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ID PMID Title PublicationDate abstract
23253433 B-cell targeted therapy with rituximab for thyroid eye disease: closer to the clinic. 2013 May The management of thyroid eye disease (TED) remains a therapeutic challenge. The current established therapies are unsatisfactory in one-third of the patients and have many limitations. Rituximab (RTX) is a CD20+ B-cell-depleting monoclonal antibody approved for the treatment of non-Hodgkin lymphomas, chronic lymphocytic leukemia, and rheumatoid arthritis. The early experience with RTX suggests that it is a promising alternative therapy for TED. Rituximab may compare favorably to the conventional glucocorticoid therapy and causes less collateral damage than retrobulbar orbital radiation and decompression surgery. In addition, the preliminary studies on RTX's proposed mechanism of action have revealed new insights into the pathogenic role of B-cells in TED. We summarize the current literature on the clinical application of RTX in TED and discuss its putative mechanisms of action.
22719769 IgG4-Related Lymphadenopathy. 2012 Lymphadenopathy is frequently observed in patients with immunoglobulin G4-related disease (IgG4-RD) and sometimes appears as the first manifestation of the disease. The diagnosis of IgG4-related lymphadenopathy is complicated owing to a great histological diversity, with at least 5 histological subtypes. Indeed, lymph node biopsy may be performed under the suspicion that the lymphadenopathy is a malignant lymphoma or other lymphoproliferative disorder. The diagnosis of IgG4-RD is characterized by both elevated serum IgG4 (>135 mg/dL) and histopathological features, including a dense lymphoplasmacytic infiltrate rich in IgG4(+) plasma cells (IgG4(+)/IgG(+) plasma cell ratio >40%). However, patients with hyper-interleukin (IL-) 6 syndromes such as multicentric Castleman's disease, rheumatoid arthritis, and other immune-mediated conditions frequently show lymph node involvement and often fulfill the diagnostic criteria for IgG4-RD. Owing to these factors, IgG4-RD cannot be differentiated from hyper-IL-6 syndromes on the basis of histological findings alone. Laboratory analyses are crucial to differentiate between the 2 diseases. Hyper-IL-6 syndromes are characterized by elevated serum levels of IgG, IgA, IgM, and C-reactive protein (CRP); thrombocytosis; anemia; hypoalbuminemia; hypocholesterolemia. In contrast, IgG4-RD does not share any of these characteristics. Therefore, the diagnosis of IgG4-RD requires not only pathological findings but also clinical and laboratory analyses.
22596111 Dysexecutive syndrome: a specific pattern of cognitive impairment in systemic sclerosis. 2012 Jun BACKGROUND AND PURPOSE: Systemic sclerosis (SSc) is a connective-tissue disorder characterized by microvascular damage and tissue fibrosis. Although overt nervous system involvement is unusual in SSc, imaging studies have shown cerebral hypoperfusion. We evaluated cognitive functions in patients with SSc who had no history of neurological involvement, to seek cognitive impairment caused by the suggested cerebral hypoperfusion. METHODS: We performed a comprehensive neuropsychological test battery on 31 patients with SSc and on 2 groups of age-adjusted, sex-adjusted, and education-adjusted controls: 15 patients with rheumatoid arthritis and 20 healthy volunteers. RESULTS: The patients with SSc scored significantly worse on most of the measures of executive function than the 2 control groups (P<0.05). However, both patient groups did worse than the healthy controls on measures of attention and memory (P<0.005). CONCLUSIONS: Our results suggest that patients with SSc have a specific pattern of cognitive impairment: the dysexecutive syndrome. Attentional and memory problems, however, may arise from other confounders such as disease duration and chronic medication use. SSc may be a rare cause of vascular cognitive impairment.
