Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty-six patients with recalcitrant rheumatoid arthritis entered a trial encompassing a 2-week inpatient period plus a 16-week, randomized double blind, parallel study comparing placebo, 5 mg/m2 and 10 mg/m2 oral weekly methotrexate (MTX). An additional 6 patients, given 20 mg/m2 MTX, contributed to the toxicity, but not the efficacy analysis. All patients had "failed" either gold or D-penicillamine. A linear dose response relationship (placebo vs 5 mg/m2 vs 10 mg/m2) was found for 5 of 11 outcome variables: patient pain and patient global scale, physician global scale, joint tenderness count and activity of daily living scale (p less than 0.05 for each). Gastrointestinal toxicity (p = 0.002), dyspepsia (p less than 0.03) and stomatitis (p less than 0.09) occurred more commonly with MTX, and a general trend, although not significant, was found toward a dose toxicity relationship.
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PMID:Increasing methotrexate effect with increasing dose in the treatment of resistant rheumatoid arthritis. 272 50

One hundred eight-six patients with active rheumatoid arthritis were evaluated in a double-blind, randomized study that compared treatment with sulfasalazine (SSZ) (2 mg/day), gold sodium thiomalate (GST) (50 mg/week), and placebo (PBO). The 37-week course of therapy was completed by 109 patients. While marked improvement was seen in all 3 treatment groups, the only statistically significant differences between SSZ or GST and PBO were in a decreased erythrocyte sedimentation rate and increased grip strength in the right hand. GST is known to be superior to PBO, and the response of the GST-treated group was similar to that seen in other trials. The response of the PBO group, however, was much greater than in other placebo groups we have studied. SSZ was similar in efficacy to injectable gold, but was better tolerated. Because of adverse drug reactions (most commonly, rash, stomatitis, and proteinuria), 41% of patients were withdrawn from the GST treatment. Untoward drug effects (most frequently, rash and gastrointestinal distress) caused 16% of patients to be withdrawn from SSZ therapy.
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PMID:A controlled trial comparing sulfasalazine, gold sodium thiomalate, and placebo in rheumatoid arthritis. 289 44

Seven female patients with classical rheumatoid arthritis (RA), treated successfully with injectable gold salts (Fosfocrisolo ICI, 0.10 g/week, with a serum gold concentration of 200-400 mcg/dl), experienced severe gold side-effects after 3 to 20 months of therapy, requiring their withdrawal from gold despite the good results in both clinical and laboratory findings. Four patients showed mucocutaneous side-effects (2 dermatitis and 2 stomatitis) and three a moderate or severe proteinuria. Renal biopsy was performed in these patients, with a histological picture of membranous glomerulonephritis referable to gold therapy. Remission inducing drug (R.I.D.) therapy being mandatory in patients with a chronic progressive disease, and in view of the previous efficacy of gold salts, the patients were put on oral gold, Auranofin being administered 3 mg b.i.d. Both the mucocutaneous side-effects and the proteinuria ameliorated within 2 to 6 months, and the remission of the disease was maintained. The chemical and pharmacokinetic differences between the above two gold compounds are discussed.
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PMID:Injectable gold dermatitis and proteinuria: retreatment with auranofin. 293 99

Typing for antigens HLA-A,B,C and DR was performed on 165 rheumatoid arthritis patients (14 black, 151 white) who had received gold therapy to determine the relationship between HLA antigens and gold dermatitis, stomatitis, thrombocytopenia, and proteinuria. Dermatitis and stomatitis occurred in both black and white patients. Thrombocytopenia and proteinuria occurred only among the white patients studied. The absence of thrombocytopenia and proteinuria among the black patients was not statistically significant. Antigen HLA-DR7 was uncommon among black and white subjects with dermatitis (0 of 6 blacks, 4 of 48 whites), but this decrease in frequency was not statistically significant. Antigen HLA-DR3 was an important risk factor for thrombocytopenia (relative risk = 11.8, P = .0043) and proteinuria (RR = 5.8, P = .032). These results are consistent with previous studies of HLA-DR3 and gold toxicity. The only black patient with stomatitis possessed the A1B8DR3 phenotype. Future studies should examine whether the same HLA antigen confers risk of different gold toxicities in different racial groups, and whether there are HLA antigens that provide a protective effect.
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PMID:Immunogenetic and racial determinants of gold toxicity in rheumatoid arthritis. 297 88

The association between HLA antigens and adverse drug reactions (ADR), (e.g. proteinuria, haematological abnormalities, stomatitis, diarrhoea and dermatitis) in rheumatoid arthritis (RA) to sodium aurothiomalate (gold) and to D-penicillamine (PA) were studied in 32 patients. Thirty-eight RA patients treated with gold and PA, and with no ADR to these drugs, were used as controls. The frequency of HLA B8 was significantly (p less than 0.05) increased among RA patients with ADR compared to plasma donors. DR3 was also significantly increased (p less than 0.05) in RA patients with haematological ADR compared to plasma donors. Haematological ADR occurred significantly (p less than 0.05) more often in DR3 positive patients (55%) than among DR3 negative RA patients (27%).
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PMID:HLA antigens and adverse drug reactions to sodium aurothiomalate and D-penicillamine in patients with rheumatoid arthritis. 315 29

