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ID PMID Title PublicationDate abstract
11387072 Steroid Injection of the Appendicular Skeleton and Sacroiliac Joints. 1997 Steroid joint injections may be effective in painful joints due to degenerative disease and posttraumatic changes, as well as rheumatoid arthritis and seronegative spondylarthropathy. Fluoroscopic guidance may be necessary for deep (sacroiliac, hip, and shoulder) or small (wrist, hand, and foot) joints. Detailed technique of the steroid injection is given, especially for the sacroiliac joint.
11220203 [Psoriasis complicated with severe mutilating psoriatic osteoarthropathy. Clinical case an 2000 Sep Aim of this paper is to discuss, on the basis of an extensive critical review of the recent literature, the case of a 56-yr-old male patient who suffered from cutaneous psoriasis and psoriatic arthritis mutilans (PA) (polyarticular, symmetric, destruent and erosive) with involvement of the hands, feet and spine, associated with android obesity and mild type 2 diabetes mellitus. HLA typing of the patient showed the HLA-A3-Ax, B14-B63 and Cw4-Cw6 haplotypes, some of which are associated or correlated with susceptibility to PA. Cutaneous psoriasis is a chronic inflammatory dermatitis, with onset at any age and affecting approximately 2% of the western populations. In 5-7% of patients, it is associated with articular manifestations or true arthritis. PA is a chronic, inflammatory, seronegative arthropathy which may develop in some psoriasis patients, may involve peripheral and axial (spondarthritis) joints and may lead to severe joint destruction. Genetic, immunologic and environmental (i.e., infectious agents or trauma) factors seem to play an important role in the onset and clinical appearance of PA. Although PA is a clinically monomorphic disease, it may show different heterogenous subgroups with differences in their etiopathogenesis. When PA is suspected, it is mandatory to analyze carefully the patient's familiar history, search attentively for the specific skin features, exclude a septic arthritis (especially if the involvement is monoarticular) and, in the cases of fulminant disease, consider always the possible coexistence of an acquired immunodeficiency syndrome. PA can occasionally be an aggressive, disfigurating and disabling disease and the treatment (incisive and precocious) should be similar to that for rheumatoid arthritis. At present, a definitive therapy does not yet exist, but the majority of PA patients can lead a fairly normal life and they do not show increased mortality rates (excluding the severe cases of erythrodermic or pustulosis psoriasis). However, as a result of the various problems of occupation and morbidity it causes, PA is a disease with great social involvement.
12973435 The role of cytokines in rheumatoid arthritis: inhibition of cytokines in therapeutic tria 1999 Apr Although the precise role(s) of cytokines in rheumatoid arthritis (RA) is still being investigated, increasing evidence implicates interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha as contributing importantly to the inflammatory, and perhaps destructive manifestations of the disease. Several natural endogenous inhibitors of IL-1 and TNF-alpha have been identified; these include interleukin-1 receptor antagonist (IL-1RA), soluble IL-1 receptors (sIL-1R), and soluble TNF-alpha receptors (sTNFR). Although increased levels of these natural inhibitors occur in sera and at sites of inflammation in patients with RA, there is an excess of IL-1 and TNF-alpha in comparison with their respective natural inhibitors that favors the proinflammatory actions of these cytokines. Therefore, a potential therapeutic maneuver for treating RA is to neutralize these implicated cytokines. Biologic agents aimed at inhibiting the proinflammatory activities of these cytokines thus far have included cytokine receptor antagonists, anticytokine monoclonal antibodies (MAbs), fusion molecules consisting of soluble cytokine receptors combined with human fusion protein (Fc) constructs or polyethylene glycol (PEG), and counterregulatory cytokines which oppose actions of the target cytokine (e.g., IL-10, IL-4 and IL-11). Inhibitors of the processing and synthesis of IL-1 and TNF-alpha are also under development. The encouraging clinical results observed in short-term trials of TNF-alpha and IL-1 inhibitors using sTNFR:Fc fusion proteins, anti-TNF MAbs and recombinant human IL-1 receptor antagonist (rhuIL-1RA) clearly warrant further studies not only to determine whether these agents are capable of modifying the destructive component of the disease, but also whether they can be administered safely for long periods. Pivotal trials with these agents have potential therapeutic applicability to other autoimmune and inflammatory disorders.
