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ID PMID Title PublicationDate abstract
20477139 Update on the use of biologics in primary systemic vasculitides. 2007 Nov The introduction of biologic therapies, which selectively target components of the immune system, has revolutionized the treatment of rheumatoid arthritis. Anti-TNF-alpha therapy (infliximab, etanercept and adalimumab) and B-cell-depleting agents, such as rituximab, are the most widely used agents. Increased experience of the use of biologic drugs in other immune-mediated inflammatory diseases has led to the application of biologic therapies in the treatment of primary systemic vasculitis. Conversely, the success of biological agents has improved understanding of the immunopathogenesis of vascular inflammation. The need for biologic agents arises from the failure of the current standard of care to maintain remission while limiting drug toxicity. Evidence for the efficacy of biologic agents does not match that of conventional immunosuppressants yet, but it is building rapidly. This paper reviews the current evidence for the standard of care of patients with vasculitis and the role of biologic therapy in primary systemic vasculitis. In this review, we examine the rationale for using biologics based on the pathophysiology of primary systemic vasculitis. The risks and benefits of the use of biologics are discussed, together with future directions and predictions of these emerging therapies.
17824176 Preclinical characterization of selective estrogen receptor beta agonists: new insights in 2006 It has now been over 10 years since Jan-Ake Gustafsson revealed the existence of a second form of the estrogen receptor (ERbeta) at a 1996 Keystone Symposium. Since then, substantial success has been made in distinguishing its potential biological functions from the previously known form (now called ERalpha) and how it might be exploited as a drug target. Subtype selective agonists have been particularly useful in this regard and suggest that ERbeta agonists may be useful for a variety of clinical applications without triggering classic estrogenic side effects such as uterine stimulation. These applications include inflammatory bowel disease, rheumatoid arthritis, endometriosis, and sepsis. This manuscript will summarize illustrative data for three ERbeta selective agonists, ERB-041, WAY-202196, and WAY-200070.
17709665 Combination immunosuppressive therapies: the promise and the peril. 2007 Aug BACKGROUND: Targeted immunotherapeutic agents (TIs), also known as biological agents, are efficacious treatments for many immunologically mediated disorders, including psoriasis. In several of these diseases, including rheumatoid arthritis, Crohn's disease, and multiple sclerosis, certain TIs have been studied in combination with nonspecific immunosuppressive agents and with other TIs. OBSERVATIONS: Recently, the rheumatology, neurology, and gastroenterology literature has reported several examples of possible associated toxic effects when certain TIs are used in combination with other immunosuppressive agents. These toxic effects have included an increased risk of infection and malignancy. CONCLUSIONS: Combination therapies are often used by dermatologists. Several TIs have been approved for psoriasis; however, clinical trials using these drugs in combination with other immunosuppressive agents have not yet been performed. The implications for dermatologists of the toxic effects associated with TI combination therapy are unclear. However, combination therapy with certain TIs should be used with caution until more data are available.
17706536 Nonprosthesis orthopedic applications of (18)F fluoro-2-deoxy-D-glucose PET in the detecti 2007 Jul This article describes the impact of [(18)F]2-fluoro-2-deoxy-D-glucose (FDG) PET in the diagnosis of non-prosthesis-related orthopedic infections and inflammation. FDG-PET has an excellent sensitivity in the detection of osteomyelitis (OM). Early data indicate that FDG-PET may be more specific than MRI in diagnosing OM. The role of the combination of FDG and PET-CT in the diagnosis of OM is likely to be determined as this combination is used on a routine basis. Early data from studies in rheumatoid arthritis indicate that FDG-PET is highly accurate in early diagnosis and that it provides results comparable to the most advanced conventional techniques.