Twenty-six patients with severe rheumatoid arthritis who had completed a randomized crossover trial of methotrexate elected to continue to receive the drug in a long-term prospective study. At 36 months, 16 patients remained in the study. Over this period of time, significant improvement was noted in the number of painful and swollen joints, physician and patient global assessments, erythrocyte sedimentation rate, and prednisone dose. Adverse reactions occurred in 16 patients (62%), including nausea, alopecia, headache, stomatitis, herpes zoster, and diarrhea. Mild leukopenia (3 patients), thrombocytopenia (3 patients), and elevated transaminase levels (8 patients) resolved with temporary drug discontinuation. No patient withdrew due to drug toxicity. Liver biopsy specimens in 17 patients after 24 months of treatment showed no evidence of fibrosis or cirrhosis. A significant increase in the percentage of T3 and T4 blood cells and increases in lymphocyte proliferation to concanavalin A and purified protein derivative of tuberculin were found after 2 years of therapy. Our findings indicate that methotrexate has remained effective over 36 months of therapy, with acceptable toxicity levels and no evidence of systemic immunosuppression.
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PMID:Long-term prospective trial of low-dose methotrexate in rheumatoid arthritis. 291 60

Auranofin (triethylphosphine gold), an oral gold preparation, has recently been made available, and along with injectable gold preparations, is of therapeutic value for rheumatoid arthritis. Serious gold toxicity is uncommon, and drug-related deaths rare. Many potential adverse reactions are similar, including dermatitis, stomatitis, thrombocytopenia, leucopenia, and proteinuria, generally with increased incidence in the injectable gold-treated patients. Oral gold is associated with benign lower gastrointestinal side effects, including diarrhoea, loose stools and abdominal cramps that are often dose-related and resolve spontaneously. The incidence of severe reactions such as thrombocytopenia, aplastic anaemia and exfoliative dermatitis is lower with oral gold than injectable preparations, and contributes to a superior risk-benefit ratio. The treatment of gold toxicity depends on the type and extent of organ involvement.
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PMID:Adverse reactions with oral and parenteral gold preparations. 329 22

Methotrexate, 7.5-25.0 mg, was taken in a single weekly dose by 101 patients with chronic rheumatoid arthritis. In the course of treatment there was significant improvement in pain and mobility, as well as in the number of inflamed joints, strength of hand-grip (both hands), and use of steroids. There was a significant fall in erythrocyte sedimentation rate, and haemoglobin content rose significantly. Improvement occurred in 85% of patients; within this group 30% had a remission during treatment. There were 7% non-responders. Side effects were frequent: gastrointestinal symptoms in about 50%, loss of hair and stomatitis in 10-20%. In nine patients methotrexate had to be discontinued because of side effects, but in six of them the drug was taken again later on. Transaminases increased in 50% of patients. No clear-cut histological changes were found in the liver. It is concluded that low-dose methotrexate is effective in the long-term treatment of chronic rheumatoid arthritis.
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PMID:[Treatment of chronic polyarthritis with low-dose methotrexate]. 337 Dec 11

The therapeutic effect of low-dose MTX-treatment (10-25 mg/week) in active rheumatoid arthritis can be demonstrated by an improvement in clinical and laboratory parameters of disease activity already after 4-6 weeks. The mode of action is not fully understood. Direct anti-inflammatory effects seem to be more important than the weak immunosuppressive properties. Methotrexate treatment is indicated in all very active cases of rheumatoid arthritis, which do not respond to, or do not tolerate, conventional slow-acting antirheumatic drugs. In severe, rapidly progressing diseases MTX can be given without waiting for the effect of other disease modifying drugs. MTX is administered once a week i.v., i.m. or in one oral dose before breakfast. Absorption is reduced by food. The initial weekly dose is 15-25 mg and can be reduced to a minimum of 10 mg (7.5 mg) according to the clinical effect. A combination with antimalarials or gold salts is possible. The prescription of MTX is contraindicated in cases of renal function disturbances, active liver disease, bone marrow disturbances, active infectious diseases, pregnancy and excessive alcohol consumption. The most common side-effects are nausea and vomiting, stomatitis, transient elevations of transaminases. Rare conditions are leucopenia, thrombocytopenia and lung infiltrations. The side-effects are dose-related and disappear with dose reduction. They can be avoided by administering leucovorin 12 hours after giving MTX. Before starting the treatment total blood count with differential count and platelet count, serum creatinine and liver enzymes should be done. These laboratory studies have to be repeated every week for the first month, every two weeks up to the third month and every 1-2 months thereafter. When contraindications are considered and regular controls are made methotrexate is better tolerated than other cytotoxic agents. The rate of withdrawals is lower than with gold-treatment. In low-dose MTX-treatment drug interactions do not play a major role with normal renal function. Concomitant application of nonsteroidal antirheumatic drugs can delay MTX elimination and increase toxicity. We therefore avoid giving these drugs on the day of MTX-administration as far as possible.
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PMID:[Treatment with low-dose methotrexate in chronic polyarthritis. Review of the literature]. 354 54

The efficacy and acceptability of low dose weekly methotrexate therapy in rheumatoid arthritis was reviewed in 587 patients in open and randomized trials. Gastrointestinal toxicity was reported most frequently. Bone marrow suppression, stomatitis, alopecia, headaches, and fever also occurred. A review of these adverse reactions, as well as of the effects of this drug on the reproductive, renal, and pulmonary systems, is discussed.
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PMID:Toxicity of low dose methotrexate in rheumatoid arthritis. 391 75


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