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ID PMID Title PublicationDate abstract
15611303 The treatment of inflammatory arthritis with methotrexate in clinical practice: treatment 2005 Jan OBJECTIVE: To identify the proportion of patients with inflammatory arthritis who remain on methotrexate in the medium to long term and the incidence of side-effects in clinical practice. METHOD: The study population comprised all patients with inflammatory arthritis treated with methotrexate and monitored in clinics under the auspices of Staffordshire Rheumatology Centre. Two clinical auditors collected data retrospectively from the computer database used to support monitoring of patients on disease-modifying anti-rheumatic drugs. Information was collected on duration of treatments and reasons for stopping treatment. For patients identified as having potentially serious side-effects or who died whilst taking methotrexate, further information on their outcome was collected from patients' medical notes and where applicable post mortem reports and death registers. RESULTS: Between 1986 and 1999, 673 patients were treated with methotrexate, of whom 551 had a diagnosis of rheumatoid arthritis. From the Kaplan-Meier analysis, the probability of patients remaining on treatment 5 yr after starting methotrexate was 0.74. Three hundred and sixteen patients stopped methotrexate between 1986 and 1999. In 117 patients, the methotrexate was restarted. Seventy-two patients (10.7% of all patients) stopped because of inefficacy or patient choice or situation. Thirty-seven patients (5.5%) stopped methotrexate due to abnormal haematology (usually low neutrophils). Thirty-seven patients (5.5%) stopped methotrexate due to abnormalities in liver function tests. Life-threatening side-effects were identified in 12 patients (1.8%). These included six pneumonitis, five cytopenias and one disseminated varicella zoster. Two of these patients (0.3%) died, one from pneumonitis and one from disseminated varicella zoster. A total of 25 patients (3.7%) died while taking methotrexate and four died (0.6%) within 3 months of stopping methotrexate. One death (0.15%) was directly attributable to methotrexate (methotrexate pneumonitis). CONCLUSION: This study has shown that methotrexate is well tolerated in clinical practice in the medium to long term. It has produced accurate data on the incidence of adverse effects of methotrexate in a local population in a non-research setting. It has identified the incidence of life-threatening side-effects to be 1.7% with one death (0.15%) directly due to methotrexate. This information should prove useful when recommending such treatment to patients with inflammatory arthritis.
17015746 Serum amyloid A binding to formyl peptide receptor-like 1 induces synovial hyperplasia and 2006 Oct 15 Serum amyloid A (SAA) is a major acute-phase reactant, and has been demonstrated to mediate proinflammatory cellular responses. Although SAA has been used as an indicator for a variety of inflammatory diseases, the role of SAA in synovial hyperplasia and proliferation of endothelial cells, a pathological hallmark of rheumatoid arthritis (RA), has yet to be elucidated. In this study, we have demonstrated that SAA promotes the proliferation of human fibroblast-like synoviocytes (FLS). In addition, SAA protects RA FLS against the apoptotic death induced by serum starvation, anti-Fas IgM, and sodium nitroprusside. The activity of SAA appears to be mediated by the formyl peptide receptor-like 1 (FPRL1) receptor, as it was mimicked by the WKYMVm peptide, a specific ligand for FPRL1, but completely abrogated by down-regulating the FPRL1 transcripts with short interfering RNA. The effect of SAA on FLS hyperplasia was shown to be caused by an increase in the levels of intracellular calcium, as well as the activation of ERK and Akt, which resulted in an elevation in the expression of cyclin D1 and Bcl-2. Moreover, SAA stimulated the proliferation, migration, and tube formation of endothelial cells in vitro, and enhanced the sprouting activity of endothelial cells ex vivo and neovascularization in vivo. These observations indicate that the binding of SAA to FPRL1 may contribute to the destruction of bone and cartilage via the promotion of synoviocyte hyperplasia and angiogenesis, thus providing a potential target for the control of RA.
