTS: Synovial proliferation and effusion, was demonstrated in a much higher frequency in those clinically active (Group A) as compared to these in clinical remission (Group B). Statistically significant differences between clinical and USG indices were seen. CONCLUSION: USG of knee is more sensitive than clinical assessment in detection of synovial effusion and thickening and plays a useful role in monitoring evolution of the inflammatory process, its quantification and for follow up.
16883927 Chronic musculoskeletal pain in children: part II. Rheumatic causes. 2006 Jul 15 Primary care physicians should have a working knowledge of rheumatic diseases of childhood that manifest primarily as musculoskeletal pain. Children with juvenile rheumatoid arthritis can present with painless joint inflammation and may have normal results on rheumatologic tests. Significant morbidity may result from associated painless uveitis, and children with juvenile rheumatoid arthritis should be screened by an ophthalmologist. The spondyloarthropathies (including juvenile ankylosing spondylitis and reactive arthritis) often cause enthesitis, and patients typically have positive results on a human leukocyte antigen B27 test and negative results on an antinuclear antibody test. Patients with acute rheumatic fever present with migratory arthritis two to three weeks after having untreated group A beta-hemolytic streptococcal pharyngitis. Henoch-Schbnlein purpura may manifest as arthritis before the classic purpuric rash appears. Systemic lupus erythematosus is rare in childhood but may cause significant morbidity and mortality if not treated early. Nonsteroidal anti-inflammatory drugs and physical therapy may be useful early interventions if a rheumatic illness is suspected. Family physicians should refer children when the diagnosis is in question or subspecialty treatment is required. Part I of this series discusses an approach to diagnosis with judicious use of laboratory and radiologic testing.
17672077 [Nosological diagnosis and outcomes of arthritis associated with streptococcal infection]. 2007 AIM: To specify the course and outcomes of arthritides associated with streptococcal infection (AASI). MATERIAL AND METHODS: The trial comprised 60 patients with arthritis (mean age 26.8 +/- 14.0). The patients met the following criteria: arthritis, elevated (< 500 U) titers of antistreptolisin-0 in the absence of heart disorders detected at Doppler-echocardiography (2D-echoCG), urogenital infection, Yersinia infection, psoriasis. In addition to routine clinical tests, the following investigations were made: tests for alloantigen of B-lymphocytes D8/17 and antigen HLA-B27, antibodies to polysaccharide of streptococcus of group A, bacteriological test of laryngeal smears for streptococcal infection, prospective follow-up (mean 31.2 +/- 19.6 mon) with 2D-echoCG. RESULTS: Rheumatic arthritis was rejected in 33.3% patients. Other diseases were diagnosed: early rheumatoid arthritis (10%), seronegative spondylarthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus, Still's disease, Konig's disease, sarcoidosis, gout, arthritis on the background of streptococcal nodular erythema. Acute rheumatoid fever (ARF) was diagnosed in 56.7% patients, poststreptococcal arthritis (PSA) in 10%. PSA differed from ARF by onset at the age of 36.0 +/- 10.2 years, short latent period (11.2 +/- 1.3 days), a significantly longer course of arthritis (95.0 +/- 3.9 days), recurrences. Alloantigen of B-lymphocytes was detected in 52.8% AASI patients (the difference from the control is highly significant (p < 0.001). Arthritis development was not associated with carriage of HLA-B27 carriage. CONCLUSION: In examination of AASI patients for diagnosis of ARV and PSA it is necessary to reject other diseases among which early RA (10%) is most frequent. It is recommended to make diagnosis of ARF in AASI patients with definition of risk factors (age 7-15 years, family history of rheumatic fever, carriage of alloantigen d8/17), 2.5-year and longer follow-up with 2D-echoCG. Diagnosis of PSA is made in rejection of ARF and in the presence of the following characteristics: development of the disease at the age 30-40 years, a short latent period of the infection, long-term persistent course of arthritis, insufficient effect of nonsteroid anti-inflammatory drugs, frequent affection of sacroiliac joints, recurrence, entezopathy.
