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ID PMID Title PublicationDate abstract
16735009 Current concepts in gene therapy of the musculoskeletal system. 2006 Apr The purpose of this article is to review the remarkable progress in the field of musculoskeletal system gene therapy. Since the introduction of this concept 15 years much of the preclinical and clinical data have emerged. The original target, rheumatoid arthritis, has been subjected to clinical phase II efficacy protocol, and osteoarthritis gene therapy efficacy is being thoroughly investigated in various animal models. The most promising area of research in this field however, is the tissue repair, because it doesn't require prolonged period of gene expression, local delivery is reasonably simple and it avoids substantial risk associated with systemic delivery, and levels of gene expression don't need to be so finely regulated. Gene transfer is successfully being used to aid the repair and regeneration of bone, cartilage, ligament tendon, meniscus and intervertebral disc. Other potential applications of gene therapy in musculoskeletal system include osteoporosis, aseptic loosening, genetic diseases and tumors. Highly encouraging data gained from these studies have confirmed that gene therapy is a promising therapeutic solution to treat various musculoskeletal system disorders.
16582688 An update on osteoarthritis therapeutics. 2006 May PURPOSE OF REVIEW: This review addresses recent major developments in symptomatic therapy and the principles of disease modification in osteoarthritis. It emphasizes issues that are of importance to the practicing clinician at a time when researchers in the field are trying to improve ways not only to provide symptomatic relief but also to slow disease progression. RECENT FINDINGS: The past year has led to a reassessment of the role of cyclo-oxygenase-2 inhibitors in osteoarthritis therapy and has yielded new information on nutriceuticals such as glucosamine. The relative efficacy of intra-articular injections of agents such as corticosteroid and hyaluronic acid preparations has been assessed. In addition, reports on trials of potentially disease-modifying agents for osteoarthritis have been published. SUMMARY: Because the therapeutic options have been reduced over the past year and the role of nutritional supplements remains unclear, the clinician is faced with a need to reassess osteoarthritis therapy. Although no practical disease-modifying agent for osteoarthritis has been identified, reports such as the recent doxycycline trial reviewed herein provide hope that continued research will soon yield a therapeutic model similar to that used in rheumatoid arthritis, for which some therapeutic agents achieve disease modification and other agents can be added as needed for symptomatic relief.
16265287 Diagnosis and treatment of a patient with gallstone ileus. 2005 Jul BACKGROUND: A 79-year-old white woman presented with upper abdominal pain. She had a history of rheumatoid arthritis since she was 19 years old, which was treated with prednisolone, leflunomide, diclofenac and pantoprazole. She also had factor VII deficiency. The patient had been hospitalized 2 months previously with sepsis presumed to be due to urinary infection, and was treated with antibiotics. Sonography at this time revealed a gallbladder with a monstrous thick wall and stones, and the first differential diagnosis was cholecystitis. Cholecystectomy was planned after amelioration of the patient's general state, but her general state worsened. INVESTIGATIONS: Sonography, endoscopy of the upper and lower intestine, and CT scan. DIAGNOSIS: Biliodigestive fistula and gallstone ileus. MANAGEMENT: Enterolithotomy, stenting, endoscopic retrograde cholangiopancreatography, and surgery.
15911271 Inhibition of IKK-2 by 2-[(aminocarbonyl)amino]-5-acetylenyl-3-thiophenecarboxamides. 2005 Jun 2 A series of 21 novel 2-[(aminocarbonyl)amino]-5-acetylenyl-3-thiophenecarboxamides were synthesized and evaluated for the inhibition of IKK-2. In spite of their often modest activity on the enzyme, six selected analogs showed significant inhibition of the production of inflammatory cytokine IL-8 in IL-1beta stimulated rheumatoid arthritis-derived synovial fibroblasts, demonstrating their potential usefulness as NF-kappaB regulators.