11720158 The presentation, aetiology, management and outcome of optic neuritis in an Asian populati 2001 Oct PURPOSE: To analyse the presentation, aetiology, management and outcome of patients with optic neuritis (ON) in Singapore. METHODS: This was a retrospective study involving consecutive patients with ON presentng at the Singapore National Eye Centre between January 1997 and May 1999. The presenting features, investigatons, treatment and visual outcome after 6 months were studied. RESULTS: A total of 31 patents (39 eyes) presented with ON during this period, 17 of whom had anterior ON. No aetiology was found in 26 patients (83.9%), two patients (6.5%) had multiple sclerosis, one had active syphilis, one had rheumatoid arthritis and another had pan-sinusitis. Seventeen patients (54.8%) were treated with intravenous methyl-prednisolone followed by oral prednisolone. Within the follow-up period 26 of 31 eyes (83.9%) wth idiopathic ON attained visual acuity of 6/12 or better with 12 (38.7%) recovering to 6/6 or better and only one eye ending with less than 6/60 visual acuity. The one patient with syphilis recovered 6/6 visual acuity bilaterally. Both patients with multiple sclerosis also had good visual recovery at 6 months. The visual outcome in those cases of ON associated with rheumatoid arthritis and pan-sinusitis was poor with visual acuity of less than 6/60 at 6 months follow up in each instance. CONCLUSION: The majority of the cases of ON in this study were idiopathic. There was a low association with multiple sclerosis. Most patients had good visual recovery within 6 months.
11137896 Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a marker of oxidative stress in rheumatoid 2000 Nov Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), as a measure of oxidative stress, was measured before and after 12 weeks of progressive resistance strength training in 8 healthy elderly (65-80 yr) and eight healthy young (22-30 yr) men and women, and in eight adults (25-65 yr) with rheumatoid arthritis (RA).Training subjects exercised at 80% of their one-repetition maximum and performed eight repetitions per set, three sets per session, on a twice-weekly basis. 8-OHdG was measured at baseline and follow-up (at least 24 hr after the last exercise session) in the RA and elderly subject groups, and at baseline only in young subjects.Baseline 8-OHdG levels were greater among subjects with RA compared to both healthy young (P < 0.001) and elderly (P < 0.05) subjects. There were no changes in 8-OHdG levels in either RA or elderly subjects as a result of the strength training intervention.These results suggest that subjects with RA have higher levels of oxidative stress than young and elderly healthy individuals. Furthermore, there is no change in oxidative stress, measured by urinary 8-OHdG, in elderly healthy individuals or in subjects with RA after a 12-week strength training intervention.
9809693 Utilization of rheumatology physician services by the elderly. 1998 Oct PURPOSE: To examine rheumatology subspecialty practice patterns, determinants of referral to rheumatologists, and utilization of aspiration and injection procedures in a population-based sample of elderly individuals. SUBJECTS AND METHODS: We obtained Medicare physician claims for all visits to rheumatologists among beneficiaries aged 65 years and older in Colorado, Massachusetts, and Virginia in 1993, and for visits to all providers by patients with coded diagnoses of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We examined variations in visit frequency and aspiration/injection procedures, and we analyzed determinants of referral to a rheumatologist for RA or SLE. RESULTS: In 1 year, 144,797 visits were made to rheumatologists by 38,443 patients in the three states. An inflammatory disorder was coded in 45% of visits and a noninflammatory disorder in 50%. Half of patients with RA were seen three or fewer times in the year. For RA and SLE, African Americans were about 60% as likely to be seen by a rheumatologist as whites. Utilization of rheumatologist services for rheumatoid arthritis and systemic lupus erythematosus was highest in the state (Virginia) with the lowest per capita supply of rheumatologists. Among patients with bursitis, tendinitis, and osteoarthritis, African-American women were more likely to receive an injection or aspiration procedure than whites or African-American men. CONCLUSION: Elderly patients with rheumatologic disorders were seen by specialists less frequently than recommended by a recent rheumatology manpower survey. African-Americans with RA and SLE had fewer rheumatology visits than whites.
