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ID PMID Title PublicationDate abstract
17218170 Pyrolytic carbon proximal interphalangeal joint arthroplasty: results with minimum two-yea 2007 Jan PURPOSE: To retrospectively review the surgical technique, postoperative therapy/splinting protocols, and clinical and radiographic outcomes of patients who had pyrolytic carbon proximal interphalangeal (PIP) joint arthroplasty. METHODS: A total of 50 PIP joint replacements in 35 patients were performed with a minimum follow-up period of 27 months. Indications for surgery included pain, decreased range of motion, instability, and/or deformity. The preoperative diagnosis was osteoarthritis in 14, rheumatoid arthritis in 11, and posttraumatic arthritis in 10. There were 20 women and 15 men affected. The average age at the time of surgery was 53 years. The fingers replaced included the index (15), middle (18), ring (10), and small (7). The preoperative arc of motion averaged 40 degrees (0 degrees-60 degrees ), and the pinch and grip measurements averaged 3 and 19 kg, respectively. The preoperative pain scores averaged 6 (scale, of 0-10) on a visual analog space scale. RESULTS: The arc of motion was 47 degrees after surgery, and the average pinch and grip measurements were 4 and 25 kg, respectively. Pain scores improved to 1. At the final follow-up evaluation the overall patient satisfaction was nearly 80%. The results of index finger PIP replacements are compatible with other digits. Fourteen joints (in 14 patients) to date have required additional procedures to improve or maintain joint motion/function or pain; 5 for minor reasons and 9 for major complications. The revision arthroplasty rate was 8%. No infections were noted. Although not medically necessary, 2 patients requested and had an amputation. Radiographic subsidence and subsequent settling (in accordance with Wolff's law) without apparent loosening occurred in 20 joints. CONCLUSIONS: Our 2-year minimum follow-up evaluation of pyrolytic carbon implant arthroplasty showed improved pain relief and good overall patient satisfaction. Twenty-eight percent of patients required a second procedure and 8% required a revision arthroplasty. Radiographs showed gross changes in implant and eventual settling to a stable position in 40% of the joints. A longer follow-up period will help to better determine the efficacy of this implant. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level IV.
18383358 The influence of age at symptom onset and length of followup on mortality in patients with 2008 Apr OBJECTIVE: To investigate the influence of age at symptom onset and length of followup on mortality in patients with recent-onset inflammatory polyarthritis (IP), and to examine predictors of mortality in relation to disease duration. METHODS: From 1990 to 1994, patients with recent-onset IP were registered with the Norfolk Arthritis Register (NOAR) and followed up prospectively. Standardized mortality ratios (SMRs) were calculated for all-cause and cardiovascular disease (CVD) mortality and for those who were younger than age 55 years at disease onset and for the first 5 and 10 years of followup. Cox proportional hazards models were developed to assess predictors of early and later mortality. RESULTS: Of 1,098 patients, 224 (20%) had died by the end of 2004. All-cause and CVD mortality were increased in rheumatoid factor (RF)-positive patients and in this subgroup, CVD mortality was increased at both early and later followup (SMR 5-year followup 1.93 [95% confidence interval 1.08-3.19]; SMR 10-year followup 2.00 [95% confidence interval 1.37-2.80]). CVD mortality was highest in seropositive patients<55 years of age at disease onset (SMR 5.58 [95% confidence interval 2.24-11.50]). In multivariate models, age at onset, male sex, RF positivity, Health Assessment Questionnaire score>or=1.5, and nodules were predictors of early and later mortality. CONCLUSION: Patients with IP had higher rates of CVD mortality throughout the followup period studied, and this was highest in seropositive patients who were <55 years of age at symptom onset. This subgroup deserves particular attention in terms of disease and risk factor modification. Nodules were independent predictors of CVD mortality, suggesting that extraarticular/vascular inflammation identifies patients at particularly high CVD risk.