16396980 EULAR recommendations for the management of early arthritis: report of a task force of the 2007 Jan OBJECTIVE: To formulate EULAR recommendations for the management of early arthritis. METHODS: In accordance with EULAR's "standardised operating procedures", the task force pursued an evidence based approach and an approach based on expert opinion. A steering group comprised of 14 rheumatologists representing 10 European countries. The group defined the focus of the process, the target population, and formulated an operational definition of "management". Each participant was invited to propose issues of interest regarding the management of early arthritis or early rheumatoid arthritis. Fifteen issues for further research were selected by use of a modified Delphi technique. A systematic literature search was carried out. Evidence was categorised according to usual guidelines. A set of draft recommendations was proposed on the basis of the research questions and the results of the literature search.. The strength of the recommendations was based on the category of evidence and expert opinion. RESULTS: 15 research questions, covering the entire spectrum of "management of early arthritis", were formulated for further research; and 284 studies were identified and evaluated. Twelve recommendations for the management of early arthritis were selected and presented with short sentences. The selected statements included recognition of arthritis, referral, diagnosis, prognosis, classification, and treatment of early arthritis (information, education, non-pharmacological interventions, pharmacological treatments, and monitoring of the disease process). On the basis of expert opinion, 11 items were identified as being important for future research. CONCLUSIONS: 12 key recommendations for the management of early arthritis or early rheumatoid arthritis were developed, based on evidence in the literature and expert consensus.
18473978 Use of etanercept in the treatment of psoriasis and psoriatic arthritis. 2006 Sep Psoriasis and psoriatic arthritis are debilitating inflammatory immunemediated diseases which are chronic in nature and often require lifelong attention. Traditional therapies used to combat these diseases lack sufficient long-term efficacy and are associated with a number of toxicities. Failing to adequately satisfy both patients and physicians, traditional therapies have proven insufficient and have left few options. Etanercept is a tumor necrosis factor (TNF) antagonist that reduces elevated TNF levels by competitively binding to both TNF-alpha and TNF-beta and inhibiting the proinflammatory cascade. Providing a valuable treatment option alone, etanercept can also be effectively administered in conjunction with traditional treatments. Etanercept is self administered by subcutaneous (SC) injection, making treatment less of a burden for patients by eliminating the need for frequent office visits and laboratory testing. Etanercept is approved in the US for the treatment of psoriasis, psoriatic arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, and ankylosing spondylitis.
16846531 Coexpression and interaction of CXCL10 and CD26 in mesenchymal cells by synergising inflam 2006 Leukocyte infiltration during acute and chronic inflammation is regulated by exogenous and endogenous factors, including cytokines, chemokines and proteases. Stimulation of fibroblasts and human microvascular endothelial cells with the inflammatory cytokines interleukin-1beta (IL-1beta) or tumour necrosis factor alpha (TNF-alpha) combined with either interferon-alpha (IFN-alpha), IFN-beta or IFN-gamma resulted in a synergistic induction of the CXC chemokine CXCL10, but not of the neutrophil chemoattractant CXCL8. In contrast, simultaneous stimulation with different IFN types did not result in a synergistic CXCL10 protein induction. Purification of natural CXCL10 from the conditioned medium of fibroblasts led to the isolation of CD26/dipeptidyl peptidase IV-processed CXCL10 missing two NH2-terminal residues. In contrast to intact CXCL10, NH2-terminally truncated CXCL10(3-77) did not induce extracellular signal-regulated kinase 1/2 or Akt/protein kinase B phosphorylation in CXC chemokine receptor 3-transfected cells. Together with the expression of CXCL10, the expression of membrane-bound CD26/dipeptidyl peptidase IV was also upregulated in fibroblasts by IFN-gamma, by IFN-gamma plus IL-1beta or by IFN-gamma plus TNF-alpha. This provides a negative feedback for CXCL10-dependent chemotaxis of activated T cells and natural killer cells. Since TNF-alpha and IL-1beta are implicated in arthritis, synovial concentrations of CXCL8 and CXCL10 were compared in patients suffering from crystal arthritis, ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis. All three groups of autoimmune arthritis patients (ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis) had significantly increased synovial CXCL10 levels compared with crystal arthritis patients. In contrast, compared with crystal arthritis, only rheumatoid arthritis patients, and not ankylosing spondylitis or psoriatic arthritis patients, had significantly higher synovial CXCL8 concentrations. Synovial concentrations of the neutrophil chemoattractant CXCL8 may therefore be useful to discriminate between autoimmune arthritis types.
19227718 Jaccoud's arthropathy revisited. 2008 Jul Jaccoud's arthropathy is a chronic, non erosive, rheumatoid-like deformity of the hands associated with rheumatic fever and systemic lupus erythematosus (SLE). This deforming arthropathy may present difficulties in differentiating SLE from rheumatoid arthritis (RA). We present a case of a 43-year-old woman who was initially diagnosed with Sjogren's syndrome and rheumatoid arthritis (RA), and several years later, with SLE. The diagnosis of RA was based mainly on the presence of hands deformities. On evaluation she had reducible hands deformities and had no radiographic evidence of joint destruction; thus joint deformities were not consistent with RA but to Jaccoud's arthropathy associated with SLE. Here, we revisit Jaccoud's arthropathy and highlight the importance of a careful joint examination in the assessment of rheumatic diseases.