17039159 Current medication choices in juvenile rheumatoid arthritis II--update of a survey perform 2001 Oct The documentation of treatments used for Juvenile Rheumatoid Arthritis (JRA) is important to allow for the evaluation of practice patterns for future outcome studies. A survey of nine pediatric rheumatologists was performed between September 1999 and February 2000. Each of the physicians prospectively recorded demographic and treatment information on consecutively sampled JRA patients (n=395). Pauciarticular onset JRA was present in 46%, polyarticular onset JRA in 35%, and systemic onset JRA in 19% of the children. Naproxen was the most frequently prescribed medication (55% of the patients), followed by methotrexate (MTX), which was used in 39% of the patients. Folic acid supplementation (1 mg/day) was provided to 69% of the patients treated with MTX. Etanercept was used in 11% of the children. Eleven percent of the patients received corticosteroids, and 13% of children on corticosteroids took calcium supplements. Uveitis was present in 8% and had a chronic course in 79% of those cases. Although systemic medications were used in 50% of the children with uveitis to control eye inflammation, severe damage to the eyes developed in 30% of them. Fourteen percent of the patients required gastroprotective medications. Compared with findings of a similar survey performed in 1993, there was no significant change in the frequency of use of naproxen, but nabumetone is now more often prescribed, and COX-2 inhibitors have been introduced in the therapy of JRA. Changes among second-line agents used for JRA have also occurred, although there was no change in the frequency of use of MTX or corticosteroids. JRA continues to be a treatment challenge for the practicing pediatric rheumatologist. Patients often show incomplete response to the currently available medications. Therefore, new therapeutic agents need to be evaluated for their use in JRA, and the treatment of JRA associated uveitis especially needs to be improved.
10459546 Mycophenolic acid increases apoptosis, lysosomes and lipid droplets in human lymphoid and 1999 Aug 15 BACKGROUND: Mycophenolic acid (MPA), a selective inhibitor of inosine monophosphate dehydrogenase, is the active agent of the immunosuppressive drug, mycophenolate mofetil (MMF). Previous studies have shown that MPA inhibits DNA synthesis in T and B lymphocytes by blocking de novo guanosine synthesis, and that MPA induces monocyte differentiation. MMF is being used for prevention of organ graft rejection and has also shown efficacy in rheumatoid arthritis trials. This study was designed to determine if apoptosis also plays a role in the immunosuppressive and anti-inflammatory effects of MMF. METHODS: Cultured human T lymphocytic (MOLT-4) and monocytic (THP-1 and U937) cell lines were treated with MPA. Apoptosis, cell viability, DNA content, lipid content, cell volume, and lysosomes were measured by a variety of microscopic, flow cytometric, and biochemical techniques. RESULTS: MPA inhibits proliferation, arrests cell cycle in S phase, and increases apoptosis in all three cell lines. Exogenous guanosine added within 24 hr of MPA treatment, but not later, partially reversed MPA-induced apoptosis in MOLT-4 cells. MPA increased lipid droplets in all three cell lines and increased both cell volumes and numbers of lysosomes in the monocytic cell lines. In both monocytic cell lines, MPA also reduced the number of nuclei containing nucleoli and greatly increased neutral lipids, primarily triacylglycerols, suggesting that these cells were differentiating. CONCLUSIONS: Increased apoptosis and terminal differentiation of both lymphocytes and monocytes may promote the antiproliferative, immunosuppressive, and anti-inflammatory effects of MMF seen clinically in transplantation and rheumatoid arthritis.