15847029 Troponins: current status in coronary artery disease. 2005 Feb The acute coronary syndromes (ACS) represent a pathological, diagnostic and risk continuum from unstable angina (UA) through myocardial infarction (MI) with or without ST segment elevation. The past 12 years have seen extensive investigations into the use of various cardiac markers to establish the diagnosis and prognosis in ACS and to evaluate perfusion after thrombolysis. The Troponins comprise a group of three proteins (C, I and T) which interact with tropomyosin to form a troponin-tropomyosin complex. Troponin-T is a structural component of the troponin complex and is known to exist in three isoforms. Troponins have both diagnostic, post-event risk stratification and prognostic significance. Apart from myocardial infarction however they are raised in several conditions like Myocarditis, dilated Cardiomyopathy, Severe congestive cardiac failure, severe pulmonary embolism with right ventricular strain and Preterm infants with respiratory distress. False positives have been reported with Angioplasty, cardiac surgery, RF ablation, Allograft rejection following cardiac transplant and seropositive rheumatoid arthritis. False negatives have been reported with early sampling, early reading, use of wrong anticoagulant, clotted blood, careless storage of kits. Significantly, lower troponin values have been reported in heparinised plasma than in serum.
15820488 Anti-cyclic citrullinated peptide autoantibodies measured by an automated enzyme immunoass 2005 May BACKGROUND: Autoantibodies against cyclic citrullinated peptide (anti-CCP) are considered to be a sensitive and specific marker for rheumatoid arthritis (RA). This study evaluated the analytical performance and clinical correlation of an automated enzyme immunoassay (DSX, DINEX Technologies), for the detection of anti-CCP autoantibodies (DIASTAT anti-CCP, Axis-Shield, DUNDEE UK). METHODS: Commercial controls and serum pools were used to determine its precision, analytical sensitivity, functional sensitivity and linearity. Sera from 83 patients with established RA and from 140 controls, including patients with various autoimmune diseases, viral infections and cancer, as well as sex- and age-matched healthy subjects, were studied. The rheumatoid factor (RF) was also assayed in each sample, and the results were compared to the anti-CCP findings. RESULTS: The total imprecision (CV%) was 4.7-7.2% for concentrations ranging between 1.98 and 71.81 U/mL. The lower detection limit was 0.038 U/mL. At a cut-off of 5 U/mL, the sensitivity and specificity for RA were 67.5% and 99.3%, respectively. The RF had a sensitivity of 66.3% and a lower specificity 82.1% than anti-CCP. When the two antibodies were used together, the specificity was 99.1%. CONCLUSIONS: The anti-CCP assay we examined on a fully automated system showed a good analytical performance (analytical and functional sensitivity, linearity) and good clinical correlation. We conclude that this system can provide rapid, useful data.
15604911 Central nervous system manifestations of rheumatologic diseases. 2005 Jan PURPOSE OF REVIEW: To summarize the current literature on central nervous system manifestations of vasculitides and connective tissue diseases. RECENT FINDINGS: There have been advances in understanding the mechanisms behind the initiation and perpetuation of inflammatory processes in vasculitic neuropathy. Clinically relevant data have been obtained on the predictive criteria for a positive biopsy result in giant cell arteritis, the imaging characteristics of primary angiitis of the central nervous system, and Behçet disease, and the clinical and radiologic features of neuro-Behçet disease. There is more clarity about the central nervous system syndromes attributable to systemic lupus erythematosus and new insights into the central mechanisms involved in the manifestations of Sjögren syndrome and rheumatoid arthritis. Novel immunomodulatory agents, such as infliximab, have shown some benefit in rheumatoid vasculitis and Sjögren syndrome. SUMMARY: A better understanding of the clinical, radiographic, and serologic characteristics of various central nervous system complications of rheumatologic diseases has been gained in the past year. Recent advances in understanding the pathophysiology of peripheral nervous system complications and their treatment may affect the management of the central nervous system complications.
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.
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).
16308554 [Superficial US of superficial bones]. 2005 Dec Although bones are not well imaged by US this imaging modality can be helpful in the assessment of bone surface and can be complementary to standard radiographs. A focal irregularity of the hyperechoic cortical line indicates a fracture, a cortical avulsion, a local bulging of the cortex or a foreign body related or not to previous surgery. Subperiosteal collections either purulent or hemorrhagic are easily detected and can be aspirated under US guidance if an infection is suspected. US also allows diagnosis of epiphyseal fractures when involving the distal epiphysis of the metatarsals, radial head, humeral head (Hill-Sachs fracture) growing cartilages... US examination of joints can detect osteophytes and marginal erosions (allowing early diagnosis of rheumatoid arthritis together with visualization of hyperaemic pannus and joint effusion) Cortical continuity in a location where in normal conditions a joint space is found indicates a synostosis. In children US, by directly visualizing the cartilaginous component of the non ossified bones, allows detection and serial follow-up of many congenital malformation (pes equinus...). US may be obtained in all patients where standard radiographs are not diagnostic because of it is efficient, non-invasive and relatively inexpensive.
