Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
9140134 The potential role of iron chelators in the treatment of Parkinson's disease and related n 1997 Apr Neurodegeneration is characterized by a marked accumulation of iron in the affected brain regions. The reason for this is still unknown. In this article we review the available data on the possible involvement of iron and mediated oxidative stress in the aetiology of Parkinson's disease and related disorders. Iron chelators, if they effectively prevent radical formation, have great therapeutic potential against ischaemia/reperfusion, rheumatoid arthritis, and anthracycline toxicity, which are most likely free radical-mediated. The efficacy of the best established chelating drug desferal in neurodegenerative disease is limited due to its high cerebro- and oculotoxicity. New bioactive chelating agents are currently being developed, among them are oxidative stress activatable iron chelators which are most likely less toxic and can flexibly respond to an increase of free radical formation in the cell.
9121002 [A comparative study of the ELISA and IF methods for antinuclear antibody test]. 1997 Feb A new ELISA method for antinuclear antibody(ANA) test was investigated for its clinical usefulness by comparison with a widely used IF method. Both methods used Hep 2 cells as a substrate. ELISA method showed good reproducibility in both within-run(CV = 5.1 approximately 8.7%) and between-run(CV = 8.1 approximately 9.6%) assays. ROC analysis revealed that ELISA method had a higher sensitivity and an equal specificity as compared to IF method. Application of an auto analyzing system to ELISA method could induce the improvement of efficacy and labor saving. The coincidence rate between ELISA and IF methods was 78.6% on the samples from 887 patients with various disorders. In patients with drug induced lupus or connective tissue diseases except for rheumatoid arthritis, the discrepancies were caused mainly by the higher sensitivity of ELISA method. However, the ELISA test was less sensitive for the ANAs showing granular, nuclear membrane, or anti-PCNA antibody like staining patterns by IF method. In conclusion, ELISA method is useful for detecting ANAs because of its high sensitivity and efficiency, though it still has some points to be improved.
16180173 ABX-CBL (Abgenix Inc). 1999 Jan Abgenix has acquired rights to ABX-CBL, an antibody in phase II trials for the potential treatment of graft versus host disease (GvHD). The antibody, previously known as CBL-1 was discovered by the CV Cancer Center. Abgenix planned to continue phase II trials in GvHD in 1998 after completing a confirmatory clinical study required by a manufacturing process change. ABX-CBL will also be evaluated in kidney and other organ transplant rejection indications. In January 1998, Abgenix announced that it had commenced a phase II trial of the antibody at eight clinical centers to confirm the results of previous phase II trials. The study will involve 48 patients. Results of the trial were expected by the third quarter of 1998. However, by December 1998 they had not been reported. ABX-CBL could also potentially be used to treat inflammation and autoimmune diseases such as rheumatoid arthritis and psoriasis. In a clinical trial, ABX-CBL was administered to ten patients with acute steroid-resistant GvHD. The overall response rate was 90%, with GvHD completely resolved in five patients and improved by at least two grades in four others. The antibody was well-tolerated and did not exacerbate post-transplant immunodeficiency. In another study involving 43 patients who developed GvHD after kidney transplant, ABX-CBL was effective in reversing the first rejection and preventing recurrence of rejection. It was shown to be well tolerated with no serious adverse events reported.
11578010 D-penicillamine is not an effective treatment in systemic sclerosis. 2001 Based on open studies. D-penicillamine (DPA) has been used for the treatment of systemic sclerosis (SSc) but we believe the controlled trial of this drug in SSc does not support its use to treat this disease. Open trials are inevitably biased by selection bias and randomized, blinded, controlled studies are required to minimize both known and unknown confounding variables. The high vs. low dose DPA trial was a well-controlled, randomized, double-blind study which met criteria for a high quality study, although it was not placebo-controlled. Toxicity was increased in the high dose group, thus showing a biologic response, although the study showed no clinical efficacy differences between a mean dose of 120mg DPA every other day (equivalent to 60mg qd) and a mean dose of 822mg DPA daily. One might argue that 60mg DPA is effective, but we believe this is highly unlikely, as doses significantly higher than this have been shown to be ineffective in other connective tissue diseases such as rheumatoid arthritis. In our opinion. D-penicillamine is, unfortunately, ineffective in treating early, diffuse, systemic sclerosis.