17159170 Should we reconsider all-polyethylene tibial implants in total knee replacement? 2006 Dec The role of modular tibial implants in total knee replacement is not fully defined. We performed a prospective randomised controlled clinical trial using radiostereophotogrammetric analysis to compare the performance of an all-polyethylene tibia with a metal-backed cruciate-retaining condylar design, PFC-Sigma total knee replacement for up to 24 months. There were 51 patients who were randomised into two treatment groups. There were 10 subsequent withdrawals, leaving 21 all-polyethylene and 20 metal-backed tibial implants. No patient was lost to follow-up. There were no significant demographic differences between the groups. At two years one metal-backed implant showed migration > 1 mm, but no polyethylene implant reached this level. There was a significant increase in the SF-12 and Oxford knee scores after operation in both groups. In an uncomplicated primary total knee replacement the all-polyethylene PFC-Sigma tibial prosthesis showed no statistical difference in migration from that of the metal-backed counterpart. There was no difference in the clinical results as assessed by the SF-12, the Oxford knee score, alignment or range of movement at 24 months, although these assessment measures were not statistically powered in this study.
16105911 Citrullination of fibronectin in rheumatoid arthritis synovial tissue. 2005 Nov OBJECTIVES: Citrullination, catalysed by peptidylarginine deiminase (PAD), is the post-translational modification of peptidylarginine to citrulline, which is intimately involved in the pathogenesis of rheumatoid arthritis (RA). Fibronectin (Fn), a large glycoprotein, is expressed at high levels in arthritic joints and it mediates various physiological processes through interactions with cell-surface integrin receptors and growth factors. We investigated the citrullination of Fn and its potential contribution to the pathogenesis of RA. METHODS: We localized Fn expression and citrullination in RA synovial tissue by immunohistochemistry, immunoprecipitation and western blotting. We also determined levels of citrullinated Fn in plasma from RA patients using sandwich enzyme-linked immunosorbent assay (ELISA). After incubating Fn with rabbit skeletal muscle PAD, we examined the binding ability of citrullinated Fn to vascular endothelial growth factor (VEGF) and integrin beta1 using a solid-phase receptor binding assay as well as the effect of the citrullinated Fn on apoptosis using cultured HL-60 cells. RESULTS: Immunohistochemistry and western blotting analysis indicated that Fn formed extracellular aggregates that were specifically citrullinated in RA synovial tissue. No Fn deposits were observed in synovial tissues of osteoarthritis (OA). Sandwich ELISA detected higher levels of citrullinated Fn in plasma from patients with RA than from healthy controls or those with systemic lupus erythematosus. Following citrullination in vitro, the affinity of Fn for VEGF increased, but binding activity to integrin beta1 decreased and Fn no longer stimulated the apoptosis of monocytes induced from cultured HL-60 cells. CONCLUSIONS: Our results suggest that the citrullination of Fn is a specific event for RA synovium, although others have detected citrullinated total proteins in inflamed synovial tissue of RA and non-RA patients. Citrullination of Fn could alter interactions between Fn and its receptors and growth factors, consequently contributing to mechanisms of RA pathogenesis such as perturbed angiogenesis and apoptosis.
17106667 [High-field and ultrahigh-field magnetic resonance imaging: new possibilities for imaging 2006 Dec Whole-body MR tomography at 3 T is moving steadily from research into routine clinical practice. The most important advantage of high-field MRI is the higher signal to noise ratio, which allows acquisitions in the musculo-skeletal system with higher resolution within the same scan time. The imaging of small joints, the visualization of labral anatomy and pathology in the shoulder and hip joints, as well as cartilage imaging will benefit from higher resolution protocols. In addition to improved morphological imaging of articular cartilage, the higher sensitivity of 3 T allows the clinical use of advanced MR techniques of cartilage such as T1 and T2 mapping, diffusion and sodium imaging. The improved spectral resolution with the higher field may improve metabolic imaging of tumors of the skeleton and soft tissues.