16673808 Non-sarcoidal, non-tuberculoid granuloma in common variable immunodeficiency. 2006 Apr Sarcoidal (non-caseating) or tuberculoid granulomas are cutaneous manifestations of common variable immunodeficiency (CVID). In this case report, we describe a patient with CVID but with non-sarcoidal, non-tuberculoid granuloma. The 29-year-old Egyptian male patient presented with a vitiliginous patch on the chin of 1 year duration and multiple recurrent warts on the hands and feet of 8 years duration. He is a known case of CVID with chronic diarrhea, recurrent otitis media, pneumonia, purulent conjunctivitis, septic arthritis, hepato-splenomegaly, and generalized lymphadenopathy. In addition, he had evidence of multiple non-tender subcutaneous nodules predominantly juxta-articular and recurrent rheumatoid-like arthritis. The skin overlying the nodules was either normal or slightly erythematous. Laboratory findings revealed markedly reduced serum immunoglobulins (IgG 3.4, n = 7.2-16.9 g/l; IgA 0.1, n = 0.69-3.82 g/l and IgM 0.1, n = 0.63-2.77 g/l) and deficient T cell function. Histopathologic examination of a skin nodule showed well demarcated areas of fibrinoid degeneration of collagen that stain homogeneously and are surrounded by histiocytes in a palisading arrangement, suggestive of granuloma annulare. No microorganisms could be detected. Serology for rheumatoid factor and HIV infection has been persistently negative. Although most infections, including common warts responded well to intravenous immunoglobulin replacement therapy (12 g/i.v., every 2 weeks) and oral broad spectrum antibiotic therapy, the subcutaneous nodules persisted. The vitiliginous patch responded favorably and disappeared within 24 local PUVA sessions. Since skin nodules are asymptomatic, no further treatment was given.
18025155 Bmx tyrosine kinase regulates TLR4-induced IL-6 production in human macrophages independen 2008 Feb 15 Chronic inflammation, as seen in conditions such as rheumatoid arthritis and Crohn disease, is in part driven by discordant production of inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6 (IL-6). Tyrosine kinase activity is essential to lipopolysaccharide-induced cytokine production in monocytes, and previous studies by us and others have implicated a role for the Tec kinase Bruton's tyrosine kinase (Btk) in inflammatory cytokine production. Here we show that knockdown of Btk using RNA interference results in decreased tumor necrosis factor-alpha, but not IL-6 production. Further investigations into the signaling mechanisms regulating IL-6 production led to the discovery that the Tec kinase bone marrow tyrosine kinase gene in chromosome X (Bmx) regulates Toll-like receptor-induced IL-6 production. Our data further showed that Bmx-dependent super-induction of IL-6 does not involve nuclear factor-kappaB activity. More detailed investigations of pathways downstream of Bmx signaling revealed that Bmx targets the IL-6 3' untranslated region to increase mRNA stabilization via a novel, thus far undefined, p38 mitogen activated protein kinase-independent pathway. These data have important implications for the design of therapeutics targeted against specific cytokines and their regulators in inflammatory disease.
17451498 Salivary gland parameters and clinical data related to the underlying disorder in patients 2007 Apr This study assessed salivary gland parameters and clinical data in patients referred to our clinic because of persisting xerostomia of unknown origin, in order to facilitate early diagnosis and recognition of the underlying disorder. Most patients were referred for diagnostic analysis of a possible Sjögren's syndrome (SS). A complete diagnostic work-up was available in all patients (n = 176), including data on salivary gland function, saliva composition, sialography, salivary gland swelling, pattern of complaints, general health, and medication. Patients were diagnosed with SS (n = 62), sialosis (n = 45), sodium retention syndrome (n = 30), or medication-induced xerostomia (n = 9). In 30 patients no disease related to salivary gland pathology was found. Unstimulated whole salivary flow was decreased in all patients, except in patients with sodium retention syndrome and in patients without salivary gland pathology. Submandibular/sublingual salivary flow was lowest in SS patients. SS and sialosis patients had increased salivary potassium concentrations, whereas only SS patients had increased sodium concentrations. About half of the sialosis patients mainly complained of persistent parotid gland swelling. Xerostomia-inducing medication was used by most patients. It was concluded that gland-specific sialometry and sialochemistry is useful in discriminating between the various disorders causing persisting xerostomia.