22593761 The Fyn-STAT5 Pathway: A New Frontier in IgE- and IgG-Mediated Mast Cell Signaling. 2012 Mast cells are central players in immune surveillance and activation, positioned at the host-environment interface. Understanding the signaling events controlling mast cell function, especially those that maintain host homeostasis, is an important and still less understood area of mast cell-mediated disease. With respect to allergic disease, it is well established that IgE and its high affinity receptor FcεRI are major mediators of mast cell activation. However, IgG-mediated signals can also modulate mast cell activities. Signals elicited by IgG binding to its cognate receptors (FcγR) are the basis for autoimmune disorders such as lupus and rheumatoid arthritis. Using knowledge of IgE-mediated mast cell signaling, recent work has begun to illuminate potential overlap between FcεRI and FcγR signal transduction. Herein we review the importance of Src family kinases in FcεRI and FcγR signaling, the role of the transcription factor STAT5, and impingement of the regulatory cytokines IL-4, IL-10, and TGFβ1 upon this network.
22493341 Multiple associations between a broad spectrum of autoimmune diseases, chronic inflammator 2012 Apr BACKGROUND: Many recent studies suggest the immune system plays a significant role in the pathogenesis of autoimmune diseases, chronic inflammatory diseases, and cancer. MATERIALS AND METHODS: Literature published between 2001 and 2011 was reviewed for risk of cancer development in patients with autoimmune and chronic inflammatory diseases. Mode of risk assessment employed did not limit inclusion of studies. Autoimmune conditions developing after diagnosis of a pre-existing cancer were also considered. RESULTS: We report a pervasive, largely positive association between 23 autoimmune and inflammatory diseases and subsequent cancer development. We discuss associations for celiac disease, inflammatory bowel disease rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis in detail. We also address the less frequently reported development of some autoimmune conditions within the course of some malignancies, such as vitiligo developing in the course of melanoma. CONCLUSION: Evidence demonstrates that chronic inflammation and autoimmunity are associated with the development of malignancy. Additionally, patients with a primary malignancy may develop autoimmune like disease. These relationships imply a need for surveillance of patients on immunomodulatory therapies for potential secondary disease processes.
22374440 [Usefulness of measuring serum IgG4 level as diagnostic and treatment marker in IgG4-relat 2012 IgG4-related disease is a chronic disorder, which is characterized with elevated levels of serum immunoglobulin (Ig)G4 and abundant infiltration of IgG4-positive plasmacyte and storiform fibrosis in the enlarged organs. It includes Mikulicz's disease (IgG4-related dacryoadenitis and sialadenitis), autoimmune pancreatitis type I, and so on. In Japan, we have been able to measure the IgG4 levels in our clinic since 2010, and we knew that various diseases except IgG4-related disease, also presented with elevated levels of serum IgG4. Eosinopihic disorders, such as Chrug-Strauss syndrome, a part of rheumatoid arthritis and systemic sclerosis can present with high levels of serum IgG4. So the confusion is seen in some clinicians, but we have to recognize that only serological findings cannot lead to the correct diagnosis in IgG4-related disease. The pathological and image findings also are needed. With regard of the treatments for IgG4-related disease, the levels of serum IgG4 often reflected with the therapeutic response, and were also the markers, which predicted the relapse. We describe herein the significance of measuring serum IgG4 levels in the diagnosis and during the treatment for IgG4-related disease.
26181879 Human intestinal spirochetosis in an immunocompromised host: evaluation of eradication the 2012 Feb Human intestinal spirochetosis (HIS) is a colorectal infectious disease caused by Brachyspira species. We describe HIS in an immunocompromised, 62-year-old Japanese man who presented at Jichi Medical University Hospital with symptoms of diarrhea and bloody stool. He had rheumatoid arthritis that had been treated with immunosuppressive drugs for 10 years. Colonoscopy revealed multiple erythematous spots in the cecum and colon. A histopathological examination identified intestinal colonization by spirochetes, and Brachyspira pilosicoli was isolated from biopsy specimens, indicating a diagnosis of HIS. Metronidazole eradicated the spirochetes, the intestinal mucosa recovered to normal, and the clinical symptoms disappeared. This case suggests that it is important to keep in mind HIS in the differential diagnosis of immunocompromised patients with chronic diarrhea and bloody stool.