11496827 [Induction of histidine decarboxylase in inflammation and immune responses]. 2001 Jul Histamine is a classical, but still interesting inflammatory mediator. Many people have long believed that histamine is derived from mast cells or basophils alone. However, the histamine-forming enzyme, histidine decarboxylase (HDC), is induced in a variety of tissues in response (i) to gram-positive and gram-negative bacterial components (lipopolysaccharides, peptidoglycan, and enterotoxin A) and (ii) to various cytokines (IL-1, IL-3, IL-12, IL-18, TNF, G-CSF, and GM-CSF). HDC is induced even in mast-cell-deficient mice. The histamine newly formed via the induction of HDC is released immediately and may be involved in a variety of immune responses. Reviewing our work and that of Schayer and Kahlson, the pioneers in this field, lead us to the conclusion that nowadays we need to understand that histamine can be produced via the induction of HDC by a mechanism coupled with the cytokine network. We call this histamine "neohistamine", to distinguish it from the classical histamine derived from mast cells or basophils. Neohistamine is involved in physiological reactions, inflammation, immune responses and a variety of diseases such as periodontitis, muscle fatigue (or temporomandibular disorders), stress- or drug-induced gastric ulcers, rheumatoid arthritis, complications in diabetes, hepatitis, allograft rejection, allergic reactions, tumor growth, and inflammatory side effects of aminobisphosphonates.
11385927 Tenosynovitis of the posterior tibial tendon. 2001 Mar PTT tenosynovitis is a recognized entity no longer confused with an ankle sprain. Three possible causes are (1) overuse or age related (mechanical in cause, true stage I disease), (2) seronegative spondyloarthropathies (clinical suspicion, hematologic analysis), and (3) rheumatoid arthritis (deformity may be owing to ligamentous or capsular destruction). The PTT has a hypovascular zone 40 mm proximal to the insertion of the tendon and 14 mm in length. Pain often is localized to this portion of the tendon (primarily in stage I disease). Ultrasound is an inexpensive and accurate method to assist in the diagnosis of this condition and may replace MR imaging as more experienced ultrasonographers appear. The initial management of PTT tenosynovitis includes tendon rest and nonsteroidal anti-inflammatory medication and physical therapy. Surgical synovial débridement is performed early (6 weeks) in patients with enthesopathies (seronegative disease). This procedure may be delayed 3 months in patients with true stage I disease. At surgery, the undersurface of the tendon must be inspected for longitudinal split tears, and these must be repaired with nonabsorbable suture, burying the knots. The excursion of the tendon should be checked intraoperatively. Patients with stage I disease should be evaluated carefully for preoperative structural deformity to choose the appropriate surgical procedure and prevent failure of isolated tenosynovectomy.
10974304 Serum prolactin levels in Behçet's disease. 2000 Jul PURPOSE: Evaluation of serum prolactin levels in Behçet's disease patients in Turkey. METHODS: Serum prolactin levels were measured by radioimmunoassay (RIA) in 17 patients with ocular findings, and 20 patients without ocular findings of Behçet's disease, and in 17 healthy volunteers. RESULTS: The average prolactin levels were measured as 9.53 ng/mL in patients with ocular findings, 8.84 ng/mL in patients without ocular findings, and 9.59 ng/mL in healthy controls. There was no statistical significance among these three groups. Also, the average levels were 9.84 ng/mL in remission periods and 7.54 ng/mL in attacks. CONCLUSIONS: In some studies, it has been suggested there is a correlation between high serum prolactin levels and activation of some autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. However, we found no such correlation in Behçet's disease. On the contrary, prolactin levels were lower in attacks than in remissions.
10968781 Therapeutic approaches to bone diseases. 2000 Sep 1 The strength and integrity of our bones depends on maintaining a delicate balance between bone resorption by osteoclasts and bone formation by osteoblasts. As we age or as a result of disease, this delicate balancing act becomes tipped in favor of osteoclasts so that bone resorption exceeds bone formation, rendering bones brittle and prone to fracture. A better understanding of the biology of osteoclasts and osteoblasts is providing opportunities for developing therapeutics to treat diseases of bone. Drugs that inhibit the formation or activity of osteoclasts are valuable for treating osteoporosis, Paget's disease, and inflammation of bone associated with rheumatoid arthritis or periodontal disease. Far less attention has been paid to promoting bone formation with, for example, growth factors or hormones, an approach that would be a valuable adjunct therapy for patients receiving inhibitors of bone resorption.
