Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
18825755 Collagen type II is recognized by a pathogenic antibody through germline encoded structure 2008 Oct Collagen type II (CII) is a cartilage-specific target of pathologic humoral autoimmune responses in rheumatoid arthritis as well as in the collagen-induced arthritis model. The aim of the present study is to investigate the critical amino acid residues conferring CII epitope specificity of the prototypic arthritogenic murine mAb CIIC1. A homology model of the CIIC1 single-chain antibody fragment (CIIC1scFv) in complex with its triple helical epitope was established. In silico predictions based on extensive molecular dynamics simulations were experimentally tested by the recombinant expression and functional analysis of CIIC1scFv containing alanine replacements allowing the identification of crucial CII-binding sites in the CDR2 and CDR3 regions of both heavy and light chains. Since the conversion of the CIIC1scFv sequence into the respective germline at all 13 somatically mutated positions did not affect its CII binding, our data indicate that potentially harmful cartilage-specific humoral autoimmunity could be germline encoded. The molecular modeling further demonstrates that the rigid collagen triple helix restricts the likelihood of molecular interactions with the CDR regions of the antibody considerably compared with globular antigens. These sterical constraints provide an explanation as to why somatic mutations in the arthritogenic autoantibody have no obvious impact on CII recognition.
18342464 Stir-baked Fructus gardeniae (L.) extracts inhibit matrix metalloproteinases and alter cel 2008 May 8 Matrix metalloproteinases (MMPs) play vital roles in many pathological conditions, including cancer, cardiovascular disease, arthritis and inflammation. Modulating MMP activity may therefore be a useful therapeutic approach in treating these diseases. Qing-Kai-Ling is a popular Chinese anti-inflammatory formulation used to treat symptoms such as rheumatoid arthritis, acute hypertensive cerebral hemorrhage, hepatitis and upper respiratory tract infection. In this paper, we report that one of the components of Qing-Kai-Ling, Fructus gardeniae, strongly inhibits MMP activity. The IC50 values for the primary herbal extract and water extract against MMP-16 were 32 and 27 microg/ml, respectively. In addition, we show that the herbal extracts influence HT1080 human fibrosarcoma cell growth and morphology. These data may provide molecular mechanisms for the therapeutic effects of Qing-Kai-Ling and herbal medicinal Fructus gardeniae.
18163522 Risks and relative risks of Wegener's granulomatosis among close relatives of patients wit 2008 Jan OBJECTIVE: The etiology of Wegener's granulomatosis (WG) supposedly involves interplay between genetic susceptibility and environmental triggers. However, little is known about whether WG actually clusters in families. Information on the degree of familial aggregation in WG is of clinical relevance, because patients with WG often want to know whether their diagnosis puts their closest relatives at increased risk of the disease. The aim of this study was to investigate the risk of WG in relatives of patients with WG. METHODS: Using Swedish nationwide registers on morbidity, family structure, and vital status, we compared the occurrence of WG (register-based plus chart review) among 6,670 first-degree relatives and 428 spouses of 1,944 Swedish patients with WG with the occurrence among 68,994 first-degree relatives and 4,812 spouses of 19,655 control subjects from the general population. Relative risks were estimated using the Cox proportional hazards regression model. RESULTS: Two of the 6,670 first-degree relatives of patients with WG and 13 of the 68,994 first-degree relatives of their population controls had WG, resulting in a relative risk of 1.56 (95% confidence interval 0.35-6.90). None of the 428 spouses of patients had WG. CONCLUSION: In absolute terms, the occurrence of WG among close biologic and nonbiologic relatives of patients with WG is low. In terms of relative risk, our results provide strong evidence against a pronounced increase in familial risk such as that noted for systemic lupus erythematosus, irritable bowel disease, and multiple sclerosis but are compatible with familial aggregation of a magnitude similar to that for rheumatoid arthritis.