17442501 Can low dose diagnostic dental radiation trigger Sjögren's syndrome? 2007 Sjögren's syndrome (SS), first described by Swedish ophthalmologist Henrik Sjögren in 1930, is a chronic inflammatory, autoimmune disorder characterized by diminished lacrimal and salivary glands secretion resulting in keratoconjunctivitis sicca and xerostomia. One factor instrumental in severe salivary gland damage and salivary flow decrement is radiation therapy. Apoptosis, implicated in autoimmune diseases, has been shown to be responsible for this damage. However, there are no studies investigating the effect of diagnostic radiation (low dose) on salivary glands. A safe level of radiation has not been established thus far. Diagnostic radiation has been used from 1896, but generally applied only from 1916. Dr. Sjögren identified SS in 1930. It is possible that the introduction of X-rays for diagnostic purposes is associated with SS onset. Available data show drastically reduced use of diagnostic dental radiation in developing countries and a concomitantly drastically reduced or lack of SS in these countries. In countries like India with a population of 1.1 billion (health care level II country), primary SS has been reported to be rare (total of 27 and 23 primary SS and secondary SS patients respectively reported thus far), while a health care level I country like USA, with a population of 300 million, there are about 2-4 million SS patients. Health care level IV countries do not have a single reported case of SS. There is also evidence for ultraviolet radiation inducing subcutaneous lupus erythematosus, an autoimmune disorder. We hypothesize that diagnostic dental radiation could be a factor for the development of SS as a result of either radiation induced apoptosis or through oxidative modification of proteins.
18283632 The promise of Hox11+ stem cells of the spleen for treating autoimmune diseases. 2008 Feb The spleen of human adults uniquely possesses a reservoir of multilineage adult stem cells that express the developmental transcription factor HOX11. In contrast to hematopoietic stem cells, HOX11+ stem cells hold potentially broader therapeutic applications because they are less lineage restricted. HOX11/TLX1 is part of a homeodomain gene family essential for organogenesis of the spleen and for contributions to development of hindbrain, cochlea, pancreas, salivary glands, among other organs and tissues. While HOX11/TLX1 displays widespread patterns of expression during embryogenesis, its expression was thought to cease after birth. Recent findings in human post-mortem tissue have shattered this dogma, finding that HOX11/TLX1 stem cells are uniquely and abundantly expressed throughout adulthood in the human spleen. While their role in humans is not yet understood, HOX11/TLX1 stem cells from the spleen of normal mice have been harvested to assist in both the treatment and cure at least two autoimmune diseases: type 1 diabetes, Sjogren's syndrome, and possibly their comorbid hearing loss. The splenic stem cells are infused, with an immune therapy, into diseased NOD mice, where they can home to the diseased organ, differentiate into the appropriate cell type, and assume normal functioning with the endogenous regeneration of the animal due to disease removal. This review covers HOX11/TLX1+ stem cells' success in an animal model and their potential for treating autoimmune diseases in organs that mirror their extensive expression patterns during embryogenesis.
15916807 Structural, functional and immunologic characterization of folded subdomains in the Ro52 p 2006 Feb Ro52, one of the major autoantigens in the rheumatic disease Sjögren's syndrome (SS), belongs to the tripartite motif (TRIM) or RING-B-box-coiled-coil (RBCC) protein family, thus comprising an N-terminal RING, followed by a B-box and a coiled-coil region. Several different proteomic functions have been suggested for Ro52, including DNA binding, protein interactions and Zn(2+)-binding. To analyze the presence and/or absence of these functions and, in particular, map those to different subregions, the modular composition of the Ro52 protein was experimentally characterized. Two structured parts of Ro52 were identified, corresponding to the RING-B-box and the coiled-coil regions, respectively. Secondary structure analysis by circular dichroism (CD) spectroscopy indicated that the two subregions are independently structured. The entire RING-B-box region displayed Zn(2+)-dependent stabilization against proteolysis in the presence of Zn2+, indicating functional Zn(2+)-binding sites in both the RING and the B-box. However, no stabilization with DNA was detected, irrespective of Zn(2+), thus suggesting that the RING-B-box region does not bind DNA. Oligomerization of the coiled-coil was investigated by analytical ultracentrifugation and in a mammalian two-hybrid system. Both methods show weak homodimer affinity, in parity with other coiled-coil domains involved in regulatory interactions. The C-terminal B30.2 region was rapidly degraded both during cellular expression and refolding, indicating a less stable structure. Immunologic analysis of the stable protein regions with sera from patients with Sjögren's syndrome shows that immunodominant epitopes to a large extent are localized in the structurally stable parts of Ro52. The results form a basis for further Ro52 functional studies on the proteome level.