10794239 Insidious destruction of the hip by Mycobacterium tuberculosis and why early diagnosis is 2000 Apr Tuberculosis has re-emerged as an important problem in the United States. More than 10 million people presently are infected with Mycobacterium tuberculosis in the United States alone. The symptoms at first presentation of the disease have become more diverse. With extrapulmonary manifestations, such as musculoskeletal infections, as the sole presenting sign, it often can be difficult to determine the correct diagnosis early in the course of the disease. The presenting symptoms, physical signs, and radiographic findings of intra-articular tuberculosis can mimic those of other intra-articular diseases, such as rheumatoid arthritis, osteoarthritis, and avascular necrosis. In view of the nonspecific findings early in course of the disease, tubercular infection should be considered in the differential diagnosis when there is insidious articular destruction. Failure to consider tuberculosis can lead to devastating outcomes otherwise preventable with today's chemotherapies.
10778663 Essential fatty acids in health and disease. 1999 Sep Essential fatty acids (EFAs) form an important component of cell membranes, are eicosanoid precursors and are therefore required for both the structure and function of every cell in the body. EFAs can modulate the activity of protein kinase C, T and B cell response, free radical generation and lipid peroxidation, lymphokine secretion and cell proliferation. EFAs also have anti-mutagenic, anti-bacterial, anti-fungal and anti-viral properties. EFAs and their metabolites lower serum cholesterol, triglycerides and blood pressure. EFAs appear to be of benefit in atopic eczema, premenstrual syndrome, psoriasis, auto-immune disorders especially rheumatoid arthritis and systemic lupus erythematosus, prevention of target organ damage in diabetes mellitus, peptic ulcer disease, ulcerative colitis, coronary heart disease and atherosclerosis. EFAs and their metabolites can selectively kill tumor cells both in vitro and in vivo without harming normal cells. In addition, EFAs seem to play a fundamental role in inflammation and immune response. In view of their actions and relative safety, it is anticipated that EFAs may be useful in the management of several diseases.
10714209 [New findings in orthopedic pathology]. 1999 The term orthopedic pathology refers to bone- and joint-affecting diseases which are important for the orthopedic surgeon. In the report presented here, emphasis is placed on the membrane-associated proteolysis, which is essential for the degradation of the extracellular matrix. Matrix-degrading processes play a role not only in arthrosis but also in rheumatoid arthritis. Moreover, they are strongly associated with the problem of loosening of protheses, which is of utmost importance for the orthopedic surgeon. In these processes, major roles are played by the plasminogen activator system, plasmin, different matrix metalloproteinases, including the membrane type matrix metalloproteases and different cathepsins. A deeper insight into the function of these proteins and their influence on the matrix degradation in joint diseases will open the way for new diagnostic and therapeutic strategies. Investigations into a large number of chondrosarcomas have shown that for this type of bone lesions, urokinase plasminogen activator and cathepsin B are prognostic parameters that are independent of the differentiation grade. Also, in this context, investigations into the membrane-bound proteases will be of great practical and diagnostic value.
10551177 Periodontal manifestations of collagen vascular disorders. 1999 Oct Chronic degeneration of connective tissue components can be produced by a variety of autoimmune mechanisms. The designations connective tissue disease and collagen-vascular disease are commonly used to describe such conditions when a patient exhibits chronic, immune-mediated deterioration of connective tissue structures in a systemic distribution. Recognized conditions that fit this definition include rheumatoid arthritis, lupus erythematosus, progressive systemic sclerosis, CREST syndrome, and mixed connective tissue disease. Several characteristic oral manifestations of these conditions are recognized. Xerostomia associated with any of these conditions in addition to dryness of the eyes is the definition of secondary Sjögren's syndrome. Fibrosis of facial skin and the resulting limited jaw opening are diagnostic features of progressive systemic sclerosis. Several periodontal manifestations are associated with these connective tissue disorders. Dramatic periodontal ligament space widening that is associated with some cases of progressive systemic sclerosis has been appreciated for more than five decades. However, it has been more recently reported that the majority of progressive systemic sclerosis patients exhibit at least subtle generalized periodontal ligament widening when intraoral radiographs are carefully evaluated. This finding is, however, of limited periodontal significance because the teeth are typically not mobile. Comparisons of periodontitis indices such as pocket depth between healthy subjects and patients with progressive systemic sclerosis do not reveal significant differences (21). In addition, recent evidence suggests a tendency for more severe or progressive manifestations of periodontitis as a consequence of xerostomia that may result from these diseases.