17709958 Bidirectional communication between the brain and the immune system: implications for phys 2006 This review describes mechanisms of immune-to-brain and brain-to-immune signaling involved in mediating physiological sleep and altered sleep with disease. The central nervous system (CNS) modulates immune function by signaling target cells of the immune system through autonomic and neuroendocrine pathways. Neurotransmitters and hormones produced and released by these pathways interact with immune cells to alter immune functions, including cytokine production. Cytokines produced by cells of the immune and nervous systems regulate sleep. Cytokines released by immune cells, particularly interleukin-1beta and tumor necrosis factor-alpha, signal neuroendocrine, autonomic, limbic and cortical areas of the CNS to affect neural activity and modify behaviors (including sleep), hormone release and autonomic function. In this manner, immune cells function as a sense organ, informing the CNS of peripheral events related to infection and injury. Equally important, homeostatic mechanisms, involving all levels of the neuroaxis, are needed, not only to turn off the immune response after a pathogen is cleared or tissue repair is completed, but also to restore and regulate natural diurnal fluctuations in cytokine production and sleep. The immune system's ability to affect behavior has important implications for understanding normal and pathological sleep. Sleep disorders are commonly associated with chronic inflammatory diseases and chronic age- or stress-related disorders. The best studied are rheumatoid arthritis, fibromyalgia and chronic fatigue syndromes. This article reviews our current understanding of neuroimmune interactions in normal sleep and sleep deprivation, and the influence of these interactions on selected disorders characterized by pathological sleep.
17599768 Autoimmune diseases in a Danish cohort of 4,866 carriers of constitutional structural chro 2007 Jul OBJECTIVE: Constitutional structural chromosomal rearrangements (CSCRs) have facilitated the identification of genes associated with early-onset monogenic disorders and, more recently, genes associated with common and late-onset disorders. In an attempt to find genetic clues to their etiologies, we studied the risk of autoimmune diseases in a Danish cohort of CSCR carriers. METHODS: We followed up 4,866 CSCR carriers over 71,230 person-years (1980 through 2004) for autoimmune diseases recorded in the Danish Hospital Discharge Register. Standardized incidence ratios (SIRs) and 95% confidence intervals (95% CIs) served as measures of the relative risk. To identify possible candidate loci for autoimmune diseases, the reported chromosomal breakpoints and deletions in CSCR carriers who developed autoimmune diseases were compared with previously suggested loci for these diseases. RESULTS: The overall risk of any autoimmune disease among CSCR carriers was inconspicuous (SIR 1.2 [95% CI 0.95-1.5]; n = 74 cases observed versus 61.3 expected), but carriers of rearrangements involving chromosomes 2, 19, and 21 were at significantly increased risk. For the specific autoimmune diseases studied, cohort members were at significantly increased risk of Dupuytren's contracture, pernicious anemia, and juvenile rheumatoid arthritis (JRA). Sixteen carriers who developed an autoimmune disease had a chromosomal breakpoint or deletion coinciding with a previously suggested locus, including deletions 18p11, 18q22, and 22q11 associated with JRA. CONCLUSION: CSCR carriers do not have a generalized predisposition to autoimmune diseases. However, we confirmed a number of reported susceptibility loci for JRA, and we suggest new susceptibility loci on chromosomes 5 and 11 for Dupuytren's contracture, and 19p13 as a possible shared susceptibility locus for a range of autoimmune diseases.
17042020 Rheumatology nurse practitioners' perceptions of their role. 2006 Jun OBJECTIVES: To identify the current practices of rheumatology nurse practitioners and ascertain their perceptions of how their role could be enhanced. METHOD: A cross-sectional questionnaire study of currently employed nurse practitioners in rheumatology in the United Kingdom (UK) was undertaken. RESULTS: 200 questionnaires were distributed and 118 nurses responded. Ninety-five respondents met the inclusion criteria for undertaking an advanced nursing role. Typical conditions dealt with included: rheumatoid arthritis (96.8%); psoriatic arthritis (95.8%); osteoarthritis (63.2%); ankylosing spondylitis (62.8%); systemic lupus erythematosus (51.6%); and scleroderma (34.7%). Drug monitoring, education, counselling of patients and arranging basic investigations were routinely performed by more than 80% of respondents. A smaller proportion performed an extended role that included dealing with referrals, research and audit, the administration of intra-articular injections, and admission of patients. Specific attributes identified as being necessary for competence were: knowledge and understanding of rheumatic diseases (48.4%); drug therapy (33.7%); good communication skills (35.8%); understanding of the roles of the team (27.4%); working effectively (23.2%) as part of a multidisciplinary team; assessment of patients by physical examination (28.4%); teaching (26.3%), research (17.9%); organizational skills (14.7%); and the interpretation of investigations (9.5%). Factors that could enhance their role included: attendance at postgraduate courses (30.5%); obtaining further qualifications (13.7%); active participation in the delivery of medical education (41.1%); training in practical procedures (31.6%); protected time and resources for audit and research (11.6%); formal training in counselling (11.6%); and implementation of nurse prescribing (10.5%). CONCLUSION: Nurse practitioners already have a wide remit and play an invaluable part in the delivery of modern rheumatology services. An extended role could improve patient care and enhance nursing career pathways in rheumatology.