18360594 Rituximab and its potential for the treatment of rheumatoid arthritis. 2006 Jun Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder which causes deforming joint disease and a spectrum of extraarticular manifestations. Poor disease control may lead to functional impairment and loss of independence. In recent times a prominent role for B cells in the pathogenesis of RA has been suggested. Two major theories have been postulated to explain the role of rheumatoid factor (RF) in the RA inflammatory process and the reason for RF overproduction; the loss of tolerance model and the autonomous mutated B cell model. With this in mind, strategies have been adopted to deplete B cells including the use of the anti-CD20 antibody rituximab. Rituximab leads to complement mediated lysis of B cells as well as antibody-dependant cellular cytotoxicity. It has been hypothesized that rituximab may also initiate apoptosis in RA and alter the ability of B cells to respond to antigen and other stimuli. Several recent studies using rituximab have demonstrated significant declines in RA activity providing evidence for the role of B cells in RA. Rituximab would appear to be a major addition to the increasing therapeutic options for sufferers of RA.
16450148 [Imaging methods in rheumatology: imaging in psoriasis arthritis (PsA)]. 2006 Mar Conventional radiography is still the standard method of imaging in PsA since it displays many joints at the same time, thereby allowing different types of joint involvement to be recognized. Moreover, thanks to the high resolution of radiography, bony changes in a single joint are depicted in a brilliant way. Several features of psoriatic arthritis allow the distinction from rheumatoid arthritis, including the frequent involvement of the distal interphalangeal joints, asymmetry of joint involvement, axial involvement of finger joints, oligoarticular involvement; however, symmetric polyarthritis is also possible. At the level of the single joint, there are signs of severe destructive changes potentially leading to mutilation and at the same time signs of periostal bone proliferation and ankylosis may be present. Bony proliferation and/or osteolysis are not restricted to the joint region but can affect also the total phalanx with bone apposition or concentric osteolysis which may lead to a complete disappearance of phalanxes. For purposes of quantification of radiographic changes scoring methods are used that were originally developed for rheumatoid arthritis. So far, there is only one validated scoring method that was specifically designed for PsA and that takes into account both features of PsA, damage as well as proliferation of bone. In contrast to conventional radiography, MRI and sonography are able to visualize inflammatory processes within the soft tissue (joint capsules, tendon sheaths, tendon insertions, etc.), allowing an estimation of disease activity. Scintigraphy is nonspecific and can only be used to detect clinically silent inflammatory spots. The relatively frequent spinal (axial) involvement is similar to that seen in ankylosing spondylitis. However, unilateral sacroiliitis, asymmetry of syndesmophytes and development of parsyndesmophytes may distinguish PsA from ankylosing spondylitis. While conventional radiography demonstrates the bony consequences of inflammation in the spine, MRI also shows the active inflammatory changes in sacroiliacal joints and vertebrae.
17102943 Frequency of rheumatic diseases in patients with autoimmune thyroid disease. 2007 Apr We aimed to investigate the frequency of rheumatic diseases in patients suffering from autoimmune thyroid diseases (ATD). Sixty-five patients (56 F, 9 M), who were followed by diagnosis of ATD, were questioned and examined for the presence of rheumatic disease. Basic laboratory tests and antithyroid antibodies, antinuclear antibody and rheumatoid factor (RF) levels were also measured by appropriate methods. Various rheumatic diseases were detected in 40 (62%) of patients with ATD. The most frequent rheumatic conditions were fibromyalgia, recurrent aphthous stomatitis, osteoarthritis, keratoconjunctivitis sicca and xerostomia and carpal tunnel syndrome which were detected in 20 (31%), 13 (20%), 10 (15%), 9 (14%) and 8 (12%) of patients, respectively. Autoimmune diseases, except Sjogren's syndrome, which were detected in ten patients with ATD, are as follows-vitiligo: two; autoimmune hepatitis: two; oral lichen planus: one, ulcerative colitis: one, inflammatory arthritis in four patients (two of them had rheumatoid arthritis, one had psoriasis and psoriatic arthritis and one had mixed collagen tissue disease). RF was positive in two patients, one of them had rheumatoid arthritis and FANA was positive in six (9%) patients; all of them had hypothyroidism. The frequency of rheumatic diseases seems to be higher in patients suffering from ATD. Initial evaluation and a regular checking for rheumatic diseases in patients suffering from ATD were recommended.