17304682 Camptocormia in a patient with Parkinson disease and a myopathy with nemaline rods. 2007 Jan Camptocormia, also referred to as bent spine, is a gait disorder characterized by hyperflexion of the thoracolumbar spine that develops in recumbent position while walking and that disappears in supine position. Myopathy is one of the frequent causes of camptocormia. A 77-yr-old male patient who was followed up with the diagnosis of rheumatoid arthritis for 2 yrs was admitted with progressive gait deterioration. Hyperflexion of trunk, disappearing in supine position, was detected and diagnosed as camptocormia. He also exhibited the signs of parkinsonism. A paraspinal muscle biopsy showed myopathy with rods in many muscle fibers. Camptocormia in this patient may be attributable to the myopathic weakness of thoracolumbar paraspinal muscles. The normal biceps brachii muscle biopsy refers to the isolated affection of paraspinal muscles in this patient. A camptocormia (bent spine) case of myopathy with nemaline rods associated with Parkinson disease is presented.
17113808 Polymyalgia rheumatica: diagnosis and treatment. 2006 Dec Polymyalgia rheumatica (PMR) typically manifests as inflammatory pain in the shoulder and/or pelvic girdles in a patient over 50 years of age. This condition was long underrecognized and therefore underdiagnosed. Today, however, overdiagnosis may occur. Physicians must be aware that many conditions may simulate PMR, including diseases that carry a grim prognosis or require urgent treatment. PMR may be the first manifestation of giant cell arteritis, and a painstaking search for other signs is mandatory. PMR may inaugurate other rheumatologic diseases such as rheumatoid arthritis, RS3PE syndrome, spondyloarthropathy, systemic lupus erythematosus (SLE), myopathy, vasculitis, and chondrocalcinosis. Finally, PMR may be the first manifestation of an endocrine disorder, a malignancy, or an infection. Failure to respond to glucocorticoid therapy should suggest giant cell arteritis, malignant disease, or infection. Ultrasonography may assist in the diagnosis by showing bilateral subdeltoid bursitis. Glucocorticoids are the mainstay of the treatment of PMR. Although the optimal starting dosage and tapering schedule are not agreed on, a low starting dosage and slow tapering may decrease the relapse rate. Methotrexate is probably useful when glucocorticoid dependency develops. In contrast, TNF-alpha antagonists are probably ineffective.
17033980 [Hypertrophic cranial and spinal pachymeningitis. A description of four new cases and a re 2006 Oct 16 INTRODUCTION: Hypertrophic pachymeningitis is an infrequent disease that is characterised by inflammatory hypertrophy of the dura mater. There are cranial, spinal and craniospinal forms of the disease. They may be due to underlying infectious, autoimmune or neoplastic processes, although most of the cases reported in recent years have no base pathology and are known as idiopathic hypertrophic pachymeningitis. The ideal treatment is unknown, but most cases usually respond well to therapy with corticoids. CASE REPORTS: We report two cases of cranial forms, one idiopathic with typical clinical features consisting in cranial polyneuropathy and good response to corticoids, and another case secondary to rheumatoid arthritis that began with epileptic seizures. Both had a parenchymatous oedema. The two forms of spinal pachymeningitis presented as progressive paraparesis that evolved well after surgical removal of the lesion. CONCLUSIONS: On observing pachymeningitis in neuroimaging tests it becomes necessary to conduct a comprehensive aetiological study in search of infectious, autoimmune and neoplastic diseases. In the cranial forms there may be parenchymatous oedema, which would explain the epileptic seizures and the cognitive deterioration of our patients. Response to corticoids is spectacular, although it is often necessary to continue to administer them for prolonged periods of time.
17030375 Possible antipsychotic effects of minocycline in patients with schizophrenia. 2007 Jan 30 We present two cases of patients with schizophrenia treated with minocycline. Minocycline (a second-generation tetracycline) is an established and safe broad-spectrum antibiotic that crosses the blood-brain barrier, with additional efficacy for diseases such as acne and rheumatoid arthritis. Animal studies have suggested that minocycline may prevent progression of some neurological disorders. Moreover, it has been reported that minocycline might have antidepressant effects. We report two cases of acute schizophrenia with predominant catatonic symptoms that responded to minocycline.