16863900 Fever of unknown origin due to preleukemia/myelodysplastic syndrome: the diagnostic import 2006 Jul Fever of unknown origin (FUO) is a common clinical diagnostic dilemma. In the elderly, causes of FUO most commonly include malignancy or infection, and less commonly include collagen vascular diseases. Among the collagen vascular diseases causing FUO in the elderly, polymyalgia rheumatica/temporal arteritis, and adult Still's disease (adult juvenile rheumatoid arthritis) are difficult diagnoses to prove. Among the infectious causes of FUO in the elderly are subacute bacterial endocarditis, intra-abdominal abscesses, and extrapulmonary tuberculosis. In the elderly, neoplastic causes of FUO include lymphomas, hepatomas, renal cell carcinomas, and hepatic or central nervous system metastases. Acute leukemias, particularly during "blast" transformation, may present as acute fevers in the absence of infection, but are rare causes of FUO. Preleukemia/myelodysplastic syndromes are exceedingly rare causes of FUO. We present a case of an elderly man who presented with findings that initially suggested adult Still's disease. Prolonged and profound monocytosis provided the key clue to his subsequent diagnosis of preleukemia/myelodysplastic syndrome. In this patient, a positive Naprosyn test result also suggested a neoplastic cause for his FUO. After months of prolonged fevers, myelocytes/metamyelocytes were eventually demonstrated in his peripheral smear during hospital evaluation. These findings, in concert with the persistent monocytosis, highly elevated ferritin levels, polyclonal gammopathy on serum protein electrophoresis, and eventual presence of myelocytes/metamyelocytes on peripheral smear, prompted a bone marrow test that demonstrated blast cells confirming the diagnosis of preleukemia myelodysplastic syndrome as the cause of this patient's FUO.
16542479 The p38 mitogen-activated protein kinase signaling cascade in CD4 T cells. 2006 Since the identification of the p38 mitogen-activated protein kinase (MAPK) as a key signal-transducing molecule in the expression of the proinflammatory cytokine tumor necrosis factor (TNF) more than 10 years ago, huge efforts have been made to develop inhibitors of p38 MAPK with the intent to modulate unwanted TNF activity in diseases such as autoimmune diseases or sepsis. However, despite some anti-inflammatory effects in animal models, no p38 MAPK inhibitor has yet demonstrated clinical efficacy in human autoimmune disorders. One possible reason for this paradox might relate to the fact that the p38 MAPK signaling cascade is involved in the functional regulation of several different cell types that all contribute to the complex pathogenesis of human autoimmune diseases. In particular, p38 MAPK has a multifaceted role in CD4 T cells that have been implicated in initiating and driving sustained inflammation in autoimmune diseases, such as rheumatoid arthritis or systemic vasculitis. Here we review recent advances in the understanding of the role of the p38 MAPK signaling cascade in CD4 T cells and the consequences that its inhibition provokes in T cell functions in vitro and in vivo. These new data suggest that p38 MAPK inhibitors may elicit several unwanted effects in human autoimmune diseases but may be useful for the treatment of allergic disorders.
18349863 A paraneoplastic case of palmar fasciitis and polyarthritis syndrome. 2008 May BACKGROUND: A 58-year-old woman presented with arthritis of the small joints of her hands and rapidly progressive joint contractures. She was wheelchair bound within 2 months of the onset of her symptoms. Physical examination revealed synovitis of the small joints of her hands and palmar fasciitis. The patient had been diagnosed with pancreatic carcinoma approximately 1 year before the presentation of her rheumatic symptoms, and had undergone radical pancreatico-duodenectomy. INVESTIGATIONS: Physical examination; routine laboratory work, including full blood count and measurement of erythrocyte sedimentation rate and C-reactive protein; serological tests for rheumatoid factor, antinuclear antibodies and extractable nuclear antibodies; measurement of serum tumor markers; radiological investigations, including X-rays of her hands and feet, whole-body CT-scans and radioisotope bone scan. DIAGNOSIS: The patient's rheumatic presentation was diagnosed as a paraneoplastic syndrome associated with pancreatic carcinoma. MANAGEMENT: The patient's condition was managed with corticosteroids and methotrexate. No residual tumor or evidence of metastatic disease have been detected in the 1.5 years since the initial presentation of her rheumatic symptoms.