16303821 Serum lipid levels in Sjögren's syndrome. 2006 Apr OBJECTIVES: Altered lipid levels may occur in autoimmune diseases, for example low cholesterol levels have been described in rheumatoid arthritis (RA). Serum lipid profiles in patients with Sjögren's syndrome (SS) have not been investigated. We hypothesized decreased lipid levels in SS patients and an inverse relationship with disease activity. METHODS: Serum lipid levels [total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides] and additional data regarding disease measures (clinical immunology parameters, focus score from labial salivary gland biopsy, salivary flow and ophthalmological measures) were available for 46 primary SS patients and 12 xerostomic controls. RESULTS: Significant differences between SS patients and controls means (s.d.) were seen for HDL (P = 0.04) and total cholesterol (P = 0.02). LDL (P = 0.12) and triglyceride (P = 0.08) levels were not different. In SS patients, but not in controls, total cholesterol (P = 0.003) and HDL cholesterol (P = 0.003) predicted immunoglobulin G levels. Anti-SSA antibodies were related to a lower total cholesterol (P = 0.02) and anti-SSB antibodies to a lower HDL cholesterol level (P = 0.0497). CONCLUSIONS: Significant differences were seen in serum lipid levels of primary SS patients and these were associated with serological measures of inflammation. Our results are comparable to earlier findings in RA patients and raise questions related to adverse cardiovascular consequences in SS.
17641008 Lack of reactive oxygen species breaks T cell tolerance to collagen type II and allows dev 2007 Aug 1 The view on reactive oxygen species (ROS) in inflammation is currently shifting from being considered damaging toward having a more complex role in regulating inflammatory reactions. We recently demonstrated a role of ROS in regulation of animal models for the autoimmune disease rheumatoid arthritis. Low levels of ROS production, due to a mutation in the Ncf1 gene coding for the Ncf1 (alias p47(phox)) subunit of the NADPH oxidase complex, was shown to be associated with increased autoimmunity and arthritis severity in both rats and mice. To further investigate the role of ROS in autoimmunity, we studied transgenic mice expressing collagen type II (CII) with a mutation (D266E) in the immunodominant epitope that mimics the rat and human CII (i.e., mutated mouse collagen or MMC). This mutation results in a stronger binding of the epitope to the MHC class II molecule and leads to more pronounced tolerance and resistance to arthritis induced with rat CII. When the Ncf1 mutation was bred into these mice, tolerance was broken, resulting in enhanced T cell autoreactivity, high titers of anti-CII Abs, and development of severe arthritis. These findings highlight the importance of a sufficient ROS production in maintenance of tolerance to self-Ags, a central mechanism in autoimmune diseases such as rheumatoid arthritis. This is important as we, for the first time, can follow the effect of ROS on molecular mechanisms where T cells are responsible for either protection or promotion of arthritis depending on the level of oxygen species produced.
16598488 [The TNK ankle: short- and mid-term results]. 2006 May Total ankle replacement has been introduced in the last 30 years. The TNK ankle is build from ceramics, and it was continuously improved. This prosthesis has the longest fellow-up times. Seventy ankle prostheses of the newest generation has been implanted between 1991 and 2001. Of these, 67 prostheses were assessed clinically and radiographically after 62 months (range, 24 to 132 months). Three ankles have been revised. The clinical score improved for the patients with primary or posttraumatic arthritis from 34 to 86, and for the patients with rheumatoid arthritis from 45 to 74. Loosening was found in 4 ankles with non-rheumatoid arthritis, and in 17 ankles with rheumatoid ankles. Total ankle replacement has emerged to a valuable alternative to ankle arthrodesis, and satisfactory results have been achieved with the current implants. The bone-implant interphase might play a most important factor for success. There is evidence that the biologic advantages of ceramics may help to improve long-lasting success in total ankle replacement.
18466577 Adjusting for sex and anti-CCP levels in linkage analysis of rheumatoid arthritis. 2007 We incorporate population effects of sex and antibodies directed against cyclic citrullinated peptides (anti-CCP) into the linkage analysis of rheumatoid arthritis (RA) with microsatellites data provided by the North American Rheumatoid Arthritis Consortium in Genetic Analysis Workshop 15.The method stems from a generalized linear mixed model that incorporates the marginal population effects of important covariates. The resulting test for linkage is based on a score test in a pseudo-likelihood of this model. The mathematical derivation is given elsewhere but the test has a simple and appealing form: it assigns weights to excess identity-by-descent sharing between pairs of related individuals depending on the individual-specific values of the covariates and phenotypes.Although RA is three times more prevalent in women than in men, the weights derived for male-male, female-male, and female-female affected sib pairs turn out to be very similar and the sex-adjusted analysis hardly differs from an unadjusted analysis. High anti-CCP levels are known to strongly predict RA. Our test assigns very small weights to pairs whose anti-CCP levels are high for the two siblings, sib pairs with two low anti-CCP levels are those most contributing to the evidence for linkage. Comparison of the unadjusted and the anti-CCP-adjusted analyses identifies persisting peaks mapping to regions that can be attributed to a 'dimension' of RA independent of anti-CCP.