Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A phase I/II trial of the anti-CD4 monoclonal antibody (mAb) was undertaken in seven rheumatoid arthritis patients in order, (1) to investigate changes in clinical symptoms and possible side effects, and (2) to study the pharmacokinetics and to determine the dose required to achieve saturation of antibody binding sites on blood leucocytes. BL4mAb is a murine IgG2a which binds to the group 2B epitope of the V1 N terminal domain of the CD4 molecule. It inhibits syncitium formation by human immunodeficiency virus-infected cells. BL4 was administered by one hour-long intravenous infusion each day, for 10 days. Doses were steadily increased from 20 mg/d to 40 mg/d in the first three patients (group I) in an attempt to reach a serum antibody residual level sufficient to saturate CD4+ circulating cells. The three other patients (group II) received a dose of 40 mg/d during 10 consecutive days. One patient who presented chills and mild fever during the first BL4 infusion was not included in the analysis. No clinical side effects were observed in the six other BL4-treated patients. Clinical parameters of disease activity were improved within the first 14 days. Clinical improvement was still significant at day 30 in five patients, but at day 60, only the Ritchie index was still below pretreatment levels. Delayed type hypersensitivity reactions decreased in the three patients who exhibited positive reactions before BL4 administration. A transient drop in peripheral blood CD4+ lymphocyte counts occurred during each infusion in the first days of treatment. Pre-infusion CD4+ lymphocyte counts were moderately decreased within the first 8 days, but rose to pretreatment levels 3 days after the last infusion. BL4 residual levels in serum steadily increased to reach 8.0 micrograms/ml in group I and 9.8 micrograms/ml in group II. Saturation of BL4 binding sites was achieved after 2 days of treatment in all patients of group II but in only one of group I. Four out of six patients produced antibodies against the anti-CD4 mAb. Immunization appeared between days 12 and 50. This study shows that saturation of anti-CD4 mAb binding sites can be achieved by infusions of high doses (40 mg/d) of BL4 without clinical side effects. The results would encourage further placebo-controlled trials, since no definite conclusion can be drawn from the present study as regards clinical efficacy.
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PMID:Immunological effects of high dose administration of anti-CD4 antibody in rheumatoid arthritis patients. 177 12

The effect of treatment with a monoclonal antibody against the CD4 antigen present on T helper cells was studied in 10 patients with severe intractable rheumatoid arthritis. In an open trial, monoclonal antibody 16H5 was infused at a dosage of 0.3 mg/kg of body weight on 7 consecutive days. Studies of the kinetics demonstrated a drastic depletion of CD4+ cells, to as low as 25 cells/microliters, 1 hour after the first infusion. The subsequent recovery of the CD4+ cell numbers 24 hours after infusion did not reach initial levels, and after the full 7-day treatment cycle there was a significant reduction of the number of CD4+ cells (mean +/- SD 51 +/- 28%; P less than 0.02). There was a reduced or even inverse CD4:CD8 ratio, which generally persisted 3-4 weeks. Lymphocyte transformation assays demonstrated significantly reduced reactivity in 5 of the 9 patients who completed the 7-day course, whereas 4 individuals exhibited an unexpected elevation in the T cell response to mitogens and common antigens. Parallel laboratory studies showed a significant decrease in the erythrocyte sedimentation rate (P less than 0.05), rheumatoid factor titer (P less than 0.04), and total immunoglobulin values (P less than 0.01), as well as a reduction in C-reactive protein levels, in 7 of the 9 patients. Clinically, there was a significant reduction in the Ritchie articular index (P less than 0.05) and in the number of swollen joints (P less than 0.04). Adverse effects were urticaria in 2 patients, which led to withdrawal of therapy in 1 of them, and chills with fever, suggestive of a lymphokine release syndrome, in another 2 patients. Only low levels of human anti-mouse immunoglobulin antibodies developed (not exceeding 1.7 mg/liter). It was therefore possible to repeat the treatment cycle, achieving still better efficacy, in 4 of the patients (reductions in the Ritchie index and the number of swollen joints P less than 0.02). Our findings indicate that treatment with monoclonal antibodies against the CD4 antigen leads to immunomodulation which results in clinical benefits, at least during initial observation periods (up to 6 months postinfusion). However, it remains to be determined whether long-term remission can be induced with this therapeutic approach. The use of immunosuppressive therapies or repeated antibody treatments will have to be considered.
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PMID:Treatment of rheumatoid arthritis with an anti-CD4 monoclonal antibody. 199 9