18311807 Spondylarthritis in the absence of B lymphocytes. 2008 Mar The highly effective treatment of rheumatoid arthritis by B cell depletion and the presence of B cells in the peripheral and axial lesions of patients with spondylarthritis (SpA) raise the question as to whether B lymphocytes could also be an appropriate therapeutic target in the latter disease. We describe 2 male HLA-B27-positive patients who had active SpA despite absence of B cells. One patient developed SpA with sacroiliitis and asymmetric oligoarthritis after having been diagnosed as having severe Bruton agammaglobulinemia. Since extensive investigations excluded an infectious origin of the SpA, this case illustrates that functional B cells and/or gamma globulins are not strictly required for SpA pathogenesis. The second patient had severe axial and peripheral SpA that was treated successfully with etanercept. After discontinuation of etanercept treatment because of non-Hodgkin's B cell lymphoma, both axial and peripheral SpA symptoms relapsed rapidly, and this exacerbation of articular disease activity was not modulated by successful B cell depletion therapy for the lymphoma. Although case reports have obvious limitations, our clinical observations provide evidence that active SpA can occur in the absence of functional mature B cells and thus emphasize the need for systematic studies of the exact role and function of B lymphocytes in this disease.
18176867 Anti-polymer antibodies are correlated with pain and fatigue severity in patients with fib 2008 Feb OBJECTIVE: To investigate the prevalence of antipolymer antibody (APA) in patients with fibromyalgia (FM) and to examine its association with FM severity symptoms. METHODS: The study population consisted of 79 FM patients and 75 controls: 32 with psoriatic arthritis and 43 with rheumatoid arthritis APA levels were indirectly assayed using a commercial ELISA kit from Corgenix (Westmister, Colorado, USA). Optical density (OD) values were recorded on duplicates of each of the reference and patient samples. Among clinical variables we investigated pain, measured according to visual analog scales (VAS: 0-100), fatigue, stiffness, anxiety, depression, all measured by VAS (0-100), and health status measured by Fibromyalgia Impact Questionnaire (FIQ). RESULTS: Sixteen of the 79 FM patients (20.3%) and 12/78 controls (15.4%) were positive for APAs (P = 0.536). Following ROC analysis, area under curve (AUC) was 0.49 (95% CI: 0.40, 0.58). Focusing on FM patients, we observed a correlation between APA titre and pain (tau: - 0.221; P = 0.020) and fatigue (tau: - 0.205; P = 0.032) at univariate analysis. Binomial regression analysis, controlling for clinical and demographic variables, showed that pain (PPR: 0.923; P = 0.007) and fatigue (PPR: 0.948; P = 0.024) were significantly associated with APA test sensitivity. CONCLUSIONS: APA test exhibited a low sensitivity in FM patients and it did not distinguish this group of patients from the controls enrolled in this study. Interestingly, positive APA test prevalence increased with less severe pain or fatigue.
18172922 Diagnostic sensitivity and specificity of Doppler ultrasound in rheumatoid arthritis. 2008 Jan OBJECTIVE: To evaluate the sensitivity and specificity of Doppler ultrasound (DUS) in diagnosing arthritis in the wrist and hands, and, if possible, to define a cutoff level for our ultrasound measures for inflammation, resistive index (RI), and color fraction. METHODS: Using DUS, 88 patients with active RA were selected for study and 27 healthy controls. A total of 419 joints were examined. The synovial vascularization was determined by color Doppler and spectral Doppler estimating the color fraction (the percentage of color pixels inside the synovium was the region of interest) and RI in wrist, metacarpophalangeal (MCP), and proximal interphalangeal (PIP) joints. Receiver-operator characteristic (ROC) curves were made for both US measures. Cutoff levels were selected from the ROC curves as the values with the optimum sensitivity and specificity. RESULTS: Analyses were carried out for small joints (MCP and PIP), wrists, and for all joints (pooled). Pooled joint analysis showed the area under the curve for both RI and color fraction was 0.84. The cutoff level for the color fraction was 0.01 and for RI 0.83. With these cutoff levels, the sensitivity and specificity for the color fraction were 0.92 and 0.73, respectively. For RI a sensitivity of 0.72 and specificity of 0.70 were found. Analysis of small joints and wrist gave very similar results. CONCLUSION: DUS may detect vascularization of the inflamed synovium with a high sensitivity and a moderate specificity with selected cutoff levels.