22225601 Sex affects immunity. 2012 May Sex based differences in immune responses, affecting both the innate and adaptive immune responses, contribute to differences in the pathogenesis of infectious diseases in males and females, the response to viral vaccines and the prevalence of autoimmune diseases. Indeed, females have a lower burden of bacterial, viral and parasitic infections, most evident during their reproductive years. Conversely, females have a higher prevalence of a number of autoimmune diseases, including Sjogren's syndrome, systemic lupus erythematosus (SLE), scleroderma, rheumatoid arthritis (RA) and multiple sclerosis (MS). These observations suggest that gonadal hormones may have a role in this sex differential. The fundamental differences in the immune systems of males and females are attributed not only to differences in sex hormones, but are related to X chromosome gene contributions and the effects of environmental factors. A comprehensive understanding of the role that sex plays in the immune response is required for therapeutic intervention strategies against infections and the development of appropriate and effective therapies for autoimmune diseases for both males and females. This review will focus on the differences between male and female immune responses in terms of innate and adaptive immunity, and the effects of sex hormones in SLE, MS and RA.
21978567 Extensor mechanism repair failure with use of bidirectional barbed suture in total knee ar 2012 Aug Total knee arthroplasty (TKA) continues to advance as innovative devices become available. #2 PDO Quill SRS (Angiotech, Reading, Pa) bidirectional barbed suture was used for 161 primary TKAs at our facility. We report on 3 separate cases of extensor mechanism repair failure after primary TKA in which a barbed suture was used for extensor mechanism closure. Before the implementation of this device, there were no reported failures in 385 primary TKAs. We recommend that surgeons who use this device for extensor mechanism repair of a medial parapatellar arthrotomy in TKA exercise caution when operating on patients with morbid obesity, diabetes, and rheumatoid arthritis. We have discontinued use of the bidirectional barbed suture until more definitive large orthopedic studies establish its efficacy and safety.
21899684 Immune reconstitution inflammatory syndrome manifesting as development of multiple autoimm 2011 Sep We report the case of a 56-year-old man with the rare autoimmune pathologies of alternating hypothyroidism and hyperthyroidism due to thyroid-stimulating hormone receptor antibodies, and rheumatoid arthritis as manifestations of a human immunodeficiency virus-related immune reconstitution inflammatory syndrome. The patient also developed overt progression of a pre-existing skin malignancy that may also be related. This case highlights immune reconstitution syndrome as an important differential diagnosis following antiretroviral therapy commencement, and that a high index of suspicion should be maintained for this rare but important cluster of conditions. Furthermore, the patient's genetic predisposition to autoimmunity provides helpful insights into the pathogenesis of these disorders.
21881286 Etanercept-induced lupus accompanied by hemophagocytic syndrome. 2011 Hemophagocytic syndrome (HPS) is a severe, potentially life-threatening disorder characterized by an excessive activation of macrophages, such as may occur in the setting of lupus. A 62-year-old Japanese woman treated with etanercept for rheumatoid arthritis developed persistent fever, cytopenia, coagulopathy, and hyperferritinemia. Simultaneously, lupus-like features including pleuritis, hypocomplementemia, and positive autoantibodies were observed. She was diagnosed with HPS related to etanercept-induced lupus, and underwent immunosuppressive therapy with successful recovery. To our knowledge, this is the first case of etanercept-induced lupus accompanied by HPS. This case suggests that HPS should be considered as a complication during TNF-α inhibitor therapy.
21839315 Vitiligo: a comprehensive overview Part I. Introduction, epidemiology, quality of life, di 2011 Sep Vitiligo is an acquired pigmentary disorder of unknown etiology that is clinically characterized by the development of white macules related to the selective loss of melanocytes. The prevalence of the disease is around 1% in the United States and in Europe, but ranges from less than 0.1% to greater than 8% worldwide. A recorded predominance of women may reflect their greater willingness to express concern about cosmetically relevant issues. Half of all patients develop the disease before 20 years of age. Onset at an advanced age occurs but is unusual, and should raise concerns about associated diseases, such as thyroid dysfunction, rheumatoid arthritis, diabetes mellitus, and alopecia areata. Generalized vitiligo is the most common clinical presentation and often involves the face and acral regions. The course of the disease is unpredictable and the response to treatment varies. Depigmentation may be the source of severe psychological distress, diminished quality of life, and increased risk of psychiatric morbidity. Part I of this two-part series describes the clinical presentation, histopathologic findings, and various hypotheses for the pathogenesis of vitiligo based on past and current research.