17008549 Annexin-1 modulates T-cell activation and differentiation. 2007 Feb 1 Annexin-1 is an anti-inflammatory protein that plays an important homeostatic role in innate immunity; however, its potential actions in the modulation of adaptive immunity have never been explored. Although inactive by itself, addition of annexin-1 to stimulated T cells augmented anti-CD3/CD28-mediated CD25 and CD69 expression and cell proliferation. This effect was paralleled by increased nuclear factor-kappaB (NF-kappaB), nuclear factor of activated T cells (NFATs), and activator protein-1 (AP-1) activation and preceded by a rapid T-cell receptor (TCR)-induced externalization of the annexin-1 receptor. Interestingly, differentiation of naive T cells in the presence of annexin-1 increased skewing in Th1 cells; in the collagen-induced arthritis model, treatment of mice with annexin-1 during the immunization phase exacerbated signs and symptoms at disease onset. Consistent with these findings, blood CD4+ cells from patients with rheumatoid arthritis showed a marked up-regulation of annexin-1 expression. Together these results demonstrate that annexin-1 is a molecular "tuner" of TCR signaling and suggest this protein might represent a new target for the development of drugs directed to pathologies where an unbalanced Th1/Th2 response or an aberrant activation of T cells is the major etiologic factor.
17192555 Hypothalamic-pituitary-adrenal axis function in Sjögren's syndrome: mechanisms of neuroen 2006 Nov To date, evidence suggests that rheumatic diseases are associated with hypofunctioning of the hypothalamic-pituitary-adrenal (HPA) axis. Sjögren's syndrome (SS), the second most common autoimmune disorder, is characterized by diminished lacrimal and salivary gland secretion. To examine HPA axis activity in SS patients, the adrenocorticotropin (ACTH) response to ovine corticotropin-releasing factor (oCRH) was used as a direct measure of corticotrophic function, and the plasma cortisol response to the ACTH released during oCRH stimulation as an indirect measure of adrenal function. Significantly lower basal ACTH and cortisol levels were found in patients with SS and were associated with a blunted pituitary and adrenal response to oCRH compared to normal controls. Fibromyalgia (FM) patients demonstrated elevated evening basal ACTH and cortisol levels and a somewhat exaggerated peak, delta, and net integrated ACTH response to oCRH. A subgroup of SS patients also met the diagnostic criteria for FM and demonstrated a pituitary-adrenal response that was intermediate to SS and FM. These findings suggest not only adrenal axis hypoactivity in SS and FM patients, but also that varying patterns of adrenal and thyroid axes dysfunction may exist in patients with different rheumatic diseases.
16309672 Effect of inflammation on lacrimal gland function. 2006 May The lacrimal gland is the main contributor to the aqueous layer of the tear film. It secretes proteins, electrolytes and water, which helps to nourish and protect the ocular surface. Lacrimal gland secretion is primarily under neural control, which is achieved through a neural reflex arc. Stimuli to the ocular surface activate afferent sensory nerves in the cornea and conjunctiva. This in turn activates efferent parasympathetic and sympathetic nerves in the lacrimal gland to stimulate secretion. Sex steroid hormones are also important regulators of lacrimal gland functions. A decrease or lack of lacrimal gland secretion is the leading cause of aqueous tear deficient dry eye syndrome (DES). It has been suggested that DES is an inflammatory disorder that affects the ocular surface and the lacrimal gland. In several pathological instances, the lacrimal gland can become a target of the immune system and show signs of inflammation. This can result from autoimmune diseases (Sjögren's syndrome), organ transplantation (graft versus host disease), or simply as a result of aging. The hallmarks of lacrimal gland inflammation are the presence of focal lymphocytic infiltrates and increased production of proinflammatory cytokines. The mechanisms leading to lacrimal gland dysfunction are still poorly understood. Apoptosis, production of autoantibodies, hormonal imbalance, alterations in signaling molecules, neural dysfunction, and increased levels of proinflammatory cytokines have been proposed as possible mediators of lacrimal gland insufficiency in disease states.
