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ID PMID Title PublicationDate abstract
20970225 [Azathioprine-associated severe myelosuppression: indication of routine determination of t 2011 Jun INTRODUCTION: Myelotoxicity is a well-known adverse effect of azathioprine, leading mainly to leukopenia. Other azathioprine associated hematological adverse effects are uncommon. CASE REPORT: We report a 49-year-old woman with rheumatoid arthritis and acquired hemophilia, who presented a severe myelosuppression occurring 3 weeks after an increase of her azathioprine regimen (at a daily dose of 150 mg). The patient had a heterozygous mutation of the thiopurine S-methyltransferase gene (TPMT*3A). Azathioprine therapy was discontinued and she recovered at 3 weeks. The patient had no relapse of pancytopenia after a 1 year follow-up. CONCLUSION: Routine measurement of TPMT activity or determination of TPMT variant allele may be useful tests, in order to identify the subgroup of patients who are at risk to develop azathioprine induced severe myelosuppression.
22527726 Pathways for bone loss in inflammatory disease. 2012 Jun Chronic inflammation including autoimmune disease is an important risk factor for the development of osteoporosis. Receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) play a central role in osteoclast differentiation and function, and the molecular pathways by which M-CSF and RANKL induce osteoclast differentiation have been analyzed in detail. Proinflammatory cytokines directly or indirectly regulate osteoclastogenesis and bone resorption providing a link between inflammation and osteoporosis. Tumor necrosis factor-α, interleukin (IL)-1, IL-6, and IL-17 are the most important proinflammatory cytokines triggering inflammatory bone loss. Inhibition of these cytokines has provided potent therapeutic effects in the treatment of diseases such as rheumatoid arthritis. Further investigation is needed to understand the pathophysiology and to develop new strategies to treat inflammatory bone loss. This review summarizes new data on inflammatory bone loss obtained in 2011.
23363021 Possible antistenotic effect of tranilast in a patient with small bowel tuberculosis to pr 2013 May Small intestinal tuberculosis is a rare disorder of the small intestine. We report the development of deep small bowel tuberculosis in a rheumatoid arthritis patient who was taking methotrexate. The diagnosis of small bowel tuberculosis was ascertained by typical endoscopic findings and production of interferon gamma in the peripheral blood. The patient was successfully treated with antituberculous chemotherapy combined with an antifibrotic agent, tranilast, to suppress the progression of intestinal stenosis toward symptomatic stricture.
23229531 [Bone ultrasonography in kidney disease: applications and limitations]. 2012 Nov Quantitative ultrasound (QUS) of the bone is a technique that is generating great interest among bone structure researchers because of its intrinsic features. Its safety and low cost make it an ideal technique for repeated measurements over time such as in chronic disease or when it is necessary to monitor the effects of prescribed therapies. The method was developed for the study of osteoporosis and the sites of measurement are all peripheral, including the distal diaphyses and metaphyses of the phalanges, calcaneus, radius and tibia. QUS parameters, however, cannot be used directly for the diagnosis of osteoporosis according to the WHO criteria, although many authors have shown that ultrasound parameters, particularly those of calcaneal QUS, can predict the risk of osteoporotic fractures independently of MBD. Very promising results with the use of QUS have been obtained in corticosteroid-induced osteoporosis, rheumatoid arthritis, Cushing's syndrome, cystic fibrosis, osteomalacia, thalassemia and osteopenia related to parenteral nutrition. QUS can also monitor the effectiveness of therapy in various pathological conditions. In nephrology the combined use of phalangeal QUS and biochemical markers of bone turnover allows adequate follow-up of patients on dialysis and renal transplant recipients with alterations or disorders of the bone.
22956390 An update on stem cell transplantation in autoimmune rheumatologic disorders. 2012 Dec Stem cell transplant (SCT) has long been the standard of care for several hematologic, immunodeficient, and oncologic disorders. Recently, SCT has become an increasingly utilized therapy for refractory autoimmune rheumatologic disorders (ARDs). The efficacy of SCT in ARDs has been attributed to resetting an aberrant immune system either through direct immune replacement with hematopoietic stem cells or through immunomodulation with mesenchymal stem cells. Among ARDs, refractory systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are the most common indications for SCT. SCT has also been used in refractory rheumatoid arthritis, inflammatory myopathies, antiphospholipid syndrome, granulomatosis with polyangiitis, and pediatric ARDs. Complete responses have been reported in approximately 30 % of patients in all disease categories. Transplant-related mortality, however, remains a concern. Future large multi-center prospective randomized clinical trials will help to better define the specific role of SCT in the treatment of patients with ARDs.