21809045 Evaluation of lasting high levels of CRP among the patients with metabolic syndrome. 2012 Apr "Low-grade" systemic inflammation is common findings in patients with metabolic syndrome (MetS). When we assessed 256 MetS patients, we found eight patients who presented high levels of C-reactive protein (CRP) which are between 40 and 15 mg/L for more than 3 years. They have not satisfied any criteria of inflammatory diseases such as rheumatoid arthritis and the area of visceral fat estimated by computed tomography was more than 200 cm(2). All the other MetS patients of visceral fat over 200 cm(2) presented low levels of CRP which are less than 10 mg/L. Insulin resistance and ultrasound study of carotid plaques showed no differences between high and low levels of CRP patients. There are a series of MetS patients who show high levels of CRP without clinical symptoms of inflammatory diseases. High levels of CRP merely cannot be explained by visceral fat area, insulin resistance, or carotid plaques.
21768240 Mammographic signs of systemic disease. 2011 Jul Although mammography is primarily used for the detection of breast cancer, it can occasionally reveal breast abnormalities related to extramammary disease. Cardiovascular diseases such as congestive heart failure and central venous obstruction may manifest as venous engorgement and breast edema at mammography. Pathologic arterial calcifications seen at mammography can indicate an underlying risk factor for accelerated atherosclerosis such as chronic renal failure. Connective tissue diseases including rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis-polymyositis, and systemic scleroderma typically manifest with bilateral axillary lymphadenopathy, and stromal calcifications are also seen in the latter three disease processes. Some diseases such as neurofibromatosis type 1 and filariasis may manifest with pathognomonic findings at mammography, whereas other systemic diseases such as Wegener granulomatosis, sarcoidosis, and amyloidosis can manifest as nonspecific breast masses that are indistinguishable from breast cancer and usually require tissue biopsy for confirmation. Knowledge of the imaging characteristics of various systemic diseases affecting the breast will aid the radiologist in differentiating systemic disease from suspect breast lesions, thereby helping ensure appropriate follow-up. Furthermore, recognition of systemic diseases such as Cowden syndrome that are associated with an increased risk of breast cancer will allow the radiologist to recommend appropriate surveillance.
21720596 Challenges and solutions for total hip arthroplasty in treatment of patients with symptoma 2011 Feb Conditions that adversely affect a child's hip alignment, joint congruity, or articular surfaces often result in joint destruction associated with pain and motion limitation later in life. The usual culprits are developmental dysplasia of the hip (DDH), slipped capital femoral epiphysis, Legg-Calvé-Perthes disease, juvenile rheumatoid arthritis, infection, trauma, and neoplasm. In this review, we address DDH, the most common cause of secondary osteoarthritis of the hip. Symptomatic sequelae of DDH present challenges for total hip arthroplasty, including excessive proximal femoral anteversion, narrowing of the medullary canal, acetabular anteversion, verticality, hypoplasia and incongruity, pseudoacetabulum, and neurovascular shortening. Presiding corrective femoral and/or acetabular osteotomies, as well as retained hardware, further complicate total hip arthroplasty. This review emphasizes evaluation of hip morphology while considering reconstructive techniques and implants.
21548528 Electron spin resonance. Part one: a diagnostic method in the biomedical sciences. 2011 A review is presented of some of the ways in which electron spin resonance (ESR) spectroscopy may be useful to investigate systems of relevance to the biomedical sciences. Specifically considered are: spin-trapping in biological media; the determination of antioxidant efficiencies; lipid-peroxidation; the use of nitroxides as probes of metabolic activity in cells and as structumral probes of cell-membranes; ESR coupled with materials for radiation-dosimetry; food- and drug-irradiation; studies of enzyme systems and ofcyclodextrins; diagnosis of cancer and rheumatoid arthritis; measurement of oxidative stress in synovial tissue in preparation for joint replacement; determination of oxidative species during kidney dialysis; measurement of biological oxygen concentrations (oximetry); trapping in living cells of the endothelium-derived relaxing factor nitric oxide (NO); measurement of hydrogen peroxide; determination of drugs of abuse (opiates); ESR measurements of whole blood and as a means to determine the age of bloodstains for forensic analysis are surveyed, and also a determination of the aqueous volume of human sperm cells is described, among other topics.