17002220 Inosine 5'-monophosphate dehydrogenase inhibitors for the treatment of autoimmune diseases 2006 Sep Inosine 5'-monophosphate dehydrogenase (IMPDH) is a key enzyme in the de novo biosynthesis of guanine nucleotides. Proliferation of T- and B-lymphocytes, a hallmark of many autoimnunne diseases, is heavily dependent on access to a large pool of guanine nucleotides. To support this activity IMPDH is upregulated. The clinical benefit observed with mnycophenolic acid, a potent IMPDH inhibitor, in a number of autoimmune diseases, including those associated with organ transplantation, rheumatoid arthritis, psoriasis, systemic lupus erythenmatosus and inflammatory bowel disease, has validated IMPDH as an immunosuppressive target, and triggered the search from the pharmaceutical industry for IMPDH inhibitors with best-in-class status. This review will highlight recent advances in the IMPDH field, with a focus on the discovery and development of non-nucleoside IMPDH inhibitors.
16613338 Cholesterol crystals causing falsely elevated automated cell count. 2006 Mar This is a report of 3 cases of body fluid containing numerous cholesterol crystals that caused falsely elevated cell counts on an automated cell counter. Two of the cases were pleural effusion fluid from patients with long-standing rheumatoid arthritis. Fluid in the third case was from upper extremity cystic lesions of a patient with squamous cell carcinoma of the head and neck. Microscopic examination revealed abundant cholesterol crystals in all fluid samples. In all 3 cases, initially, the automated cell counter reported very elevated WBC and RBC counts that were much higher than those from the manual count. This interference by cholesterol in the automated cell counter is discussed. In addition, possible pathophysiology of cholesterol formation in the body fluid is discussed and chylous and pseudochylous (chyliform) effusions are reviewed. Finally, the use of automated instruments in the evaluation of body fluid is reviewed.
16789749 Inhibition of lysosomal cysteine proteases by a series of Au(I) complexes: a detailed mech 2006 Jun 29 Complexes of gold(I) have long been used to treat rheumatoid arthritis although the precise biological targets of gold are not well understood. One intriguing therapeutic target of Au(I) is the cathepsin family of lysosomal cysteine proteases. Here, we present the inhibition of cathepsin B by a known Au(I)-based drug and a series of derivatives. The complexes investigated were reversible, competitive inhibitors with IC50 values ranging from 0.3 to 250 microM, depending on the substituents around the Au(I).
15920734 MT1-MMP: a potent modifier of pericellular microenvironment. 2006 Jan Cells are regulated by many different means, and there is more and more evidence emerging that changes in the microenvironment greatly affect cell function. MT1-MMP is a type I transmembrane proteinase which participates in pericellular proteolysis of extracellular matrix (ECM) macromolecules. The enzyme is cellular collagenase essential for skeletal development, cancer invasion, growth, and angiogenesis. MT1-MMP promotes cell invasion and motility by pericellular ECM degradation, shedding of CD44 and syndecan1, and by activating ERK. Thus MT1-MMP is one of the factors that influence the cellular microenvironment and thereby affect cell-signaling pathways and eventually alters cellular behavior. As a proteinase, MT1-MMP is regulated by inhibitors, but it also requires formation of a homo-oligomer complex, localization to migration front of the cells, and internalization to become a "functionally active" cell function modifier. Developing new means to inhibit "functional activity" of MT1-MMP may be a new direction to establish treatments for the diseases that MT1-MMP mediates such as cancer and rheumatoid arthritis.