17611158 T cell immunomodulation--the Holy Grail of therapeutic tolerance. 2007 Aug The concept and practice of therapeutic tolerance has successfully been applied to animal models of autoimmunity and transplantation for more than 2 decades. Finally, there are encouraging signs of its translation to clinical practice. Short courses of anti-CD3 monoclonal antibody therapy have provided lasting benefits in recent-onset type 1 diabetes in association with evidence for the induction of immunoregulatory mechanisms. Co-stimulation blockade with abatacept (CTLA4-Ig) will soon be licensed for the treatment of rheumatoid arthritis - over the past year phase III studies have demonstrated impressive improvement in subjective and objective signs of the disease. T cell depletion is in development for several conditions, again with recent studies demonstrating evidence of immune regulation in some instances. More specific antigen-directed peptide therapies have also been applied to atopic asthma, type 1 diabetes, and adult and juvenile arthritis. The tragic sequelae of the phase I trial of TGN1412 at Northwick Park demonstrated the delicate, but unpredictable, therapeutic ratio of some T-cell-directed treatments and, in the UK, have led to new guidelines for early-phase clinical trials of immune-directed therapies.
17559763 Treatment of severe, painful pes planovalgus deformity with hindfoot arthrodesis and wedge 2007 May BACKGROUND: This study tested the hypothesis that modification of the standard technique of hindfoot arthrodesis with the use of a wedge-shaped tricortical allograft would improve the amount of correction of pes planovalgus deformity. The results were compared to previous reports. METHODS: Between 1998 and 2005, the senior author (LBC) performed 13 hindfoot arthrodeses on 12 patients using an allograft to improve correction of the deformity for severe, painful pes planovalgus deformity. The average patient age was 55 (range 27 to 77) years. There were seven women and five men. The indications were posterior tibial tendon dysfunction (seven feet), rheumatoid arthritis (three feet), post-traumatic arthritis and deformity (one foot), congenital pes planovalgus (one foot), and tarsal coalition (one foot). RESULTS: Twelve of 13 feet achieved union by 12 weeks postoperatively. There was one nonunion. The average time to fusion was 12 weeks. All 12 patients were satisfied with the results of the operation. The average postoperative American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot score was 87 points, and the AOFAS Midfoot score was 85 points. Preoperative and postoperative radiographs were compared to evaluate correction of deformity. On lateral weightbearing views, the talo-first metatarsal angle improved from 15 to 6 degrees, and the lateral talocalcaneal angle improved from 48 to 35 degrees. On anteroposterior views, the talo-first metatarsal angle improved from 17 to 7 degrees, the talonavicular coverage decreased from 28 to 13 degrees, and the talocalcaneal angle improved from 23 to 13 degrees. CONCLUSIONS: A simple modification of the addition of allograft to a common procedure of hindfoot arthrodesis to treat severe, painful pes planovalgus results is reliable and offers satisfactory correction.
17366006 The epidemiology of and risk factors for invasive Staphylococcus aureus infections in west 2007 We conducted a prospective study of all cases of invasive Staphylococcus aureus infections (ISA) in the catchment area of Skaraborg Hospital (population 255,109) in western Sweden from March 2003 to February 2005. The annual incidence was 33.9 cases/100,000 population. Of these, 49% were classified as community-acquired, 32% as nosocomial and 19% as health care-associated. The mean age was 65 y. We registered children (age < or = 18 y) in 13 episodes. The most common predisposing illnesses/conditions were persons undergoing haemodialysis (relative risk 291), peritoneal dialysis (relative risk 204), persons with rheumatoid arthritis (relative risk 9), diabetes mellitus (relative risk 8), and cancer (relative risk 7). The patients were treated at various departments; only 18% of the episodes were primarily cared for at a department of infectious diseases. The most common diagnosis was soft tissue infection (27% of the episodes), bacteraemia without focus (19%), arthritis (15%), and line-associated infection (14%). A total of 197 invasive isolates was obtained, the vast majority from blood, in 141 of 170 episodes. We documented the wide spectrum of signs and symptoms. One- quarter of the patients had no history of fever, and one-third of the bacteraemia patients had normal white blood cell count (<10 x 10(9)/l) at presentation. All cases were of MSSA (methicillin-sensitive Staphylococcus aureus).