22934744 Analysis of anti-inflammatory enantiomers by HPLC in human plasma and urine: a review. 2012 The analysis of drugs in various biological fluids is an important criterion for the determination of the physiological performance of a drug. NSAIDs are non-selective inhibitors of prostaglandin biosynthesis and indicated for the acute or long-term treatment of the signs and symptoms of rheumatoid arthritis and osteoarthritis. This paper reviews the recent developments in bioanalysis of these drugs. In particular, sample preparation end, handling procedures, chromatographic conditions and detection methods are discussed. A summary of published HPLC assays for individual antiinflammatory drugs is included.
22856418 [Psoriasis induced by infliximab]. 2011 Dec INTRODUCTION: Recently, the tumor necrosis factor-α inhibitors (anti-TNF-α) have been extensively used in clinical practice, in the treatment of several immune-mediated disorders, such as inflammatory bowel diseases, rheumatoid arthritis and more recently in psoriasis. CASE REPORT: A 35-year-old woman, suffering from Crohn's disease, diagnosed in 1994, successfully treated with infliximab at the dosage of 5 mg/Kg every 8 weeks, since 10 months ago, was referred to our Dermatology Department due to the development of erythematic-scaling confluent plaques on the scalp, back and umbilical fold. The skin biopsy confirmed the clinical diagnosis of psoriasis. Given the severity of the skin lesions and its relation with the anti-TNF-α, we decided to discontinue infliximab. DISCUSSION: Psoriasis results from the combination of polygenic predisposition and several triggering factors. Paradoxically, it has been described an increase of psoriasis induced by biologic agents. The pathogenic mechanism of such paradoxical effect has not yet been clearly elucidated.
22776785 Exercise as a therapeutic tool to counteract inflammation and clinical symptoms in autoimm 2012 Dec Chronic inflammation is a common feature shared by several autoimmune rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, idiopathic inflammatory myopathies, systemic sclerosis, and ankylosing spondylitis. Therefore, blocking or reducing inflammation is one of the major treatment strategies in these diseases. In this context, exercise training has emerged as a potential therapeutic tool in counteracting systemic inflammation, thereby leading to better clinical outcomes. The aims of this review are i) to provide a summary of the clinical effects of exercise training in selected autoimmune rheumatic diseases; and ii) to discuss the potential anti-inflammatory role of exercise training in autoimmune rheumatic diseases, stressing the gaps in literature and the clinical and scientific perspectives in the field.
22222237 Sex gender and autoimmunity. 2012 May The 7th International Congress of Autoimmunity was held in Ljubljana, Slovenia in May 2010. At the conclusion of the Congress, a list was prepared of the major unresolved clinical issues in autoimmunity. The list grew to be extensive but one subject that was found in nearly all of the concerns was geoepidemiology of autoimmunity and, in particular, the increased risk of women to develop autoimmune disease. Indeed, one does not need to be an autoimmunologist to appreciate that the risk of developing rheumatoid arthritis, for example, has been known to be increased in women compared to men, almost from the time of its original description. In fact, although the sex ratios of autoimmune disease have varied from center to center, from country to country, from decade to decade, the data has remained virtually constant. It is not surprising that the very first mouse model of lupus was described in female New Zealand black x white female mice. Although there have been subsequent descriptions of lupus in male murine strains, the initial data on the NZB × NZW F1 mouse led to some of the original descriptions of the relative roles of sex hormones on the immune response. The 8th Congress of Autoimmunity will be held in Granada, Spain in May 2012 and one of the intents of the Congress and of this volume is to address the needs originally noted in Slovenia two years earlier. Towards this extent, this volume contains a special double issue of papers that will be published in the Journal of Autoimmunity and Autoimmunity Reviews, all of whom have the focus of addressing critical issues in sex, gender and autoimmunity.