17149055 Sphygmomanometry-evoked allodynia--a simple bedside test indicative of fibromyalgia: a mul 2006 Dec BACKGROUND: One of the 2 classification criteria for fibromyalgia (FM) is the presence of tender points on specific anatomic sites. It has been established that these tender points reflect a state of generalized allodynia (defined as pain resulting from a stimulus that does not normally provoke pain). Patients with FM often describe pain elicitation during blood pressure testing (sphygmomanometry). OBJECTIVE: The objective of this study was to define if a universally used clinical test, sphygmomanometry, is helpful in the identification of patients with FM. METHODS: The authors conducted a prospective multicenter study in 3 different public rheumatology outpatient services. Each center studied 20 patients with FM, 20 with rheumatoid arthritis, 20 with osteoarthritis, and 20 healthy individuals. The following question was asked of each participant: "When I take your blood pressure, tell me if the cuff's pressure brings forth pain." The blood pressure cuff was inflated at an approximate rate of 10 mm Hg per second up to 180 mm Hg or to the point when pain was elicited. RESULTS: Sixty-nine percent of patients with FM had sphygmomanometry-evoked allodynia in contrast to 10% of patients with osteoarthritis, 5% with rheumatoid arthritis, and 2% of healthy individuals (P < 0.001). The mean blood pressure value at which allodynia was elicited was lower in patients with FM (143 +/- 40 mm Hg) when compared with the other 3 groups (176 +/- 11 mm Hg) or higher (P < 0.001). In patients with FM, there was a significant negative correlation between the blood pressure value at which allodynia developed and total Fibromyalgia Impact Questionnaire (FIQ) score, number of tender points, and the FIQ visual analog scales for pain intensity and fatigue (P < 0.05). The test yields a diagnostic sensitivity for FM of 0.7, specificity 0.96, positive predictive value 0.86, and negative predictive value 0.91. CONCLUSIONS: In this developmental study of patients attending rheumatology clinics, the generation of pain during blood pressure testing was strongly associated with the diagnosis of FM. This robust linkage probably reflects a tautologic phenomenon. A sine qua nonelement for FM diagnosis is the presence of tender points in discrete anatomic sites. These tender points in turn reflect a state of generalized mechanical allodynia that can be locally elicited by the cuff pressure during blood pressure testing. Sphygmomanometry is a simple bedside test that may be useful in the recognition of patients with FM. Blood pressure testing is a universal procedure in all clinical environments. Based on our results, we suggest searching for FM features in any person who has sphygmomanometry-evoked allodynia.
19337437 Tumor necrosis factor-alpha inhibitor treatment for sarcoidosis. 2008 Dec Sarcoidosis is a chronic multisystem disease of unknown etiology, characterized by noncaseating granulomatous infiltration of virtually any organ system. Treatment is often undertaken in an attempt to resolve symptoms or prevent progression to organ failure. Previous studies have suggested a prominent role for tumor necrosis factor-alpha (TNF-alpha) in the inflammatory process seen in sarcoidosis. TNF-alpha and interleukin-1 are released by alveolar macrophages in patients with active lung disease. Corticosteroids have proved to be efficacious in the treatment of sarcoidosis, possibly by suppressing the production of TNF-alpha and other cytokines. Three agents are currently available as specific TNF antagonists: etanercept, infliximab, and adalimumab. Although data from noncomparative trials suggest that all three have comparable therapeutic effects in rheumatoid arthritis, their effects in a granulomatous disease such as sarcoidosis are less consistent. In this review, current data on the effectiveness are summarized.
18848375 Herniation of the temporomandibular joint into the external auditory meatus secondary to b 2009 Mar The temporomandibular joint (TMJ) is intimately related to the external auditory meatus (EAM). Herniation of the joint into the EAM occurs secondary to neoplasia, trauma, inflammation and developmental problems [Conover GL, Crammond RJ. Tympanic plate fracture from mandibular trauma. J Oral Maxillofac Surg 1985;43:292-4; Ali TS, Rubinstein JT. Rheumatoid arthritis of the temporomandibular joint with herniation into the external auditory canal. Ann Otol Rhinol Laryngol 2000;109:177-9]. Benign necrotising otitis externa (BNOE) is an uncommon condition characterized by avascular necrosis of the tympanic plate that has been described as a sequela of simple otitis externa. [Wormald PJ. Surgical management of benign necrotizing otitis externa. J Laryngol Otol 1994;108:101-5.] We present a case of BNOE that resulted in a posterior herniation of the TMJ capsule into the EAM.
18817638 Spondyloarthritis at the crossroads of imaging, pathology, and structural damage in the er 2008 Oct Ankylosing spondylitis (AS) is characterized by two key pathologic findings: sacroiliac joint and spinal inflammation and new bone formation with possible bone fusion, usually in the axial skeleton. Thus, structural damage in AS must be viewed differently than that in rheumatoid arthritis. Tumor necrosis factor blockers effectively inhibit inflammation, as shown by signs and symptoms, function, C-reactive protein, and MRI, and will probably prevent erosive structural damage. However, the ossification of already-damaged bone cannot be influenced by tumor necrosis factor blockade, because these drugs do not inhibit osteoblasts. It remains to be seen whether additional targeting of new bone formation is clinically meaningful in advanced AS. The most important action to prevent structural damage is probably an early diagnosis and effective anti-inflammatory treatment of AS.