16127017 Do we need new treatment that goes beyond tumor necrosis factor blockers for rheumatoid ar 2005 Jun Rheumatoid arthritis (RA) has a prevalence of approximately 1%, making it the most common inflammatory rheumatic disease. The outcome for RA patients has significantly improved during recent years. Factors include the introduction of new therapies such as tumor necrosis factor (TNF)-blocking agents and new treatment strategies, especially early and aggressive therapy, including combinations of several disease-modifying antirheumatic drugs (DMARDs). However, only 60-70% of RA patients respond to treatment with a TNF-blocking agent. In addition, most of these patients show only a partial response according to ACR20 criteria. Therefore, to ameliorate painful joint inflammation and prevent disability in RA patients, new treatment principles and more intelligent combination therapies are urgently needed. Interestingly, the strategy of switching patients who no longer respond to one of the TNF blockers to another has often turned out to be effective. Areas of ongoing research include combining TNF-blocking agents with DMARDs other than methotrexate. Also, several new biologics are being tested in clinical trials that promise to soon enhance the therapeutic armamentarium to fight RA. These biologics' mechanisms of action feature blockade of T cell costimulation by a CTLA4Ig fusion protein (abatacept); blockade of interleukin (IL)-6 signaling with an antibody to the IL-6 receptor (MRA); neutralizing IL-15 by a monoclonal antibody; and targeting B cells with an anti-CD20 antibody (rituximab). Other therapeutic approaches, such as blockade of chemokine receptors, adhesion molecules, complement components, and transcription factors regulating the inflammatory response, appear promising; however, they still need careful evaluation in placebo-controlled clinical studies.
15707475 Etanercept in arthritis. 2005 Jan Tumour necrosis factor-alpha (TNF-alpha) is one of the inflammatory cytokines. It is released by activated monocytes, macrophages and T lymphocytes and promotes inflammation. TNF-alpha binds to two receptors; one of these is the type 2 TNF receptor (p75). Etanercept is a soluble TNF-receptor fusion protein. It consists of two linked dimmers, each with a ligand-binding portion of the higher affinity type 2 TNF receptor (p75). This fusion protein binds to TNF-alpha and prevents it from interacting with its receptor. Etanercept is given by subcutaneous administration at a dose of 25 mg twice a week. This dosing reflects its half-life of about 4 days. Clinical trials show etanercept is effective and safe to use in rheumatoid arthritis (RA). It reduces disease activity and limits progressive joint damage in both early and late disease. It can be used as a monotherapy or in combination with methotrexate, and in this, the latter approach appears most effective. It is also effective in psoriatic arthritis and ankylosing spondylitis. Although the biologic appears safe, caution is needed to ensure it does not re-activate tuberculosis. It should not be used in patients with disseminated sclerosis, and there are concerns about a potential relationship to lymphoma. Its high cost means there will be continuing debate about the ideal position of this new biologic within the treatment pathway of RA. At present, it is recommended for use when methotrexate and another disease-modifying drug have failed.
15901903 Methotrexate-induced pancytopenia: serious and under-reported? Our experience of 25 cases 2005 Aug OBJECTIVE: To ascertain the extent of methotrexate (MTX)-related pancytopenia at the Norfolk and Norwich University Hospital (NNUH) between 1999 and 2004. METHODS: Patients were identified by a department database search, review of pharmacy records and personal communication. Pancytopenia was defined as white blood cell count (WBC) <3.5 x 10(9)/l, haemoglobin (Hb) <11 g/dl and platelet count <130 x 10(9)/l. Severe pancytopenia was defined as WBC <2.0 x 10(9)/l, Hb <10 g/dl and platelet count <50 x 10(9)/l. RESULTS: Twenty-five patients had MTX-induced pancytopenia. Eleven patients were taking folic acid and one folinic acid. The median dose of MTX was 12.5 mg weekly (interquartile range 5.625 mg) and median duration of treatment 36 months (interquartile range 40.5 months). The severity of pancytopenia correlated with the dose (P = 0.04). The numbers of patients with potential risk factors were: renal insufficiency, 8; pre-existing folate deficiency, 7; age >75 yr, 15; hypoalbuminaemia, 18; pre-existing infection with hip prosthesis, 1; possible drug interactions, 18; dosing errors, 1; and polypharmacy, 15. Pancytopenia was detected by routine blood monitoring in nine patients. There were seven deaths (28% mortality), five from sepsis and two from acute myeloid leukaemia. CONCLUSION: This is the largest reported individual case series of MTX-induced pancytopenia. With the increasing long-term use of MTX, it is important that patients be monitored for haematological side-effects as pancytopenia can be a late manifestation. Pharmacogenetics may hold the answer to predicting who is at risk of this potentially fatal complication of MTX.