9474734 Occipital calvarial bone graft in posterior occipitocervical fusion. 1998 Jan 15 STUDY DESIGN: Dorsal occipitocervical fusion is associated with a high rate of fusion failure and requires an additional surgical site for donor bone graft harvesting. In this series, an autologous occipital calvarial bone graft obtained from the same occipitocervical incision with contoured metal loops was used in 25 adults to achieve craniovertebral stabilization and fusion. OBJECTIVES: To study the use of autologous occipital calvarial bone grafts in occipitocervical fusion. SUMMARY OF BACKGROUND DATA: Cranial bone grafts have been used successfully in craniofacial reconstruction with good long-term results. In the plastic surgery literature, there are claims that membranous bone grafts are superior to endochondral bone grafts in fusions because of decreased resorption. In recent studies, results have shown successful use of calvarial bone in fusing the upper cervical spine in children. The use of autologous occipital bone in posterior occipitocervical fusions avoids many of the problems associated with traditional donor sites and provides a sufficient quantity of good quality bone for the fusion. This is especially true in the fragile rheumatoid arthritis patient with cranial cervical instability. METHOD: Split-thickness, autologous calvarial bone grafts with contoured loop and cable instrumentation were used for posterior occipitocervical stabilization and fusion in 25 patients, most of whom had rheumatoid arthritis. The calvarial bone graft was harvested from the occipital skull, using a microair impactor, and was secured next to the loop construct. After surgery, all patients were immobilized with external orthoses. RESULTS: None of the patients had hardware failure or complications from the occipital graft procurement. In 22 patients, good alignment, stability, and bony fusion were shown on radiographs. CONCLUSIONS: Occipital calvarial bone graft appears to work as well as other autologous corticocancellous bone grafts routinely used in posterior occipitocervical fusions.
9106316 Atlantoaxial dislocation. A follow-up study of surgical results. 1997 Apr 1 STUDY DESIGN: The cases of 47 patients with atlantoaxial dislocation exclusive of rheumatoid arthritis, cerebral palsy, and tumors as causative pathologies were reviewed after surgical treatment, which was performed between 1979 and 1993. OBJECTIVES: To investigate the surgical results of atlantoaxial dislocation itself without any systemic factors affected by rheumatoid arthritis, cerebral palsy, and tumors. METHODS: Neck pain (or occipitalgia) and extent of myelopathy at follow-up evaluation were compared with that present before surgery. The results were classified into four groups: excellent (no pain or recovery rate in myelopathy of more than 50%), good (decreased pain or recovery rate of 25% to 50%), fair (no improvement of pain or recovery rate of zero to 25%), and poor (aggravation of pain or recovery rate less than zero). The average follow-up period was 4 years and 2 months. RESULTS: Of the patients evaluated, 51% were assessed as excellent, 23% as good, 7% as fair, and 19% as poor. Pain relief was achieved in 95% of patients with non myelopathy. Extent of myelopathy, pathology of atlantoaxial dislocation (ligamentous or osseous instability), loss of reduction after surgery, and surgical procedures were recognized as the major factors affecting surgical results. Better surgical results were obtained in mild myelopathy cases (> 10 points in Japan Orthopaedic Association scoring), ligamentous instability, and cases without loss of reduction. The incidence of pseudarthrosis and loss of reduction was low in Brooks' method for atlantoaxial fusion and in Luque's segmental sublaminal wiring method for occipitocervical fusion. CONCLUSION: The best results occurred in patients with no myelopathy, and the worst results occurred in patients with severe myelopathy; therefore, surgery is best indicated for atlantoaxial dislocation with intractable pain or with mild myelopathy. To avoid pseudarthrosis and loss of reduction, a strong fixation method, such as Brooks' or Luque's segmental sublaminal wiring method, should be selected.
9065224 Adaptive responses among Dutch elderly: the impact of eight chronic medical conditions on 1997 Jan OBJECTIVES: This study analyzed the impact of eight common chronic medical conditions on functional, social, and affective domains of health-related quality of life among community-based Dutch elderly (n = 5279). METHODS: Health-related quality of life was measured with six domains of the MOS Short-Form General Health Survey. The impact of the selected chronic conditions on health-related quality of life was analyzed by means of Student's t tests, analyses of variance, and multiple regression analyses. RESULTS: Compared with other domains of health-related quality of life, mental health was the least affected by chronic medical conditions. Back problems and rheumatoid arthritis/other joint complaints accounted for relatively high proportions of the variance in health-related quality of life (from 35.5% to 68.3%), except for health perceptions (22.6%), indicating that health-related quality of life is most affected by these two conditions. CONCLUSIONS: Subjective well-being is by far the domain least affected by chronic medical conditions, while physical functioning and health perceptions are most affected. Back problems and rheumatoid arthritis/other joint complaints affect health-related quality of life strongly.