18774919 Plasmid DNA as a safe gene delivery vehicle for treatment of chronic inflammatory disease. 2008 Oct BACKGROUND: The development of plasmid DNA (pDNA) vectors for safe and efficacious gene transfer therapy for chronic inflammatory diseases is a natural sequel to biological therapies which, whilst effective, are relatively expensive, require frequent administration and are not suitable for all patients. OBJECTIVE: To outline the methods of non-viral gene therapy using pDNA and detail research on potential targets in the treatment of chronic inflammatory diseases, with particular emphasis on multiple sclerosis, rheumatoid arthritis and osteoarthritis. METHODS: A comprehensive online journal search was used to examine current approaches in pDNA transfer and practical applications in chronic inflammatory diseases; conditions with similar disease processes were also considered. RESULTS/CONCLUSION: Significant progress has been made in increasing the efficiency and efficacy of non-viral gene transfer. For modulation of inflammatory targets, the conversion of biological therapy to gene therapy using pDNA is achievable.
18503993 Chronic GVHD as an autoimmune disease. 2008 Jun Many of the clinical, histological and serological manifestations of chronic graft-versus-host disease (GVHD) resemble autoimmune disease (AD), and although the differences are significant, they may be more semantic than biological. Indeed, studies suggest that some ADs may represent a fetal-versus-maternal chronic GVHD. Both conditions involve dysregulated immune responses resulting in tissue inflammation, damage, scarring and organ dysfunction, and both may be associated with a genetic predisposition. Epitope-specific autoaggressive phenomena such as immune thrombocytopenic purpura (ITP) are often seen following allogeneic hematopoietic stem-cell transplantation (HCT), implying a loss of specific tolerance to self structures. However, the more widespread manifestations of GVHD such as the well-known scleroderma-like symptoms differ in many fundamental respects from de-novo scleroderma, and other multisystem ADs such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA).
18419456 Vaccination in patients with chronic rheumatic or autoimmune diseases. 2008 May 1 Patients who have chronic rheumatic or autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, or vasculitides, show a risk of infection that is at least 2-fold greater than that for healthy individuals. This increased risk is not only a result of the aberrant immunologic reaction itself but also can be attributed to the immunosuppressive therapy required to control the activity of the underlying disease and the associated organ complications. Vaccination is an option for a substantial number of these infections. In this context, pneumococcal and influenza vaccines are the best evaluated and are recommended by standard vaccination guidelines. Some studies have found mildly impaired immune responses to vaccines among patients receiving long-term immunosuppressive therapy, but postvaccination antibody titers are usually sufficient to provide protection for the majority of immunized individuals. The accumulated data on the safety and effectiveness of vaccines warrant immunization with the majority of vaccines for patients with chronic autoimmune or rheumatic diseases, especially vaccination against influenza and pneumococci. Vaccination protocols for this population should be better implemented in daily clinical practice.
18188659 Polymyalgia rheumatica/arteritis temporalis and acquired factor VIII inhibitor. 2008 Jun Acquired haemophilia is a rare, but often life-threatening bleeding disorder caused by autoantibodies, mostly directed against factor VIII (FVIII inhibitor). The incidence of acquired haemophilia, which most commonly affects patients over 50 years of age, is estimated between 0.2 and 1 million per year. Although its aetiology remains obscure, 40-50% of cases are associated with other conditions, such as pregnancy, malignancies, drugs and autoimmune disorders as rheumatoid arthritis, systemic lupus erythematosus and Sjögren's disease. We report the case of a 69-year-old patient with spontaneously acquired FVIII inhibitor secondary to polymyalgia rheumatica (PMR)/arteritis temporalis (AT). Our case illustrates that PMR/AT can be added to the list of autoimmune disorders associated with acquired haemophilia due to FVIII inhibitor.