22125107 [Chromogranin A (CgA) - the influence of various factors in vivo and in vitro, and existin 2011 Chromogranin A (CgA) is regarded as a major, nonspecific neuroendocrine tumour (NET) marker. The results of CgA blood concentration, however, may actually be influenced by various factors or coexisting pathological conditions. Among the factors causing a substantial increase of the blood CgA concentration are: treatment with proton-pump inhibitors or H2 -receptor blockers, chronic atrophic gastritis (type A), impaired renal function, prostate cancer and BPH, and rheumatoid arthritis with high level of RF IgM. In addition, the sort of investigated biological material (whether it is serum or plasma) is of importance. There are also many conditions which may have a moderate or little influence on the concentration of CgA, among them are: inflammatory bowel disease (ulcerative colitis and Crohn's disease), deteriorating liver function, untreated essential hypertension, heart failure, hypercortisolism, pregnancy, and, in some subjects, ingestion of a meal. Proper assessment of the CgA results requires detailed knowledge about various factors, drugs, and pathological conditions influencing its concentration in blood.
22198431 Fetal outcome in autoimmune diseases. 2012 May The impact on fetal outcome in women with autoimmune diseases is a result of a several conditions. Fetal success depends on early immunological changes in the mother, which rely in modifications of the innate and adaptative immune system, inducing tolerance to the semi-allogenic fetus. Others crucial factors are maternal disease activity, severity of organ damage, circulating antibodies, and drug treatment. Although fetal outcome is becoming better still it has a worse prognosis in comparison with healthy women. Diseases like antiphospholipid syndrome, systemic lupus erythematosus and vasculitis have the higher risk while rheumatoid arthritis and spondiloarthopaties the least. In the majority of the diseases the risk of poor fetal outcome directly correlates with the activity of disease. While there are no pathognomonic autoantibodies for fetal outcome, antiphospholipid and anti-thyroid antibodies have been implicated in unsuccessful pregnancies and anti-Ro and, to a lesser extent, anti-La antibodies may result in neonatal lupus syndrome congenital heart block. There is increasingly the hope that fetal outcome will be good if the disease is well controlled prior to pregnancy, and with a specialized interdisciplinary support.
22164144 Transforming Growth Factor-β and Endoglin Signaling Orchestrate Wound Healing. 2011 Physiological wound healing is a complex process requiring the temporal and spatial co-ordination of various signaling networks, biomechanical forces, and biochemical signaling pathways in both hypoxic and non-hypoxic conditions. Although a plethora of factors are required for successful physiological tissue repair, transforming growth factor beta (TGF-β) expression has been demonstrated throughout wound healing and shown to regulate many processes involved in tissue repair, including production of ECM, proteases, protease inhibitors, migration, chemotaxis, and proliferation of macrophages, fibroblasts of the granulation tissue, epithelial and capillary endothelial cells. TGF-β mediates these effects by stimulating signaling pathways through a receptor complex which contains Endoglin. Endoglin is expressed in a broad spectrum of proliferating and stem cells with elevated expression during hypoxia, and regulates important cellular functions such as proliferation and adhesion via Smad signaling. This review focuses on how the TGF-β family and Endoglin, regulate stem cell availability, and modulate cellular behavior within the wound microenvironment, includes current knowledge of the signaling pathways involved, and explores how this information may be applicable to inflammatory and/or angiogenic diseases such as fibrosis, rheumatoid arthritis and metastatic cancer.
22155203 Prolactin and autoimmunity. 2012 May Sex hormones, especially estrogen and prolactin (PRL), have an important role in modulating the immune response. PRL is secreted from the pituitary gland as well as other organs and cells particularly lymphocytes. PRL has an immune stimulatory effect and promotes autoimmunity. PRL interferes specifically with B cell tolerance induction, enhances proliferative response to antigens and mitogens and increases the production of immune globulins, cytokines and autoantibodies. Hyperprolactinemia (HPRL) in women present with clinical manifestations of galactorrhea, primary or secondary amenorrhea, delayed menarche or a change in the menses either in the amount or in the regularity. Furthermore in the last 2 decades multi-organ and organ specific autoimmune diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's syndrome (SS), Hashimoto's thyroiditis (HT), multiple sclerosis (MS), psoriasis, hepatitis C patients, Behçet's disease, peripartum cardiomyopathy (PPCM) and active celiac disease were discussed to be associated with HPRL. There is data showing correlation between PRL level and diseases activity in few diseases. Genetic factors may have a role in humans as in animal models. The PRL isoforms based on the differences in the amino acid sequence and size of the cytoplasmic domain have an important effect on the bioactivity on prolactin receptors (PRL-Rs).