9609141 Sterile neutrophilic folliculitis with perifollicular vasculopathy: a distinctive cutaneou 1998 Apr The authors prospectively encountered skin biopsies from 20 patients which demonstrated a neutrophilic or suppurative and granulomatous folliculitis accompanied by a folliculocentric neutrophilic vascular reaction of Sweet's-like or leukocytoclastic vasculitis subtypes. While in each case the histomorphology raised diagnostic consideration of bacterial folliculitis, patients frequently expressed systemic complaints such as arthritis, fever, and malaise, and special stains for micro-organisms were negative. Among the clinical presentations were folliculitis, vasculitis, acneiform eruptions, vesiculopustular lesions, and erythema nodosum-like lesions, with the legs, arms, and upper back being the most commonly involved sites. Nineteen patients were found to have specific underlying systemic diseases, namely, inflammatory bowel disease, Reiter's disease, Behçet's disease, hepatitis B, connective tissue disease including mixed connective tissue disease and rheumatoid arthritis, scrofuloderma, and hematologic dyscrasias. The other patient had antecedent bacterial sinusitis in the setting of atopy. The folliculocentric nature of these lesions may reflect preferential processing of antigens through the hair follicle and/or homology between bacterial and follicular heat shock proteins in the susceptible host, namely, one who responds excessively to exogenous antigenic triggers. Folliculitis with folliculocentric vasculopathy may be a clue to underlying systemic disease and/or an extracutaneous infection. Certain light microscopic features in concert with the clinical presentation may distinguish such cases from conventional infectious folliculitis.
9770519 Synthetic amino acid copolymers that bind to HLA-DR proteins and inhibit type II collagen- 1998 Oct 13 Copolymer 1 [poly(Y,E,A,K)] is a random synthetic amino acid copolymer of L-tyrosine, L-glutamic acid, L-alanine, and L-lysine that is effective both in suppression of experimental allergic encephalomyelitis and in the treatment of relapsing forms of multiple sclerosis. Copolymer 1 binds promiscuously and very efficiently to purified HLA-DR molecules within the peptide-binding groove. In the present study, YEAK and YEAK-related copolymers and type II collagen (CII) peptide 261-273, a candidate autoantigen in rheumatoid arthritis (RA), competed for binding to RA-associated HLA-DR molecules encoded by DRB1*0101 and DRB1*0401. Moreover, these copolymers (particularly YEAK, YAK, and YEK) inhibited the response of DR1- and DR4-restricted T cell clones to the CII epitope 261-273 by >50%. This direct evidence both for competitive interactions of these copolymers and CII peptide with RA-associated HLA-DR molecules and for inhibition of CII-specific T cell responses suggests that these compounds should be evaluated in animal models for rheumatoid arthritis.
9536388 Cold-induced coronary Raynaud's phenomenon in patients with systemic sclerosis. 1998 Mar OBJECTIVE: Cardiac involvement with myocardial-band necrosis is common in systemic sclerosis. One possible explanation is that an underlying vasomotor abnormality accounts for these histologic findings. To shed light on this issue we investigated the existence of "myocardial Raynaud's phenomenon" in such patients. METHODS: We examined 25 patients with systemic sclerosis and 14 patients with systemic lupus erythematosus or rheumatoid arthritis, using cold pressor and dipyridamole-thallium-201 scintigraphy. RESULTS: Twenty-three patients with systemic sclerosis and 13 patients with lupus erythematosus or rheumatoid arthritis had normal perfusion during dipyridamole imaging. Seven scleroderma patients with normal dipyridamole test presented cold-induced transient myocardial ischemia, while none of the control patients had cold-induced ischemia (p = 0.034). All patients with cold-induced ischemic defects presented long-standing Raynaud's phenomenon (> 5 years); of the 14 patients with long-standing Raynaud's phenomenon 7 presented ischemic thallium-201 defects; of the remaining 9 patients with Raynaud's phenomenon of short duration (< 5 years) none presented cold-induced ischemia (p = 0.019). CONCLUSION: Patients with systemic sclerosis and long-standing Raynaud's phenomenon, even in the presence of normal myocardial perfusion during pharmacological vasodilation with dipyridamole, may present cold-induced myocardial ischemia, a functional Raynaud's phenomenon of the heart.