15743471 Effect of adalimumab on neutrophil function in patients with rheumatoid arthritis. 2005 Neutrophils are known to be targets for the biological activity of tumour necrosis factor (TNF)-alpha in the pathogenesis of rheumatoid arthritis (RA). Therefore, these cells may be among the targets of anti-TNF-alpha therapy. In this study we evaluated the effect of therapy with adalimumab (a fully human anti-TNF-alpha mAb; dosage: 40 mg subcutaneously every other week) on certain phenotypic and functional aspects of neutrophils obtained from 10 selected patients with RA and 20 healthy control individuals. Peripheral blood neutrophils were obtained at baseline and during anti-TNF-alpha therapy (2, 6 and 12 weeks after the first administration of adalimumab). All patients had been receiving a stable regimen of hydroxychloroquine, methotrexate and prednisone for at least 3 months before and during the study. Baseline neutrophil chemotaxis was significantly decreased in RA patients when compared with control individuals (P < 0.001). Two weeks after the first administration of adalimumab, chemotactic activity was completely restored, with no differences noted between patients and control individuals; these normal values were confirmed 6 and 12 weeks after the start of anti-TNF-alpha therapy. Phagocytic activity and CD11b membrane expression on neutrophils were similar between RA patients and control individuals; no modifications were observed during TNF-alpha neutralization. The production of reactive oxygen species, both in resting and PMA (phorbol 12-myristate 13-acetate)-stimulated cells, was significantly higher in RA patients at baseline (P < 0.05) and was unmodified by anti-TNF-alpha mAb. Finally, we showed that the activation antigen CD69, which was absent on control neutrophils, was significantly expressed on neutrophils from RA patients at baseline (P < 0.001, versus control individuals); however, the molecule was barely detectable on cells obtained from RA patients during adalimumab therapy. Because CD69 potentially plays a role in the pathogenesis of arthritis, our findings suggest that neutrophils are among the targets of anti-TNF-alpha activity in RA and may provide an insight into a new and interesting mechanism of action of anti-TNF-alpha mAbs in the control of inflammatory arthritis.
15550531 Tolerance and short term efficacy of rituximab in 43 patients with systemic autoimmune dis 2005 Jun OBJECTIVE: To assess the tolerance and efficacy of rituximab in patients with various autoimmune diseases seen in daily rheumatological practice. METHODS: 866 rheumatology and internal medicine practitioners were contacted by e-mail to obtain the files of patients treated with rituximab for systemic autoimmune diseases. Patients with lymphoma were analysed if the evolution of the autoimmune disease could be evaluated. RESULTS: In all, 43 of 49 cases could be analysed, including 14 with rheumatoid arthritis (RA), 13 with systemic lupus erythematosus (SLE), six with primary Sjogren's syndrome (pSS), five with systemic vasculitis, and five with other autoimmune diseases. Rituximab was prescribed for lymphoma in two patients with RA and two with pSS. In the 39 other cases, rituximab was given because of the refractory character of the autoimmune disease. The mean follow up period was 8.3 months (range 2 to 26). There were 11 adverse events in 10 patients and treatment had to be discontinued in six. Efficacy was observed in 30 patients (70%): RA 11, SLE 9, pSS 5, vasculitis 2, antisynthetase syndromes 2, sarcoidosis 1. The mean decrease in corticosteroid intake was 9.5 mg/d (range 0 to 50) in responders. Seven patients experienced relapse after mean 8.1 months (5 to 15). Three patients died because of refractory autoimmune disease. CONCLUSIONS: Despite absence of marketing authorisation, rituximab is used to treat various refractory autoimmune diseases in daily rheumatological practice. This study showed good tolerance and short term clinical efficacy, with marked corticosteroid reduction in patients with SLE, pSS, vasculitis, and polymyositis.