21976261 [DGRW-update: patient education]. 2011 Oct Patient education programmes, i. e. standardized, manualized, interactive group programmes aiming to increase self-management and empowerment, are a core element of medical rehabilitation for chronic conditions. In an update of the evidence of the effectiveness of patient education, its effectiveness was proven for a broad spectrum of chronic disorders, such as diabetes mellitus, chronic low back pain, rheumatoid arthritis, coronary heart disease, chronic heart failure, bronchial asthma, COPD, and cancer, as well as for the modification of health behaviours, such as diet and exercise. To sustain effects, aftercare interventions, such as support provided by phone, were found to be successful. Interventions targeted to particular patient groups according to gender, age, or migration background are also being developed more frequently. When evaluating educational interventions not only distal outcomes, such as quality of life and participation, should be used but also proximal outcomes such as self-management skills. A recent survey of patient education practice in medical rehabilitation revealed a continuing potential for optimization relative to manualization, evaluation and didactics. However, the dissemination of innovative programmes into rehabilitation routine presents a major challenge.
21704094 Complement in health and disease. 2011 Sep 16 The complement system consists of about 35-40 proteins and glycoproteins present in blood plasma or on cell surfaces. Its main biological function is to recognise "foreign" particles and macromolecules, and to promote their elimination either by opsonisation or lysis. Although historically complement has been studied as a system for immune defence against bacteria, it has an important homeostatic role in which it recognises damaged or altered "self" components. Thus complement has major roles in both immune defence against microorganisms, and in clearance of damaged or "used" host components. Since complement proteins opsonise or lyse cells, complement can damage healthy host cells and tissues. The system is regulated by many endogenous regulatory proteins. Regulation is sometimes imperfect and both too much and too little complement activation is associated with many diseases. Excessive or inappropriate activation can cause tissue damage in diseases such as rheumatoid arthritis, age-related macular degeneration (AMD), multiple sclerosis, ischemia-reperfusion injury (e.g. ischemic stroke). Insufficient complement activity is associated with susceptibility to infection (mainly bacterial) and development of autoimmune disease, like SLE (systemic lupus erythematosus).
21814025 [Regulation of central tolerance by RANKL signaling]. 2011 Aug RANKL (receptor activator of NF-κB ligand) is a member of TNF (tumor-necrosis factor) family cytokine. Several genetic studies indicated critical roles of RANKL and its receptor RANK in bone homeostasis. RANKL-RANK signal regulates differentiation, survival and activation of osteoclasts. Therefore, suppression of the RANKL signal would be a promising strategy for interventions in osteoporosis or rheumatoid arthritis. Indeed, humanized anti-RANKL neutralizing antibody is coming onto the market as an antiresorptive agent for osteoporosis treatment. In addition to the role on bone homeostasis, several studies suggested that the RANKL-RANK interaction regulates immune response and development. For instance, RANKL was previously identified as a survival factor for dendritic cells. Moreover, we and other groups reported that the RANKL signal contributes to development of medullary thymic epithelial cells (mTECs) . mTECs ectopically express and present a number of tissue restricted antigens (e.g. insulin) of which expressions are in part regulated by autoimmune regulator (Aire) , a factor responsible for a genetic human autoimmune disorder, thereby eliminating T cells reactive to these tissue restricted self-antigens. As result, RANKL is involved in establishment of self-tolerance in thymus by regulating the development of mTECs expressing Aire and tissue restricted antigens.