15989561 Leflunomide and malononitriloamides. 1997 Jan Leflunomide is a new immunomodulatory drug effective in experimental models of autoimmune diseases and allo- or xenotransplantation. In a Phase II clinical trial leflunomide has shown high tolerability and efficacy in patients with advanced rheumatoid arthritis. The immunomodulatory activity of leflunomide is attributed to its primary metabolite, A77 1726, a malononitriloamide. The in vitro and in vivo mechanisms of action of this class of compounds remain to be completely defined. A77 1726 and several malononitriloamide analogues inhibit T- and B-cell proliferation, suppress immunoglobulin production, and interfere with cell adhesion. While no one central molecular mechanism of action has been proposed to explain all the effects of the malononitriloamides, inhibition of de novo pyrimidine biosynthesis and inhibition of cytokine- and growth factor-receptor associated tyrosine kinase activity are leading hypotheses for the effects of A77 1726 on T- and B-cell proliferation and function. Leflunomide is effective when administered at daily doses of 10 and 25 mg to patients with active rheumatoid arthritis. The improved efficacy at the 25 mg dose is associated with a higher incidence of adverse effects (gastrointestinal symptoms, weight loss, allergic reactions, skin rash, and reversible alopecia). Due to the long plasma half-life of A77 1726 (11-16 days), loading doses are required to achieve steady-state concentrations. Phase III randomised, placebo-controlled trials using daily doses of 10 or 20 mg are underway in the US and Europe to confirm and extend the results of the Phase II study. Malononitriloamide analogues of A77 1726 are being evaluated for immunosuppressive efficacy in preclinical models of transplantation, because these compounds have a shorter half-life in animals than A77 1726. If these analogues show efficacies similar to leflunomide in these models and have shorter half-lives than A77 1726 in Phase I trials, the preclinical and Phase I data will be used to select the analogues for Phase II trials in organ transplant recipients.
11060801 Ongoing trials with matrix metalloproteinase inhibitors. 2000 Sep Excessive or poorly regulated matrix metalloproteinase (MMP) activity has been implicated as a pathogenic factor in a range of diseases where the extracellular matrix is degraded or remodelled. Synthetic, potent, low molecular weight MMP inhibitors (MMPIs) have been developed and, over the past five years, these agents have begun clinical testing in patients with cancer, rheumatoid arthritis, osteoarthritis and acute macular degeneration. The past year has seen a number of disappointments with the halting of clinical trials of Ro 32-3555 in patients with rheumatoid arthritis and of BAY 12-9566 in patients with cancer. There have, however, been some successes with perhaps the clearest indication of efficacy being seen in the results of a Phase III trial of marimastat in patients with advanced gastric cancer. Clinical trials are continuing with marimastat and other MMPIs, including prinomastat, solimastat, BMS 275291, metastat and neovastat. Results from these trials are expected in the next two years and it is likely that clinical trials with MMPIs will begin in patients with other diseases where MMPs are believed to be involved, such as restenosis, cerebral haemorrhage and multiple sclerosis. Future research is likely to focus on the identification of specific MMP targets in different diseases, both in order to improve efficacy and to reduce the musculoskeletal side effect profile that has characterised several of the first generation oral MMPIs.
11037077 A family physician's guide to monitoring methotrexate. 2000 Oct 1 Methotrexate has a long history of use in the treatment of various immunologic diseases, including rheumatoid arthritis and psoriasis. Although the drug is usually prescribed by a subspecialist, a family physician may assume responsibility for monitoring methotrexate therapy. Major toxic effects, such as hepatic, pulmonary, renal and bone marrow abnormalities, require careful monitoring. Minor toxic effects, such as stomatitis, malaise, nausea, diarrhea, headaches and mild alopecia, are common but respond to folate supplementation. Methotrexate is administered once weekly as a single dose or in divided doses given over a 24-hour period. To reduce the incidence of major toxic effects, methotrexate should never be given in daily doses. Relative contraindications include renal dysfunction, liver disease, active infectious disease and excessive alcohol consumption. Both women and men of reproductive age should use birth control during methotrexate therapy. Potential drug interactions include salicylates and nonsteroidal anti-inflammatory drugs, which are both commonly used in patients with rheumatoid arthritis or psoriasis. A premethotrexate evaluation is important to ensure proper patient selection for this effective but potentially toxic drug.
