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)

Currently available techniques do not enable the clinician to identify which patients with rheumatoid arthritis will respond favorably to chrysotherapy or to predict which patients will develop gold-related complications. Gold concentrations are similar in blood, urine, feces, skin, hair and nails in gold-responders and non-responders, and in gold-toxic and non-toxic patients. However, gold toxicity is a function of dosage schedule; higher than conventional doses increase the prevalence and severity of adverse reactions. Preliminary observations suggest that the frequency of common side-effects (e.g. dermatitis, stomatitis, proteinuria) from oral gold (auranofin) is less than that incurred with intramuscular gold prepartions. The possible genetic predisposition to develop gold toxicity is under investigation.
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PMID:Gold compounds in rheumatoid arthritis: clinical-pharmacokinetic correlates. 11 49

Diaziquone (AZQ), a synthetic quinone with demonstrated activity against acute nonlymphocytic leukemia (ANLL), primary CNS tumors, and non-Hodgkin's lymphoma (NHL), is virtually devoid of nonhematopoietic toxicity at conventional doses. As a prelude to its inclusion into bone marrow transplant (BMT) preparative regimens, a phase I study of high-dose AZQ with autologous BMT (ABMT) was performed. Patients with refractory solid tumors and lymphomas were treated with a single 24-hour infusion of AZQ at 50 to 355 mg/m2 in dose escalations of 20%. Fifty-six patients received 69 courses. Those receiving greater than 60 mg/m2 had nadir granulocyte and platelet counts less than 500/microL and 20,000/microL, respectively. Nausea, vomiting, stomatitis, and diarrhea were mild, transient, and not dose-related. Transient minimal elevations of liver function tests were seen in five patients and were also not dose-related. The maximally tolerated dose (MTD) of high-dose AZQ was found to be 245 mg/m2, with nephrotoxicity being dose-limiting. Significant azotemia was seen in four of 12 patients treated at 295 and 355 mg/m2, including fatal anuric renal failure in three of these patients. Reversible proteinuria also occurred in 24 of 26 courses above 150 mg/m2, including nephrotic range proteinuria in eight courses, all at doses of 205 to 355 mg/m2. The proteinuria was also associated with multiple proximal tubular defects including generalized aminoaciduria and proximal renal tubular acidosis. There were six early deaths including two of early renal failure (295 and 355 mg/m2), two of sepsis (205 and 245 mg/m2), one of a pulmonary embolus (85 mg/m2), and one of progressive disease (60 mg/m2). Of 50 patients who were assessable for response, there were seven responses including two of 10 with primary CNS tumors, one of 12 with malignant melanoma, one of five with non-small-cell lung carcinoma, two of two with breast carcinoma, and one of one with ovarian carcinoma. Because of its activity in ANLL and NHL and its unique toxicity spectrum, high-dose AZQ may improve the efficacy of current BMT preparative regimens without significantly increasing their nonhematopoietic toxicity.
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PMID:A phase I trial of high-dose diaziquone and autologous bone marrow transplantation: an Illinois Cancer Council study. 207 48

One hundred and forty patients with classic or definite rheumatoid polyarthritis were treated with N2 mercapto-propionly-glycine: thiopronine (Acadione) at an average dose of 1 g per day over a mean duration of 11.7 months + 10.7 months. The retrospective study of these cases, followed between 1980 and 1988 by the same medical team, permits to evaluate the long-term tolerance of the product. Adverse reaction, always subsiding were observed in 55 p. cent of the patients, requiring discontinuation of the treatment in 40 p. cent of the cases. These side effects occur in 3/4 of the cases, during the first 6 months of the treatment. The intolerance mainly affect skin and mucosae: 46 cases (32.8 p. cent) resulting in 32 instances (22.8 p. cent) discontinuation of the treatment because of stomatitis, pruritus, various types of erythema, pemphigus (1 case). Fourteen patients presented a renal failure (10 p. cent) requiring in 8 instances (5.7 p. cent) discontinuation of the thiopronine because of nephrotic syndrome (3 case) and proteinuria (5 cases). Haematological disorders were observed in 13 instances (9.2 p. cent), justifying, in 10 instances (7.1 p. cent) discontinuation of the treatment because of thrombopenia or leucothrombopenia. The other side effects observed are the following: digestive disorders 15 cases (10.7 p. cent) requiring discontinuation of the treatment in 3 instances (2.1 p. cent), agueusia in 6 instances (4.2 p. cent) requiring discontinuation of the treatment in one case; miscellaneous disorders 13.5 p. cent for which the responsibility of thiopronine is not precisely established (especially hepatic cholostasis, muscle disorders), requiring discontinuation the the treatment in 1.4 p. cent of the cases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Long-term tolerability of tiopronin (Acadione) in the treatment of rheumatoid arthritis. Apropos of 140 personal cases]. 213 12

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

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

For over 50 years, gold therapy has played an important role in the treatment of rheumatoid arthritis. Since 1932, many clinicians and investigators have confirmed the beneficial effects of the water-soluble gold salts, aurothioglucose and gold sodium thiomalate. Gold therapy is indicated for patients with active disease who are not responsive to conservative therapy. To minimize patient risks, contraindications must be considered, and careful clinical and laboratory monitoring must be performed under close supervision by the physician during therapy. Side effects may include vasomotor reactions, dermatitis, stomatitis, leukopenia, proteinuria, nephrosis, and thrombocytopenia. During therapy, one of six patients may have an adverse reaction requiring suspension or termination of therapy. Of the five tolerating gold, one will not benefit, three may have marked improvement, and one may have a remission. The usual recommended dosage schedule is intramuscular injection of 25 to 50 mg of gold salt at weekly intervals until a total of 1,000 mg has been achieved. At this level, gold injections may be spaced biweekly, triweekly, and then monthly for an indefinite period.
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PMID:Parenteral gold in the treatment of rheumatoid arthritis. 622 81

A phase I-II study of KW2083, an analog of mitomycin C (MMC) was performed in a total of 22 patients. KW2083 was escalated by single intravenous administration of 40, 50, 60, 70, and 80 mg/m2 doses. Treatments were repeated every 4-6 weeks unless unacceptable toxicities occurred. The median times taken to reach nadir for each dose level were 9-12 days for leukocytes and 7-13 days for platelets respectively. The median times taken for recovery were 8-22 days for leukopenia and 10-37 days for thrombocytopenia. Variable and non-predictable hematological toxicity was observed in some cases. Biphasic hematological toxicity was observed in 4 courses. Acute toxicity occurred in 17 courses for 11 patients and consisted of nausea (44%), vomiting (13%), diarrhea (2.7%) and stomatitis (2.7%). Nephrotoxicity (elevation of BUN, 8.1% and proteinuria, 5.4%) occurred in 3 patients who had no previous impairment of renal function. Alopecia (8.1%) was also observed. Marked elevations of hepatic enzymes were noted in one patient who developed acute fulminant hepatitis with the second dose of KW2083. Objective response was observed in one of 20 evaluable patients. From this preliminary study, the maximum tolerable dose is 70 mg/m2 and the optimal dose of KW2083 was determined to be 50 mg/m2 at 6-week intervals. KW2083 has been introduced as an MMC analog of potential interest. However, hematological and non of hematological toxicities are very similar to those of MMC and does not appear that KW2083 will supersede MMC.
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PMID:[Phase I-II study of 7-N-(P-hydroxyphenyl)-mitomycin C (KW2083, M83)]. 647 44


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