17249854 A 'league table' of contingent valuation results for pharmaceutical interventions: a hard 2007 Pharmaceutical expenditure represents a large percentage of total healthcare expenditure, and has thus received much attention within the economic evaluation literature. However, although the number of contingent valuation (CV) studies measuring willingness to pay (WTP) in healthcare has increased, little is known about the relative magnitude of values elicited across different interventions, diseases or countries, or the methodological comparability of these values. We address this gap by seeking to establish if it is feasible to use elicited WTP values in resource allocation, illustrated by attempting to compile a 'league table' of WTP values for pharmaceutical interventions. A review database was compiled for CV studies in healthcare published from January 1985 to December 2005. Of 210 studies identified, 40 considered pharmaceutical interventions. Values are presented as mean or median WTP values, adjusted where necessary to pound and $US for 2004/5. Lack of reporting in some instances of either the mean or median, together with heterogenous methods and infrequent reporting of costs, made 'league table' construction difficult. This raises questions about the use of existing studies for resource allocation decisions, despite the fact that most studies were seemingly undertaken for policy objectives. However, four interventions had more than one study, making it possible to compare the values elicited. The values elicited across studies were fairly consistent for two interventions (anti-hypertensive therapy and tumour necrosis factor [TNF]-alpha blockade for rheumatoid arthritis), whereas WTP values for insulin and post-operative emesis therapy were very divergent. No single methodological difference seemed to explain this pattern; however, the more methodological differences between studies the greater the likelihood of divergent values. A checklist, or minimum reporting set of information, is the first step towards improving the consistency of methods, and therefore values, published. In the longer term, a move towards the use of a reference case akin to that used for cost-utility studies would seem important if such studies are to be used for comparative purposes and thereby be relevant to resource allocation decision making.
17021107 Design, construction, and evaluation of a specific chimeric antigen to diagnose chagasic i 2006 Oct Chagas' disease is routinely diagnosed by detecting specific antibodies (Abs) using serological methods. The methodology has the drawback of potential cross-reactions with Abs raised during other infectious and autoimmune diseases (AID). Fusion of DNA sequences encoding antigenic proteins is a versatile tool to engineer proteins to be used as sensitizing elements in serological tests. A synthetic gene encoding a chimeric protein containing the C-terminal region of C29 and the N-terminal region of TcP2beta was constructed. A 236-serum panel, composed of 104 reactive and 132 nonreactive sera to Chagas' disease, was used to evaluate the performance of the chimera. Among the nonreactive sera, 65 were from patients with AID (systemic lupus erythematosus and rheumatoid arthritis) or patients infected with Leishmania brasiliensis, Brucella abortus, Streptococcus pyogenes, or Toxoplasma gondii. The diagnostic performances of the complete TcP2beta (TcP2betaFL) and its N-terminal region (TcP2betaN) were evaluated. TcP2betaFL showed unspecific recognition toward leishmaniasis (40%) and AID Abs (58%), while TcP2betaN showed no unspecific recognition. The diagnostic utility of the chimera was evaluated by analyzing reactivity and comparing the results with those obtained with TcP2betaN. The chimera reactivity was higher than that of the peptide fractions (0.874 versus 0.564 optical density, P = 0.0017). The detectability and specificity were both 100% for the whole serum panel tested. We conclude that the obtained chimera shows an improved selectivity and sensitivity compared with other ones previously reported, therefore displaying an optimized performance for Trypanosoma cruzi infection diagnosis.