Within one year three of 25 patients with rheumatoid arthritis treated with azathioprine 100 mg daily developed the following adverse reactions less than two weeks after starting treatment: patient one showed fever with chills, rash, and severe liver function abnormalities suggestive of cholestasis; the second patient had fever, nausea, diarrhoea, and moderately raised liver enzymes; the third patient showed very high fever and severe chills. In two patients the drug was rechallenged, with more rapidly arising and more severe symptoms. In one case raised liver enzymes persisted until seven months after discontinuation of azathioprine. Hypersensitivity reactions and hepatotoxicity of azathioprine are discussed.
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PMID:Azathioprine induced fever, chills, rash, and hepatotoxicity in rheumatoid arthritis. 213 7

Septic arthritis is a serious and sometimes fatal complication of rheumatoid arthritis. We have examined the clinical characteristics of 16 patients with infectious arthritis seen during an eight-year period. This represented 0.5% of all admissions to our hospital for patients with rheumatoid arthritis. Although rheumatoid arthritis is considered a predisposing factor for joint sepsis, 15 of our patients had other conditions that most likely increased their susceptibility to infection. Many patients lacked distinctive features of joint sepsis (fever, chills) and only one half had leukocytosis. Six had polyarticular complaints despite documented monarthric sepsis. Delay in diagnosis of joint infection and persistent effusions of the infected joints portended a poor prognosis.
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PMID:Infection versus disease activity in rheumatoid arthritis: eight years' experience. 376 20

Four patients whose rheumatoid arthritis (RA) was complicated by staphylococcal arthritis were identified. All patients had active, long-standing disease with destructive changes. Affected joints included hip (two patients), knee (one patient), and shoulder (one patient). Pain and loss of motion in the affected joint were prominent, but toxic features of pyogenic infections--hectic fever, chills, sweats, local warmth, or erythema--were conspicuously absent. Two patients had moderate fever and three patients had mild leukocytosis. No patient was leukopenic. When present, fever was attributed to infected decubiti or urinary tract infection and treated with antibiotics. Therapy with corticosteroids and nonsteroidal antiinflammatory drugs (NSAIDs) probably masked symptoms and delayed the correct diagnosis. Purulent synovial effusions were discovered serendipitously--during arthrography (knee), attempted Girdlestone procedure (hip), and aspiration prior to steroid injection (shoulder). Sepsis was included in the preoperative diagnoses only once (hip). Prior instrumentation (aspiration or injection) of the affected joint was not a feature in any patients, although one patient had undergone insertion of a knee prosthesis one year prior to sepsis. Infectious organisms were Staphylococcus aureus in three patients and Staphylococcus epidermidis in one. Severe sequelae ensued in three of four patients: death from recurrent sepsis (one patient), loss of prosthesis leading to knee arthrodesis (one patient), and protracted sepsis with additional pyarthrosis (one patient). The only patient to regain preseptic joint function (shoulder) had not been on long-standing corticosteroids. Pyarthrosis must be considered in RA patients with unusually painful or stiff joints even in the absence of toxic symptoms.
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PMID:Unrecognized staphylococcal pyarthrosis with rheumatoid arthritis. 408 87

T lymphocytes play an important role in the pathogenesis of rheumatoid arthritis (RA). Murine monoclonal antibody OKT-3 (IgG2a), known to be specific for T lymphocyte 20 kD glycoprotein CD3 receptor was labelled with 5 mCi 99Tcm and given intravenously (i.v.) to seven RA and two psoriatic arthritis patients following informed consent to identify inflamed synovium. Anterior and posterior whole body scans and specific regional imaging was commenced 20 min later. At 1 h, approximately 20% of 99Tcm was associated with the lymphocytes. In these patients, all 41 asymptomatic joints and 43 joints with mild pain or minimal tenderness had normal scans. All 34 joints with moderate to severe pain had moderate to marked uptake of radioactivity. Two patients experienced shaking chills for 20-30 min within an hour of 99Tcm-OKT-3 infusion. These results suggest that 99Tcm-OKT-3 imaging serves as an objective surrogate for joint inflammation and could be useful as a measurement of therapeutic effectiveness in RA and other diseases with inflamed synovium. The side effect profile may limit the utility of 99Tcm-OKT-3 but other forms of antibodies directed toward lymphocyte subsets may be useful.
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PMID:Imaging rheumatic joint diseases with anti-T lymphocyte antibody OKT-3. 783 46