10393072 Psychosocial adjustment of children with chronic illness: an evaluation of three models. 1999 Jun This study was designed to assess social, emotional, and behavioral functioning of children with chronic illness and to evaluate three models addressing the impact of chronic illness on psychosocial functioning: discrete disease, noncategorical, and mixed. Families of children with cancer, sickle cell disease, hemophilia, and juvenile rheumatoid arthritis participated, along with families of classroom comparison peers without a chronic illness who had the closest date of birth and were of the same race and gender (COMPs). Mothers, fathers, and children provided information regarding current functioning of the child with chronic illness or the COMP child. Child Behavior Checklist and Children's Depression Inventory scores were examined. Results provided support for the noncategorical model. Thus, the mixed model evaluated in this study requires modifications before its effectiveness as a classification system can be demonstrated.
10340557 Vasculitic peripheral ulcerative keratitis. 1999 Mar The onset of peripheral ulcerative keratitis in the course of a connective tissue disorder, such as rheumatoid arthritis, relapsing polychondritis, or systemic lupus erythematosus, may reflect the presence of potentially lethal systemic vasculitis. Moreover, peripheral ulcerative keratitis may be the first sign of systemic necrotizing vasculitis in patients with Wegener's granulomatosis, polyarteritis nodosa, microscopic polyangiitis, or Churg-Strauss syndrome. Although the exact pathogenesis of this severe corneal inflammation and destruction is not well understood, evidence points to a dysfunction in immunoregulation with immune complexes formed in response to autoantigens or to some unknown microbial antigen depositing in scleral and limbal vessels. These events lead to changes that are mainly responsible for the resulting tissue damage. In pauci-immune vasculitides positive for antineutrophil cytoplasmic antibodies, cell-mediated cytotoxicity may play an important role in the pathogenesis of peripheral ulcerative keratitis. Untreated systemic conditions such as those mentioned above may carry a grave prognosis for the eye and may also be life-threatening. Immunosuppressive therapy with corticosteroids and cytotoxic agents is, we believe, mandatory in the treatment of these multisystem disorders associated with vasculitic peripheral ulcerative keratitis.
10210231 Antisense and nuclear medicine. 1999 Apr Despite many uncertainties concerning mechanism, synthetic single-strand antisense deoxyribonucleic acids (DNAs) are now in clinical trials for the chemotherapy of viral infections such as human immunodeficiency virus (HIV) and human papilloma virus; several cancers, including follicular lymphoma and acute myelogenous leukemia; inflammatory processes such as Crohn's disease and rheumatoid arthritis and in allergic disorders. There are approximately 10 trials, and early results are generally encouraging. Therefore, the expectation is that antisense DNAs will be important to future chemotherapy. The question considered here is whether antisense DNAs will also be important to future nuclear medicine imaging. While efforts toward developing antisense imaging are comparatively nonexistent thus far, investigations into the mechanisms of cellular transport and localization and the development of a second generation of antisense DNAs have occurred largely within the antisense chemotherapy industry. Fortunately, many of the properties of DNA for antisense imaging, such as high in vivo stability and adequate cell membrane transport, are the same as those for antisense chemotherapy. Unfortunately, interests diverge in the case of several other key properties. For example, rapid localization and clearance kinetics of the radiolabel and prolonged retention in the target are requirements unique to nuclear medicine. No doubt the development of antisense imaging will continue to benefit from improvements in the antisense chemotherapy industry. However, a considerable effort will be required to optimize this approach for imaging (and radiotherapy). The potential of specifically targeting virtually any disease or normal tissue should make this effort worthwhile.
9927902 Relationships between chronic oral infectious diseases and systemic diseases. 1998 Aug There are over 300 species of bacteria forming populations of several hundred billion in the human oral cavity. The number of bacteria reaches a thousand billion when the mouth is not sufficiently cleaned. Using saliva and gingival crevicular fluid as their main nutrients, these bacteria create their ecological niches on tooth surfaces, gingival crevices, saliva, dorsum linguae, and buccal and pharyngeal mucosa, threatening oral and systemic health. It is known that primary lesions of these chronic bacterial infections secondarily cause nephritis, rheumatoid arthritis, and dermatitis. Further, it has been demonstrated in recent years that bacteria inhabiting the oral cavity can cause bacterial pneumonia and endocarditis and that the periodontal-disease-associated bacteria become causative agents for pregnancy troubles and are involved in blood circulation problem and coronary heart disease. Dentistry reviewed the theme of World Health Day, Oral Health for a Healthy Life, in 1994. The 8020 campaign to promote tooth care is also becoming established in Japan; however, the authors emphasized that this achievement is not the goal of dental health care. In this article, we explain the bases supporting the concept that oral health care, primarily mouth cleaning, is important for not only oral disease but also a healthy life.