16967616 [Ankylosing spondylitis--the current situation and new therapeutic options]. 2006 Jul Ankylosing spondylitis (AS) is a chronic, immunologically mediated rheumatic disease whose progression largely depends on the extent of inflammatory activity. In contrast to rheumatoid arthritis (RA), therapeutic control of AS is very limited. Therapy of ankylosing spondylitis should not only control inflammatory processes, but also prevent structural damages and maintain the functions. Until recently, physiotherapy and non-steroidal antiphlogistics (NSA) therapy was a gold standard of AS treatment. NSA therapy alleviates inflammatory pain of spine in 60 to 80% of patients. According to the most recent findings, long-term administration of NSA can affect also X-ray progression. DMARD therapy, which is efficient in RA, has insignificant effect on axial form of AS. Sulfasalazine proved to be efficacious against peripheral form of AS; administration of MTX and leflunomide is not supported by controlled studies. Peripheral arthritis and enthesitis is usually treated by short-term application of corticoids. The fact remains that an important role in AS immunopathogenesis is played by TNF alpha whose increased levels were found in patients with AS in serum, synovial fluid and SI joints. Anti-TNF therapy with infliximab and etanercept proved to be highly efficacious in patients with AS resistant to conventional therapy. Infliximab and etanercept reduced the disease activity (50% improvement in more than half of patients), improved the function and slowed down the structural damage. MRI studies of anti-TNF therapy proved reduction of inflammatory activity in SI joints and spine. Other studies verified the efficacy of adalimumab in AS therapy and showed that adalimumab is a promising drug. Also, several randomized clinical studies proved efficacy of thalidomide whose administration, however, is limited by its severe adverse effects. Until now, the results of studies focused on pamidronate therapy appear to be rather controversial. Better understanding of AS pathogenesis led to implementation of new therapeutic procedures that significantly improve activity and functional condition of patients.
16551397 Registry of shoulder arthroplasty - the Scottish experience. 2006 Mar INTRODUCTION: Recognising that timely dissemination of information in the orthopaedic community was important and in the absence of any national guidelines for shoulder arthroplasty, the Scottish shoulder arthroplasty registry, a voluntary registry, was started in 1996. The goals of the registry were to assess contemporary practice, provide a benchmark against which surgeons could compare their practice, identify risk factors for a poor outcome, and to improve outcomes through continuous feedback to the participating surgeons. PATIENTS AND METHODS: A standardised proforma was used to collect information on the diagnostic and demographic data, type of procedure performed, type of implant used, any associated procedures performed in conjunction with the arthroplasty, and peri-operative complications. Postoperative pain, activity and patient satisfaction were assessed annually using another standardised proforma. RESULTS: Twenty surgeons have contributed to the register and 451 shoulder arthroplasties were registered over a 5-year period. Of patients, 23.2% were male and 76.8% female. The mean age was 65 years (range, 37-90 years). Shoulder arthroplasty was commonly performed for rheumatoid arthritis followed by trauma, osteoarthritis and avascular necrosis of the humeral head. Overall, 397 (88%) patients had a hemi-arthroplasty and 54 (12%) had a total shoulder replacement. Of the 54 cases that had a glenoid replacement, 28 were performed for inflammatory arthritis, 21 for osteoarthritis and 5 were for revisions. The humeral component was cemented in 204 (45%) cases, 160 of whom had a shoulder replacement for trauma. The glenoid component was cemented in 48 (89%) cases. Cross referencing our data with the figures of the actual number of shoulder arthroplasties performed, however, indicated that our registry at best collected only 53% of all the shoulder arthroplasties performed in Scotland annually. CONCLUSIONS: The value of a joint registry is dependent on the accuracy and completeness of the data entered. Our registry, therefore, fails as an implant registry. We believe that compliance for data registration can only be ensured if dedicated data collection staff are employed to co-ordinate the data collection and collation process.
18525435 Local and disseminated infections caused by Mycobacterium marinum: an unusual cause of sub 2008 Jun Mycobacterium marinum is a free-living, nontuberculous, photochromogenic mycobacterium, which can cause opportunistic infections in humans. It can cause infection through the skin that has undergone minor trauma, as the portal of entry from contaminated water, fish tanks and nonchlorinated swimming pools. It can cause skin lesions, which are either single, papulonodular lesions, confined to an extremity or may resemble cutaneous sporotrichosis. This infection can also cause deeper infections including tenosynovitis, bursitis, arthritis, and osteomyelitis. Disseminated infections and visceral involvements have been reported in immunocompromised patients. We describe 3 patients seen in Geisinger Medical Center from 2000 to 2005 in whom the diagnosis of M. marinum infection was made. All 3 patients described had sporotrichoid nodular lesions, one had a preceding minor trauma, one was initially misdiagnosed as having rheumatoid arthritis and developed disseminated infection requiring prolonged treatment, and one had direct exposure to fish and fish tank. M. marinum infection is frequently misdiagnosed probably due to its rarity of occurrence, indolent presentation and difficulty in isolation and culture. Recognition depends on a high index of suspicion and eliciting a history of aquatic exposure. Diagnosis usually requires tissue biopsy for histopathologic examination and culture.