We described a case of rheumatoid arthritis (RA) with selective IgA deficiency. A 69 year-old female with RA was admitted because of gall bladder cancer, and also had selective IgA deficiency which serum IgA level was less than 5.0 mg/dl, and IgA 1 and IgA 2 subclasses were not detected. Prior to the operation, she was given red cell compatible blood transfusion because of severe anemia. After 30 min of transfusion, she developed chill, nausea, vomiting and hypotension. These anaphylactic reactions might be induced by the presence of anti-IgA antibody, since the level of this antibody titers in her serum was elevated, assessed by the methods of ELISA and Western blotting. Although a case of RA associated with selective IgA deficiency, and also with elevated serum anti-IgA antibody level is extremely uncommon, attention should be paid to the presence of anti-IgA antibody in patients with selective IgA deficiency to avoid any unexpected anaphylactic reactions.
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PMID:[A case report of selective IgA deficiency in rheumatoid arthritis and anti-IgA antibody induced anaphylactic transfusion]. 985 51

Infliximab is a chimeric anti-tumour necrosis factor-alpha monoclonal antibody that has been studied for the treatment of Crohn's disease and rheumatoid arthritis. In several placebo controlled, randomized clinical trials and open trials, 771 patients have been given infliximab (a further 192 received placebo). Follow-up for safety has included the time of study (12 weeks after the last infusion), plus three additional years. Acute infusion reactions (headache, fever, chills, urticaria, chest pain) were seen in 17% of patients receiving infliximab compared with 7% of those receiving placebo. While infections were reported more frequently overall in the patients given infliximab (26% over 27 weeks of follow-up versus 16% of placebo-treated patients over 20 weeks of follow-up), there was no increased risk of serious infections. There was no difference in the overall mortality rate between the groups. While low titres of autoantibodies developed in less than 10% of patients, drug-induced lupus was seen in less than 1%, with these cases resolving upon discontinuation of the drug. Overall, infliximab showed an acceptable safety profile.
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PMID:Long term safety of infliximab. 1102 58

INFLIXIMAB: Is a chimeric antitumour necrosis factor-alpha monoclonal antibody that has been studied for the treatment of Crohn's disease and rheumatoid arthritis. A LONG TERM SAFETY: In several placebo controlled, randomized clinical trials and open trials, 771 patients have been given infliximab (a further 192 received placebo). Follow-up for safety has included the time of study (12 weeks after the last infusion), plus 3 additional years. GENERAL TOLERANCE: Acute infusion reactions (headache, fever, chills, urticaria, chest pain) were seen in 17% of patients receiving infliximab compared with 7% of those receiving placebo. While infections were reported more frequently overall in the patients given infliximab (26% over 27 weeks of follow-up versus 16% of placebo-treated patients over 20 weeks of follow-up), there was no increased risk of serious infections. There was no difference in the overall mortality rate between the groups. AT THE POINT OF VIEW IMMUNOLOGIC: While low titres of autoantibodies developed in less than 10% of patients, drug-induced lupus was seen in less than 1%, with these cases resolving upon discontinuation of the drug. Overall, infliximab showed an acceptable safety profile.
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PMID:[Treatment of inflammatory diseases: safety of long-term use of infliximab]. 1131 23

Quinine sulfate, which has been available for many years, has not been implicated definitively in the development of pulmonary toxicity. A variety of adverse effects, however, have been reported with quinine administration. A 45-year-old woman with longstanding rheumatoid arthritis experienced wheezing, severe anxiety, breathlessness, cough, orthopnea, mild fever, chills, and pleuritic chest discomfort after taking a single dose of quinine for nocturnal leg cramps. Radiographic imaging demonstrated diffuse, bilateral pulmonary infiltrates suggestive of pulmonary edema. No cause other than acute quinine ingestion could be identified despite thorough cardiac and infectious disease evaluations. Clinicians should be aware of a possible association between quinine sulfate and pulmonary toxicity.
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PMID:Transient pulmonary infiltrates possibly induced by quinine sulfate. 1206 69


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