21358309 Structural bone changes in spondyloarthritis: mechanisms, clinical impact and therapeutic 2011 Apr Spondyloarthritis (SpA) is an inflammatory disease of the spine, the peripheral joints and the entheses and shares some clinical features with rheumatoid arthritis (RA). Chronic inflammation of musculoskeletal structures leads to disease symptoms such as pain and stiffness and structural changes in the bone tissue. Furthermore, therapies for SpA are based on those for RA, which attempt to inhibit synovial inflammation that leads to retardation or even arrest of structural damage. However, in SpA, the bone tissue directly exposed to inflammation (osteitis) is the trabecular bone of the vertebrae, but not the cortical bone surface as in RA (synovitis). Therefore, the success of treatment strategies for structural changes in RA may not be appropriate for SpA. In this article, the authors discuss the pathophysiology of structural damage in SpA and concepts for the preservation of the physiologic bone architecture in patients with SpA.
21327472 Techniques of assessing hypoxia at the bench and bedside. 2011 May Tissues require an adequate supply of oxygen in order to maintain normal cell function. Low oxygen tension (hypoxia) is characteristic of a number of conditions, including cancer, atherosclerosis, rheumatoid arthritis, critical limb ischaemia, peripheral vascular disease, and ischaemic heart disease. Tissue hypoxia is found in tumours, atherosclerotic plaque, and ischaemic myocardium. There is a growing interest in methods to detect and assess hypoxia, given that hypoxia is important in the progression of these diseases. Hypoxia can be assessed at the level of the whole organ, tissue, or cell, using both invasive and non-invasive methods, and by a range of immunohistochemical, biochemical, or imaging techniques. This review describes and critiques current methods of assessing hypoxia that are used at the bench and in clinical practice.
24312757 Hollow microspheres for gastroretentive floating- pulsatile drug delivery: preparation and 2011 PURPOSE: A multiparticular floating-pulsatile drug delivery system was developed for time and site specific drug release of piroxicam. A blend of floating and pulsatile principles of drug delivery system would have the advantage that a drug can be released in the upper GI tract after a definite time period. METHODS: Hollow microspheres were prepared by the emulsion solvent diffusion method using Eudragit S as an enteric acrylic polymer with piroxicam at various polymer/drug ratios in a mixture of dichloromethane and ethanol. Developed formulations were evaluated for yield, encapsulation efficiency, particle size, shape, apparent density, buoyancy studies and dissolution studies. RESULTS: The obtained microballoons were spherical with no major surface irregularity and mean particle size ranging from 250 to 380 for different batches. Formulations show a slight amount of relaese ranging from 0.7 to 11% in acidic medium (SGF) with complete release of drug in simulated intestinal fluid (SIF) in less than 3 h. Encapsulation efficiency of different formulations varied from 90 to 98%. The optimum loading amount of drug in the particles was found to impart suitable floatable properties to the microballoons. With increasing polymer/drug ratio, buancy of the microballoons increases accompanied by simultaneous reduction of apparent particle density. CONCLUSION: A pulsatile release of piroxicam was demonstrated by a simple drug delivery system which could be useful in chronopharmacotherapy of rheumatoid arthritis.
21117080 A new regulatory switch in a JAK protein kinase. 2011 Feb Members of the JAK family of protein kinases mediate signal transduction from cytokine receptors to transcription factor activation. Over-stimulation of these pathways is causative in immune disorders like rheumatoid arthritis, psoriasis, lupus, and Crohn's disease. A search for selective inhibitors of a JAK kinase has led to our characterization of a previously unknown kinase conformation arising from presentation of Tyr962 of TYK2 to an inhibitory small molecule via an H-bonding interaction. A small minority of protein kinase domains has a Tyrosine residue in this position within the αC-β4 loop, and it is the only amino acid commonly seen here with H-bonding potential. These discoveries will aid design of inhibitors that discriminate among the JAK family and more widely among protein kinases.