9781029 Assignment of gene responsible for progressive pseudorheumatoid dysplasia to chromosome 6 1998 May Progressive pseudorheumatoid dysplasia is an autosomal recessive skeletal dysplasia with radiographic changes in the spine similar to Spondyleopiphyseal dysplasia tarda and clinical, though not radiographic resemblance to rheumatoid arthritis. About two-thirds of the reported patients are of Arabic and Mediterranean origin which reflects the relative high incidence in this population. We performed homozygosity mapping utilising the DNA pooling approach to map progressive pseudorheumatoid dysplasia to a chromosomal region on the long arm of chromosome 6. We examined a possible candidate gene in the same region of linkage, namely COL10A1, for alterations in this disorder. We did not identify any mutations in our family, but did not totally exclude COL10A1 gene from being the disease-causing gene.
9741438 Bipolar shoulder arthroplasty for painful conditions of the shoulder. 1998 Sep Between April 1991 and March 1997, 182 bipolar shoulder replacements were implanted in 174 patients (8 bilateral) for painful conditions of the shoulder. The study group comprises 108 patients who were followed for an average of 2.9 years (range, 2-6 years). Diagnoses included osteoarthritis (51), rotator cuff arthropathy (27), avascular necrosis (3), revisions (8), rheumatoid arthritis (2), and fractures--both old and recent (17). A satisfactory rating (University of California at Los Angeles shoulder rating score greater than or equal to 28 points of 35) was achieved by 72% of the patients (including rotator cuff arthropathy patients). Patients with osteoarthritis obtained 90.2% of satisfactory results (46 of 51). The overall pain score after surgery was 8.8 points (of 10), meaning that none or occasional pain was present. Five patients required prosthetic revision, and 102 (94.4%) were satisfied with the surgical procedure.
9651074 Prevalence of the major rheumatic disorders in the adult population of north Pakistan. 1998 May The prevalence of rheumatic diseases in developing countries is largely unknown. Studies which allow comparison of data within the contrasting communities of the Third World and the developed world have the potential to provide insights into disease aetiologies. The current study compared the frequency of rheumatic symptoms (point prevalence) amongst 1997 adults distributed evenly between poor rural and poor urban communities and relatively affluent urban people. Comparisons were also made with similarly but previously derived prevalence rates of rheumatic symptoms and rheumatoid arthritis (RA) in south Pakistan and Pakistanis in England. A significantly higher prevalence of joint pain was seen in the north compared with the south. RA was more common in the north and similar to the frequency amongst Pakistanis resident in England. Ethnic and genetic susceptibility might have accounted for this. There was significantly more soft-tissue rheumatism and back pain in the northern rural population compared with those in the city. Fibromyalgia was almost completely absent from the urban affluent, but osteoarthritis of the knee was significantly more common in this community, perhaps due to relative obesity. RA was least in the urban poor, a phenomenon that might be attributable to earlier death of females or other undetermined factors.
9350230 Gold: an allergen of growing significance. 1997 Aug Gold moved into the limelight of medical literature thanks to the anti-inflammatory activity and effectiveness of gold compounds in the treatment of rheumatoid arthritis, but more recently also because of the growing incidence of hypersensitivity induced by it which is expressed in cutaneous and mucosal reactions. This review discusses dermatotoxicity associated with gold. In some countries gold has moved into second place as allergen, following nickel. Such recognition is mainly due to improved diagnostic methods and to its inclusion in routine dermal patch testing. Some unconventional manifestations of hypersensitivity are associated with use patterns which involve intimate contact with the metal as a component of jewelry. In-depth analysis of the growing number of cases of allergy has revealed various immunological idiosyncrasies as being characteristic of this metal. These include late reactions to challenge, extraordinary persistence of clinical effects, formation of intracutaneous nodules and immunogenic granuloma unresponsive to conventional steroid therapy, the occurrence of eczema at sites distant from the site of contact, and flare-ups of eczema upon systemic provocation with allergen which are characteristic of drug induced allergy. These manifestations demand investigations at the molecular level of the unusual mechanisms of action involved.