19085295 Lacrimal fossa lesions: pictorial review of CT and MRI features. 2008 A wide range of disease process involve the lacrimal gland/fossa. In this pictorial review, we use histology-proven cases to illustrate conditions that affect the lacrimal gland/fossa. CT and MRI features of neoplastic, inflammatory, infiltrative, and developmental conditions are discussed.
17457192 Interleukin-6 and tumor necrosis factor-alpha levels in tears of patients with dry eye syn 2007 May PURPOSE: To determine the levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in tears of patients with dry eye syndrome. METHODS: IL-6 and TNF-alpha levels were measured by enzyme-linked immunosorbent assay in tear samples obtained from 18 patients with dry eye (8 patients with Sjögren syndrome and 10 patients with non-Sjögren syndrome) and 14 control subjects. The correlation between IL-6 and TNF-alpha levels and tear film and ocular surface parameters was analyzed. The relative expression of these cytokines was evaluated in conjunctival impression cytology and conjunctival biopsy specimens by using immunohistochemical staining. RESULTS: The mean levels of IL-6 and TNF-alpha were, respectively, 18.57 +/- 8.92 and 3.68 +/- 3.45 pg/mL in patients with dry eye and 3.59 +/- 3.38 (P < 0.01) and < 0.5 (P < 0.01) pg/mL in control subjects. IL-6 level was significantly increased in tears of patients with Sjögren syndrome compared with those with non-Sjögren syndrome (P < 0.01). IL-6 level correlated significantly with tear film breakup time (P = 0.04), Schirmer test (P < 0.01), tear clearance (P = 0.02), keratoepithelioplasty score (P < 0.01), and goblet cell density (P = 0.03), but not with corneal sensitivity (P = 0.08). There was no significant difference in TNF-alpha level between patients with non-Sjögren and Sjögren syndrome. TNF-alpha levels did not correlate with tear film and ocular surface parameters. Immunohistochemical staining showed positive staining for IL-6 in specimens from patients with dry eye, especially in specimens from patients with Sjögren syndrome. CONCLUSION: IL-6 and TNF-alpha levels are elevated in tears of patients with dry eye syndrome. IL-6 level, but not TNF-alpha level, is associated with the severity of the disease and correlates with various tear film and ocular surface parameters.
17137683 [Update in Hepatitis C virus associated extrahepatic manifestations]. 2007 Jun INTRODUCTION: Since the discovery of the hepatitis C virus, many manifestations, so called extra-hepatic manifestations (EHM), are largely reported with more or less relationship proofs. ACTUALITIES AND MAIN POINTS: This article proposes a review of the main extra-hepatic manifestations associated with the Hepatis C Virus infection and which remain a topical subject, more than fifteen years after the discovery of this virus. Mixed cryoglobulin and its vasculitic manifestations are still one of the more frequent Hepatis C Virus associated-extra-hepatic manifestations. Its management may be critically changed due to the increasing use of anti-CD20 therapy. Among other HCV-EHM, the following extra-hepatic manifestations are still of interest: the chronic fatigue syndrome, the sicca syndrome, the non-insulin-dependent diabetes mellitus, malignant B cell proliferations, mainly the Hepatis C Virus-related splenic lymphoma with villous lymphocytes and the production of auto-antibodies. PERSPECTIVES AND PROJECTS: The mechanisms underlying these HCV-associated EHM are ill-elucidated and still remain of great interest as proved by current studies. The use of anti-CD20 antibodies in the treatment of cryoglobulinemic vasculitis is also under investigation.