21622648 Quantitative immunofluorescence mapping reveals little functional coclustering of proteins 2011 Aug 4 Platelets are small anucleate blood cells that aggregate to seal leaks at sites of vascular injury and are important in the pathology of atherosclerosis, acute coronary syndromes, rheumatoid arthritis, cancer, and the regulation of angiogenesis. In all cases, platelet aggregation requires release of stored proteins from α-granules. However, how proteins with potentially antagonistic functions are packaged within α-granules is controversial. One possibility is the packaging of functional agonists and antagonists into different α-granule populations. By quantitative immunofluorescence colocalization, we found that pair-wise comparisons of 15 angiogenic-relevant α-granule proteins displayed little, if any, pattern of functional coclustering. Rather, the data suggested a Gaussian distribution indicative of stochastic protein delivery to individual granules. The apparent physiologic paradox raised by these data may be explained through alternate mechanisms, such as differential content release through incomplete granule fusion or dampened and balanced regulatory networks brought about by the corelease of antagonistic factors.
21415192 Thoracic findings of systemic diseases at high-resolution CT in children. 2011 Mar Pulmonary involvement in systemic diseases is common, but the radiographic appearance of early-stage pulmonary changes is often subtle. Computed tomography (CT) has higher sensitivity and specificity than radiography, and high-resolution CT is the method of choice for accurate assessment of diffuse parenchymal lung disease. Even with reductions in the peak voltage and tube charge to minimize the exposure of pediatric patients to radiation, CT performed with a meticulous acquisition technique can provide detailed information. In some cases, high-resolution CT may depict clinically silent lung lesions. The information provided by CT is invaluable for planning therapy in pediatric patients with pulmonary involvement in connective tissue disease (eg, juvenile rheumatoid arthritis, dermatomyositis, systemic sclerosis, systemic lupus erythematosus, or mixed connective tissue disease), vasculitis, a primary or acquired immune deficiency disorder, immotile cilia syndrome, cystic fibrosis, or Langerhans cell histiocytosis.
20492077 Intralymphatic histiocytosis following placement of a metal implant. 2011 Apr Intralymphatic histiocytosis (IH) is a rare condition first reported in 1994 by O'Grady et al. Less than 40 cases have been reported, with the majority occurring in patients with rheumatoid arthritis. We present a case of a 72-year-old man who developed an asymptomatic rash on his left upper arm 3 years after placement of a metal implant to stabilize a fractured humerus. Examinations revealed a poorly demarcated erythematous to brown indurated plaque with a pebbly surface overlying the inferior portion of the surgical scar. Biopsy revealed a mixed dermal infiltrate with a complex glomeruloid intravascular accumulation of histiocytes and neutrophils. Histiocytes were identified with immunostaining for CD68. Immunostains for CD31 and D2-40 confirmed the intravascular location of the histiocytes. This reactive process is closely related to reactive angioendotheliomatosis, but is best classified as IH. This is the only case of IH reported in association with a metal implant of the upper arm and the fourth case reported in association with a metal implant. Although the pathogenesis of IH is unknown, a role for lymphatic stasis secondary to chronic inflammation or surgery has been suggested. This is a benign process with a chronic course, and there are no known efficacious treatments.
23320160 Can social history variables predict prison inmates' risk for latent tuberculosis infectio 2012 Improved screening and treatment of latent tuberculosis infection (LTBI) in correctional facilities may improve TB control. The Ohio Department of Rehabilitation and Correction (ODRC) consists of 32 prisons. Inmates are screened upon entry to ODRC and yearly thereafter. The objective of the study was to determine if social history factors such as tobacco, alcohol, and drug use are significant predictors of LTBI and treatment outcomes. We reviewed the medical charts of inmates and randomly selected age-matched controls at one ODRC facility for 2009. We used a conditional logistic regression to assess associations between selected social history variables and LTBI diagnosis. Eighty-nine inmates with a history of LTBI and 88 controls were identified. No social history variable was a significant predictor of LTBI. Medical comorbidities such as asthma, rheumatoid arthritis, and hepatitis C were significantly higher in inmates with LTBI. 84% of inmates diagnosed with LTBI had either completed or were on treatment. Annual TB screening may not be cost-effective in all inmate populations. Identification of factors to help target screening populations at risk for TB is critical. Social history variables did not predict LTBI in our inmate population. Additional studies are needed to identify inmates for the targeted TB testing.