17474177 [Diagnostic difficulties in polymyositis]. 2006 Polymyositis is a connective tissue disease. Although myositis is the dominant clinical manifestation, internal organs may also be affected. Arthritis occurs in 30% of patients, especially in the course of the anti-synthetase syndrome. We report on a case of a woman with polymyositis and interstitial lung disease. Arthritis and the presence of anti-cyclic citrullinated peptide antibodies in the patient's serum may suggest the diagnosis of the overlap syndrome.
16900373 Defensins- and cathepsin G-ANCA in systemic lupus erythematosus. 2006 Dec In this study, we examined the content of antineutrophil cytoplasmic antibodies (ANCA) against defensins and cathepsin G in sera from systemic lupus erythematosus (SLE) patients and their significance in estimating the activity of SLE. Defensins- and cathepsin G-ANCA in sera from 28 patients with SLE, eight patients with rheumatoid arthritis (RA) and eight patients with microscopic polyangitis (mPA) were measured by ELISA. Significantly increased defensins- and cathepsin G-ANCA were found in sera of patients with SLE and mPA when compared with the value of normal controls. Though significantly higher defensins- and cathepsin G-ANCA were detected in both active and inactive SLE patients, the value in active SLE patients was significantly higher than inactive SLE patients. After the therapy with high dose of prednisolone, the serum level of defensins- and cathepsin G-ANCA was decreased, and this decrease was sustained for at least 16 weeks. This study suggests that defensins- and cathepsin G-ANCA may serve as useful markers of the disease activity of SLE.
16900293 A tale of two citrullines--structural and functional aspects of myelin basic protein deimi 2007 Feb Myelin basic protein (MBP) binds to negatively charged lipids on the cytosolic surface of oligodendrocyte membranes and is responsible for adhesion of these surfaces in the multilayered myelin sheath. The pattern of extensive post-translational modifications of MBP is dynamic during normal central nervous system (CNS) development and during myelin degeneration in multiple sclerosis (MS), affecting its interactions with the myelin membranes and with other molecules. In particular, the degree of deimination (or citrullination) of MBP is correlated with the severity of MS, and may represent a primary defect that precedes neurodegeneration due to autoimmune attack. That the degree of MBP deimination is also high in early CNS development indicates that this modification plays major physiological roles in myelin assembly. In this review, we describe the structural and functional consequences of MBP deimination in healthy and diseased myelin.
17139865 [Shoulder pain: imaging examinations]. 2006 Sep 30 Non-traumatic shoulder pain is a diagnostic challenge for clinicians. Usually, the clinical examination is supplemented by nowadays well-defined imaging studies. Radiography is the first examination to be requested on a systematic basis. It always includes several views to study the whole scapular region (glenohumeral joint, subacromial space, acromioclavicular joint etc.). If the radiographic examination is not precise enough, a noninvasive and non-irradiating examination is performed, either ultrasonography or magnetic resonance imaging. The latter seems to be more comprehensive than ultrasonography. However, the usefulness of the association radiography-ultrasonography should be emphasized: both examinations are perfectly complementary, inexpensive and easy to access. Invasive examinations, such as CT arthrography, are still too often requested following a radiological examination. Since they do not investigate the whole shoulder, they should be limited to the investigation of specific diseases, often as part of presurgical assessments required for or by the orthopedic surgeon.