16276043 [B lymphocyte]. 2005 Oct Recent studies have revealed that B cells play a critical role in autoimmunity and disease expression through various functions, including autoantibody production, cytokine secretion, antigen presentation, and co-stimulatory effect. Selective targeting of B cells has been recently achieved using a chimeric monoclonal antibody against CD20 (Rituximab). Significant clinical efficacy has been demonstrated in several autoimmune diseases including rheumatoid arthritis and systemic lupus erythematosus by the infusion of this antibody. Rituxumab significantly improves the symptoms during the long period of complete B cell depletion. Understanding the dynamics of B cell involvement in autoimmune diseases will be crucial to the development of B cell-targeted strategies. Conversely, the findings derived from studies of anti-B cell therapy provide us a lot of important clues to clarify the pathogenesis of autoimmune diseases. This review focuses on recent data demonstrating the roles of B cells in autoimmune diseases as well as the current studies concerning the treatment of autoimmune diseases by Rituximab.
16189636 Microscopic polyangiitis after silicone breast implantation. 2005 Sep We describe the case of a patient who developed microscopic polyangiitis (MPA) after silicone breast implantation. A 60-year-old woman who had undergone silicone breast implantation was admitted to our hospital with complaints of general malaise and hematoproteinuria. She was diagnosed as having MPA with evidence of acute progressive renal failure, pulmonary hemorrhage, and positivity for myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA). A renal biopsy showed severe necrotizing and crescentic glomerulonephritis with arteriolitis. The patient received high-dose steroids and plasma exchange treatment, but died of progressive pulmonary hemorrhage and multiple cerebral hemorrhage. Silicone implantation is associated with scleroderma, systemic lupus erythematosus, and rheumatoid arthritis. This case report indicates the possibility of the development of MPA after silicone breast implantation.
16112533 The commercial harvest of devil's claw (Harpagophytum spp.) in southern Africa: the devil' 2005 Sep 14 Devil's claw is the common name for two species in the genus Harpagophytum. Their root extracts contain the iridoid glycoside, harpagoside, which has been found to be effective in the treatment of degenerative rheumatoid arthritis, osteoarthritis, tendonitis, kidney inflammation, and heart disease. Most of the world's supply comes from Namibia, with lesser amounts from South Africa and Botswana. In 2002, the peak year of export, 1018 tonnes of dried tubers were exported from southern Africa, representing the harvest of millions of plants. In 2001, sales in Germany were estimated at 30 M euros, accounting for 74% of the prescriptions for rheumatism. Harvest has improved income levels in marginalized communities but it has also raised questions of sustainability. In 2000, recommendations were made to the Convention on the International Trade in Endangered Species (CITES) to add devil's claw to Appendix II. In 2004, the proposal was formally withdrawn due to the efforts of the range states to address sustainability issues. Replacing wild collection with cultivation has generated a debate on the positive and negative effects on harvester income and rural farmers. Successful cultivation efforts have involved micropropagation techniques and growing the plant without water or fertilizers. The governments of the main range states are working with local communities to develop policies and regulations to protect the species and to determine a sustainable harvest.
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.
15674369 Differential cytokine genotype frequencies among Canadian Aboriginal and Caucasian populat 2005 Mar Genetic diversity related to the human immune response is a key factor in individual and population survival throughout human history. Population diversity in disease susceptibility and resistance have been identified and linked to differences in cytokine mRNA and protein expression levels. Polymorphisms in the regulatory regions of cytokine genes can influence gene transcription levels and they have been associated with susceptibility to, and/or severity of, autoimmune disorders such as rheumatoid arthritis, meningococcus and sepsis. It is reported here that in two study populations, Canadian Aboriginal individuals have a higher frequency of cytokine single-nucleotide polymorphisms favouring a low production of TNFalpha, IFNgamma and IL-10 and high production of IL-6 as compared to a Caucasian population. We postulate that the evolution of this unique cytokine genotype profile may be linked to the Aboriginal adaptation to selection pressures related to an environment in which helminthic, parasitic and fungal infections predominated.