18515326 Endothelins modulate inflammatory reaction in zymosan-induced arthritis: participation of 2008 Sep Endothelins (ETs) are involved in inflammatory events, including pain, fever, edema, and cell migration. ET-1 levels are increased in plasma and synovial membrane of rheumatoid arthritis (RA) patients, but the evidence that ETs participate in RA physiopathology is limited. The present study investigated the involvement of ETs in neutrophil accumulation and edema formation in the murine model of zymosan-induced arthritis. Intra-articular (i.a.) administration of selective ET(A) or ET(B) receptor antagonists (BQ-123 and BQ-788, respectively; 15 pmol/cavity) prior to i.a. zymosan injection (500 microg/cavity) markedly reduced knee-joint edema formation and neutrophil influx to the synovial cavity 6 h and 24 h after stimulation. Histological analysis showed that ET(A) or ET(B) receptor blockade suppressed zymosan-induced neutrophil accumulation in articular tissue at 6 h. Likewise, dual blockade of ET(A)/ET(B) with bosentan (10 mg/kg, i.v.) also reduced edema formation and neutrophil counts 6 h after zymosan stimulation. Pretreatment with BQ-123 or BQ-788 (i.a.; 15 pmol/cavity) also decreased zymosan-induced TNF-alpha production within 6 h, keratinocyte-derived chemokine/CXCL1 production within 24 h, and leukotriene B(4) at both time-points. Consistent with the demonstration that ET receptor antagonists inhibit zymosan-induced inflammation, i.a. injection of ET-1 (1-30 pmol/cavity) or sarafotoxin S6c (0.1-30 pmol/cavity) also triggered edema formation and neutrophil accumulation within 6 h. Moreover, knee-joint synovial tissue expressed ET(A) and ET(B) receptors. These findings suggest that endogenous ETs contribute to knee-joint inflammation, acting through ET(A) and ET(B) receptors and modulating edema formation, neutrophil recruitment, and production of inflammatory mediators.
17380399 Cryoglobulinemia related to hepatitis C virus infection. 2007 Apr A causal link among hepatitis C virus (HCV) infection and essential mixed cryoglobulinemia, cryoglobulinemic glomerulonephritis, and vasculitis is strongly supported. HCV triggers autoimmune response in predisposed individuals that manifests as organ-specific and non-organ-specific autoantibodies and as polyclonal/monoclonal rheumatoid factor, which has a central role in causing damaging cryoglobulin and immune complex tissue levels. Immunologic events are mainly induced by HCV infection persistence, with excessive immune stimulation. Humoral immune dysfunction leads to autoantibodies and rheumatoid factor production with cryoglobulinemia, glomerulonephritis, vasculitis, neuropathy, and probably thyroiditis, and arthritis in rare cases. Cellular immune dysfunction leads to lymphocytic infiltration, proliferation, and cytokine production. Pegylated (or not) interferon-alpha in combination with ribavirin appears to be the treatment of choice for patients with symptomatic essential mixed cryoglobulinemia with or without glomerulonephritis. Novel treatment with rituximab is promising.
18691023 Perspectives on the use of gene therapy for chronic joint diseases. 2008 Aug Advances in molecular and cellular biology have identified a wide variety of proteins including targeted cytokine inhibitors, immunomodulatory proteins, cytotoxic mediators, angiogenesis inhibitors, and intracellular signalling molecules that could be of great benefit in the treatment of chronic joint diseases, such as osteo- and rheumatoid arthritis. Unfortunately, protein-based drugs are difficult to administer effectively. They have a high rate of turnover, requiring frequent readministration, and exposure in non-diseased tissue can lead to serious side effects. Gene transfer technologies offer methods to enhance the efficacy of protein-based therapies, enabling the body to produce these molecules locally at elevated levels for extended periods. The proof of concept of gene therapies for arthritis has been exhaustively demonstrated in multiple laboratories and in numerous animal models. This review attempts to condense these studies and to discuss the relative benefits and limitations of the methods proposed and to discuss the challenges toward translating these technologies into clinical realities.