15934068 Increased intraarticular interleukin-7 in rheumatoid arthritis patients stimulates cell co 2005 Jun OBJECTIVE: To determine the level of intraarticular expression of interleukin-7 (IL-7) in patients with rheumatoid arthritis (RA) and to investigate the mechanisms by which IL-7 facilitates activation of CD4(+) T cells and monocyte/macrophages in RA. METHODS: IL-7 levels were measured in synovial fluid obtained from patients with RA and patients with osteoarthritis (OA). Immunohistologic analysis was used to assess the expression of IL-7 in synovial tissue from patients with RA. Proliferation and activation markers were determined in order to measure the effect of IL-7 on mononuclear cells, isolated CD4(+) T cells, and monocyte/macrophages from the peripheral blood and synovial fluid. Cocultures of CD4(+) T cells and monocytic cells in the absence or presence of a semipermeable membrane were performed to assess the extent to which IL-7 induces its effects, either contact dependently or via soluble mediators. RESULTS: IL-7 levels were increased in synovial fluid from patients with RA compared with the levels in synovial fluid from patients with OA. Macrophages, fibroblasts, and endothelial cells in the joint lining tissue expressed abundant IL-7. In vitro, synovial fluid CD4(+) T cells and macrophages were hyperresponsive to IL-7 when compared with peripheral blood cells. Furthermore, IL-7 enhanced cell contact-dependent activation of CD4(+) T cells and monocyte/macrophages. CONCLUSION: The abundant intraarticular expression of IL-7 and the stimulation by IL-7 of contact-dependent activation of CD4(+) T cells and monocytic cells indicate that this cytokine plays an important proinflammatory role in RA synovitis. Further identification of IL-7-induced pathways may improve understanding of the important interactive role of CD4(+) T cells and monocytic cells in RA.
15647441 Activation markers of peripheral blood mononuclear cells in late pregnancy and after deliv 2005 Feb OBJECTIVE: To study the putative shift of a Th1 to a Th2 immune response in pregnancy and its reversal post partum in healthy women and patients with rheumatoid arthritis (RA). METHODS: Peripheral blood mononuclear cells (PBMC) were examined by FACS analysis for the expression of activation markers CD25 and HLA-DR and chemokine receptors CXCR3 and CCR4 on CD4+ and CD8+ T cells in four healthy women and four patients with RA. Samples were analysed once in the third trimester and six and 12 weeks post partum. Eight healthy non-pregnant women served as controls. RESULTS: No reduction of CD25 and HLA-DR+ T cells occurred in the third trimester, but a significant increase was observed post partum in healthy women and an even greater increase in patients. Proportions of T cells expressing the CXCR3 or CCR4 marker were similar in patients and controls during pregnancy, whereas a significant increase occurred post partum. The ratio of CXCR3+ to CCR4+ cells remained unchanged during the observation period and did not differ significantly from that in non-pregnant controls. CONCLUSION: A shift from a Th1 to a Th2 immune response was not detected in the circulation of healthy pregnant women or pregnant patients. The significant increase of T cell activation after pregnancy warrants further investigation into the mechanisms of adjustment of the immune system post partum and its clinical correlates in rheumatic patients.
16716139 Leflunomide and warfarin interaction: case report and review of the literature. 2006 Jun A 61-year-old Caucasian woman receiving long-term anticoagulation with warfarin for recurrent thromboembolism and atrial fibrillation was found to have an elevated international normalized ratio (INR) after she started leflunomide therapy for rheumatoid arthritis. Her INR had been stable for 4 months before this event. The patient required an overall decrease of 22% in her weekly warfarin dose to maintain a therapeutic INR within the goal range of 2.0-3.0 after adding leflunomide therapy. A comprehensive PubMed/MEDLINE search was conducted to identify literature addressing the potential interaction between warfarin and leflunomide. Evidence describing the interaction and its potential mechanism was limited to one published case report and to in vitro data, respectively. Our case report provides additional support that such an interaction exists and that it was at least partly responsible for the subsequent increase in the patient's INR. Therefore, continued evaluation and documentation of this potential drug interaction is imperative. To reduce the risk of adverse effects related to excessive anticoagulation with the start of leflunomide in patients taking warfarin, clinicians should increase their frequency of INR monitoring and adjust the warfarin dosage accordingly to maintain therapeutic anticoagulation.