24383564 Additive combination of actarit and methotrexate in the treatment of refractory rheumatoid 2000 Jun Abstract The objective of this study was to evaluate the efficacy and safety of an additive combination of a disease-modifying antirheumatic drug (DMARD) actarit and low-dose methotrexate (MTX) in patients with active rheumatoid arthritis (RA) unresponsive to MTX. Thirty-four patients with active RA, who had been unsuccessfully treated with MTX for at least 3 months were enrolled on a 24-week course of actarit (300 mg/day) and MTX (2.5-10 mg/week). Disease activity was evaluated by physical global assessments using conventional measures (Japan Rheumatism Association), and the American College of Rheumatology (ACR) criteria of improvements in RA. Thirty-two patients completed this study. No severe adverse drug reactions were seen. Patients whose RA did not respond to MTX alone responded to the combination therapy, with a significant improvement in the duration of morning stiffness, grip strength, swollen joint counts, patient's articular pain score, modified health assessment questionnaire (M-HAQ) score, score of both patient's and physician's global assessments, and C-reactive proteins (CRP). Sixteen patients (50.0%) and 9 patients (31.0%) showed a significant improvement in overall conventional measures, and ACR response criteria, respectively, and 60.0% of RA patients who received MTX for more than 1 year showed improvement in ACR definition. Patients who responded to the combination treatment within the first 12 weeks showed persistent improvement for the remaining part of the 24 week period. Our results indicate that the additive combination of actarit and MTX is safe, and without serious adverse effects, and has an excellent efficacy in patients with active and refractory RA.
11429414 Induction of cellular antioxidative stress genes through heterodimeric transcription facto 2001 Sep 7 Gold(I)-containing compounds have long been used in the treatment of rheumatoid arthritis (RA), but the molecular mechanism of their action has remained largely unknown. In this paper we have demonstrated that gold(I) drugs selectively activate the DNA binding of a heterodimer consisting of the basic-leucine zipper transcription factors Nrf2 and small Maf. Once bound to its recognition DNA sequence termed antioxidant-responsive element or Maf-recognition element, Nrf2/small Maf induces a set of antioxidative stress genes, including heme oxygenase-1 and gamma-glutamylcysteine synthetase, whose products have been demonstrated to contribute to the scavenging of reactive oxygen species and to exhibit anti-inflammatory effects. Our findings suggest that stimulation of antioxidative stress response through activation of Nrf2/small Maf may be a pharmacologically important part of the actions of gold(I) drugs for the treatment of rheumatoid arthritis. Alternatively, activation of Nrf2/small Maf may be a protective response of cells against toxic effects of the drugs.
10628710 Quality of life and health status in pediatric tonsil and adenoid disease. 2000 Jan OBJECTIVE: To assess the baseline global health status and quality of life (QOL) in children with tonsil and adenoid disease. DESIGN: Cross-sectional multicenter survey series. SETTINGS: A tertiary academic pediatric specialty hospital and a tertiary academic hospital in 2 different cities. PATIENTS AND OTHER PARTICIPANTS: Consecutive series of 55 parents of children who were seen for tonsil and adenoid disease. INTERVENTION AND METHOD: Cross-sectional survey of the health status of affected children to assess their QOL and its relationship to tonsil and adenoid disease. MAIN OUTCOME MEASURES: Quality-of-life subscale scores of affected children on the Child Health Questionnaire version PF28 (CHQ-PF28); comparisons of population data from healthy normal children and children with asthma and juvenile rheumatoid arthritis. RESULTS: The overall health status and QOL of children with tonsil and adenoid disease is significantly worse than those of healthy normal children, as demonstrated by lower mean scores on several CHQ-PF28 subscales, including general health, physical functioning, behavior, bodily pain, and parental impact (emotional). In addition, the general health perception of children with tonsil and adenoid disease is similar to the perceptions of children with asthma and juvenile rheumatoid arthritis, but several aspects of health status, as measured by CHQ-PF28 subscale scores, were significantly worse in children with tonsil and adenoid disease. CONCLUSION: The health status impact of tonsil and adenoid disease appears to be quite significant, particularly in aspects related to the parental impact of the child's disease.