18155297 Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. 2008 Feb During the past 30 years, elucidation of the pathogenesis of rheumatoid arthritis, Crohn's disease, psoriasis, psoriatic arthritis and ankylosing spondylitis at the cellular and molecular levels has revealed that these diseases share common mechanisms and are more closely related than was previously recognized. Research on the complex biology of tumor necrosis factor (TNF) has uncovered many mechanisms and pathways by which TNF may be involved in the pathogenesis of these diseases. There are 3 TNF antagonists currently available: adalimumab, a fully human monoclonal antibody; etanercept, a soluble receptor construct; and infliximab, a chimeric monoclonal antibody. Two other TNF antagonists, certolizumab and golimumab, are in clinical development. The remarkable efficacy of TNF antagonists in these diseases places TNF in the center of our understanding of the pathogenesis of many immune-mediated inflammatory diseases. The purpose of this review is to discuss the biology of TNF and related family members in the context of the potential mechanisms of action of TNF antagonists in a variety of immune-mediated inflammatory diseases. Possible mechanistic differences between TNF antagonists are addressed with regard to their efficacy and safety profiles.
17148471 Non-Hodgkin's lymphoma--meta-analyses of the effects of corticosteroids and non-steroidal 2007 Apr OBJECTIVE: Recent research has focused on the effects of corticosteroids and non-steroidal anti-inflammatory drugs/agents (NSAIDs) on non-Hodgkin's lymphoma (NHL) risk, with inconclusive results. We conducted meta-analyses of data published to date, to ascertain the over-all association between NHL and corticosteroid use, and between NHL and NSAID use. METHODS: Literature searches were performed to find studies assessing the effects of corticosteroids and/or NSAIDs on NHL risk. We analysed nine case-control studies and one cohort study of the effect of corticosteroids and/or NSAIDs on NHL risk. We performed a formal meta-analysis using summary measures from these studies. RESULTS: The studies contributed 6897 NHL cases and 8881 controls for the corticosteroid analyses, and 5794 NHL cases and 34,707 controls for the NSAID analyses. There was no heterogeneity of the odds ratio (OR) estimates. The overall OR for the effect of corticosteroid exposure on NHL occurrence was not suggestive of an increased risk [OR 1.09, 95% confidence interval (CI) 0.96-1.24]. Similarly, the OR for the effect of NSAIDs on NHL occurrence did not support an increased risk (OR 0.93, 95% CI 0.74-1.14). CONCLUSIONS: Our meta-analyses suggest little evidence that corticosteroid or NSAID exposures are themselves risk factors for NHL. Early data linking corticosteroids and/or NSAIDs with NHL may reflect an underlying increased risk of lymphoma in patient populations that use these medications (i.e. autoimmune diseases such as rheumatoid arthritis), and may point to the importance of disease activity in driving NHL risk in these populations.
18937726 A case report of plasma exchange, steroids, mycophenolate mofetil and cyclophosphamide in 2008 Oct Induction of factor VIII (FVIII) inhibitors sometimes occurs in patients with hemophilia due to frequent supplementation of FVIII. The inhibitor is rarely detected in non-hemophilic patients; however, an association has been described in patients with chronic inflammatory diseases, such as autoimmune diseases (e.g. SLE and rheumatoid arthritis), malignant tumors and drug allergies, and also to pregnant or aged individuals without underlying disease. We report on an 82-year-old patient who was transferred to our hospital after the diagnosis of acquired FVIII inhibitor. On admission the laboratory results showed no detectable FVIII activity (0%, normal range 70-100%), prolongation of coagulation time (APTT 102.4 s), and severe anemia 7.8 g/dL (normal range 12-16 g/dL). On physical examination multiple subcutaneous hematomas were detected and further bleeding in his left pectoralis muscle was observed. Despite extensive investigation no underlying disease was detected. Thirty-six courses of plasma exchange with 360 units of fresh frozen plasma replacement daily were conducted. High dose steroids and mycophenolate mofetil (MMF) were given throughout the course, and cyclophosphamide was administered once. Thirty-four units of erythrocytes were applied during this time. After 36 courses of plasma exchange in combination with high dose steroids, FVIII activity and coagulation time normalized and bleeding could be stopped. The patient was discharged in good health 48 days after admission. Hence, we present a case of severe idiopathic FVIII inhibitor-positive hemophilia successfully treated with the combination of plasma exchange, corticosteroids, cyclophosphamide and MMF.