16088245 Risk of retinal vein occlusions in patients treated with rofecoxib (vioxx). 2005 Jul AIMS: To present patients with branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) after application of rofecoxib (Vioxx), a cyclo-oxygenase (COX) 2 inhibitor. METHODS: Three patients with sudden decrease in their vision were referred for evaluation and possible treatment. RESULTS: A 72-year-old female with rheumatoid arthritis was treated with rofecoxib. When the dosage was doubled to 50 mg daily, she noticed a sudden painless decrease of vision in her right eye. Her visual acuity (VA) was 20/400 OD and 20/20 OS. Biomicroscopy OD demonstrated a CRVO with tortuous retinal veins and numerous flecked hemorrhages in the midperiphery. A 68-year-old female with severe osteoporosis developed a BRVO with flame-shaped hemorrhages in the superior hemisphere OS 1 day after taking rofecoxib (25 mg) daily. A 47-year-old American male took Vioxx for 1 week to relieve hip pain and noticed temporarily decreased vision OD. A month later, he resumed taking Vioxx and noticed a progressive decline in his VA with persistent cloudiness. Ophthalmic examination revealed a CRVO in his right eye. CONCLUSION: Although COX-2 inhibitors are safe in the majority of patients, under certain conditions they may induce prothrombotic effects. Few patients with predisposed thrombosis may be at risk for cardiovascular and ocular thrombotic events.
16848103 Rehabilitation following total shoulder arthroplasty. 2005 Dec Total shoulder arthroplasty (TSA) is a standard operative treatment for a variety of disorders of the glenohumeral joint. Patients, who have continued shoulder pain and loss of function in the presence of advanced joint pathology, despite conservative management, are often managed by undergoing a TSA. The overall outcomes that are reported after surgical intervention are quite good and appear to be primarily determined by the underlying pathology and the tissue quality of the rotator cuff. The current Neer protocol for postoperative TSA rehabilitation is widely used and based on tradition and the basic science of soft tissue and bone healing. The purpose of this paper is to review the indications for TSA, focusing on the underlying pathologies, and to describe the variables that impact the rehabilitation program of individuals who have had a TSA. A postoperative TSA rehabilitation protocol and algorithm, founded on basic science principles and tailored toward the specific clinical condition, are presented.
16916546 Investigating disease susceptibility and the negative correlation of schizophrenia and rhe 2006 Sep 30 Schizophrenia and rheumatoid arthritis (RA) are both chronic diseases with an estimated genetic component of 60%. While RA is a well-known autoimmune inflammatory joint disease, recent data point to an active immune process also being involved in schizophrenia. Several studies confirmed the negative association between schizophrenia and RA, indicating genetic factors that predispose to the one disorder, while protecting from the other. Macrophage migration inhibitory factor (MIF) and the monocytes surface receptor CD14 are involved in the development and maintenance of chronic inflammation. We therefore investigated if the -G173C single nucleotide polymorphism (SNP) and the tetranucleotide repeat CATT (5 - 8) at position -794 of the MIF gene and the CD14 - C159T transition are candidates for genetic liability to schizophrenia and RA or could explain the negative association between them. In our study 157 schizophrenic patients, 119 patients suffering from RA, and 225 healthy individuals were genotyped. All subjects were Caucasians. The CD14- and MIF-genotypes were equally distributed in all three groups. From our results, we cannot confirm the hypothesis that the investigated genetic mutations within the MIF and/or the CD14 gene are involved in the aetiology of either disease or could explain the negative correlation of schizophrenia and RA.