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Biomedical subjects

D E Furst

Publications and source records attributed to D E Furst.

At least 127 records · Page 7Linked to original sources
PubMed1992

Lipogranulomas and gold in the liver in rheumatoid arthritis.

Liver biopsies have been performed routinely as part of a protocol to evaluate methotrexate therapy in severe rheumatoid arthritis. All patients in the study had failed standard medical therapy, including gold treatment. Twenty-three of 41 patients (56%) had well-formed lipogranulomas (LGs) in the lobules, compared with an incidence of approximately 5% in our general biopsy population. Twenty-seven of 41 patients (66%) had a unique pigment in their livers. In 20 of these, the pigment was in LGs; in the seven patients with pigment not associated with lobular LG, it was found in lipid droplets in portal triads. The pigment varied from irregular pale brown granules slightly larger than those of hemosiderin, to smaller black round granules. Lipogranuloma-associated pigment of this type is an unusual finding, reminiscent of argyria. There was a variable appearance upon polarization, the black granules at times being strikingly refractile. There was a positive correlation between the prominence of LG and the quantity of pigment. The pigment resembled that described with gold deposition in other tissues. Radiographic microanalysis of both brown and black granules was performed in three cases. Characteristic spectra (energy-dispersive spectroscopy) demonstrated the presence of gold in each case. Silver was not identified. The high incidence of LG may reflect the frequent administration of gold in an oily vehicle. Gold may remain trapped in the liver for a prolonged time. Thus far, we have not detected any adverse effect from the presence of LG-associated gold.

Arthritis, Rheumatoid↗
PubMed1992

Radiographic evidence of disease progression in methotrexate treated and nonmethotrexate disease modifying antirheumatic drug treated rheumatoid arthritis patients: a meta-analysis.

Methotrexate (MTX) has proven to be efficacious in the treatment of rheumatoid (RA), but it remains to be proven whether it can slow disease progression, as determined radiographically, in comparison with other disease modifying antirheumatic drugs (DMARD). We performed a meta-analysis of the available data to answer this question. A literature search, including abstracts, was conducted and inclusion criteria developed (description of patients, accountability of patients, inclusion of a control group of patients, specified radiographic endpoint, and appropriate reading of the radiographs). Publications were scored on a scale of 0 to 5 with a score > or = 3 required for inclusion in the study. For abstracts selected, additional data were obtained directly from the investigators. Data for 353 MTX treated and 205 non-MTX-DMARD treated patients with RA were gathered. Not all publications used the same scoring system, so some assumptions were required to analyze the combined data. Only the erosion score was included since not all publications included a reading of the joint space. All scores were transformed into Sharp scores (Arthritis Rheum 1985;28:1449), including the important contributions of 3 Larsen scored publications. Finally a monthly rate of disease progression was computed. Several comparisons were made. Overall, the rates of disease progression were similar for MTX and non-MTX-DMARD treated patients with RA. The non-MTX-DMARD treated patients with RA were separated into a group treated with gold salts (oral or parenteral) and a group treated with azathioprine with each group compared to the MTX treated patients. MTX had slower rates of disease progression than azathioprine, (rates 0.004 vs 0.012) but not slower rates than gold salts (0.008 vs 0.008). Despite its efficacy, the possible role of MTX in slowing disease progression more than other DMARD, as determined radiographically, appears to be evident only when compared to azathioprine.

Adult↗
PubMed1992

Toxicity of antirheumatic medications in children with juvenile arthritis.

Using patient related examples, the toxicity of nonsteroidal antiinflammatory drugs and disease modifying antirheumatic drugs (DMARD) in juvenile arthritis (JA) is discussed. DMARD combinations are also reviewed. Gastrointestinal side effects are not emphasized. Rather, central nervous system, hepatic, and renal effects are discussed. Ibuprofen is safer than aspirin and has a generally good record. Although data is not excellent and often relies on open studies, hydroxychloroquine is probably the safest DMARD. Methotrexate appears safe, but studies in adults mandate some continued caution in its use in children. Combination DMARD therapy, while used, is dependent on largely open or anecdotal data in adults. The efficacy and toxicity of DMARD combinations are not well understood.

Anti-Inflammatory Agents↗
PubMed1991

Cardiac score. A semiquantitative measure of cardiac involvement that improves prediction of prognosis in systemic sclerosis.

Cardiac involvement, assessed yearly by a semiquantitative cardiac scoring technique (the sum of 2 variables, scored 0 or 1 for left axis deviation, and 0 or 2 for moderate-large pericardial effusion) and outcome at 10 years were evaluated in 90 systemic sclerosis (SSc) patients enrolled in a 3-year prospective drug trial. Higher cardiac scores were associated with decreased survival. The inverse relationship of survival with cardiac score was more significant than the relationship between survival and any of the cardiopulmonary variables individually (P less than 0.0000003). Predicted 6-year survival was 79% in patients with a cardiac score of 0, 51% in those with a score of 1, 15% in those with a score of 2, and 0% in those with a score of 3. We conclude that a simple 2-variable weighted cardiac score, derived from routine electrocardiography and echocardiography, is a useful predictor of survival in patients with SSc, and we propose that the application of this cardiac score be tested in other populations of SSc patients.

Adult↗
PubMed1991

The efficacy and safety of low-dose corticosteroids for rheumatoid arthritis.

Low-dose corticosteroids (defined as less than or equal to 10 mg/d of prednisone or equivalent) are used increasingly for the management of rheumatoid arthritis. They are frequently substituted for nonsteroidal antiinflammatory drugs (NSAIDs), particularly in patients with gastrointestinal or other intolerance to NSAIDs, or as "bridge therapy" while patients await the benefits of delayed-acting, disease-modifying agents. Despite their clinical acceptance, published data concerning efficacy are meager. Adverse effects to low-dose corticosteroids are not so frequent nor so severe as those that occur with higher doses. Nevertheless, alterations in glucose metabolism, cutaneous atrophy, cataracts, and glaucoma are common. Osteoporosis, steroid-myopathy, a steroid-withdrawal syndrome, and dysfunction of the hypothalamic-pituitary-adrenal axis appear in some patients. Osteonecrosis, gastrointestinal, cardiovascular, infectious, or neurological complications probably do not occur. Fetal wastage, prematurity, or congenital malformations have not been proven with this dosage.

Adrenal Cortex Hormones↗
PubMed1990

Rheumatoid arthritis. Practical use of medications.

The treatment of rheumatoid arthritis is undergoing steady change as new medications are approved and new regimens are attempted. Once the diagnosis is ensured, therapy should include appropriate rest, physical and occupational therapy, involvement of the family or a supportive caregiver, and, most important, participation of the patient. If the disease is not terribly aggressive, therapy with nonsteroidal anti-inflammatory drugs is appropriate initially. If no response is obtained within 2 to 3 weeks, a new dose or different nonsteroidal agent is recommended. In many patients, aspirin, particularly if enteric-coated, is successful and very cost-effective. Disease-modifying antirheumatic drugs (DMARDs) are sometimes being used earlier in disease than previously. Hydroxychloroquine sulfate (Plaquenil Sulfate), auranofin (Ridaura), or sulfasalazine (Azulfidine, S.A.S.-500) is sometimes effective for early rheumatoid arthritis. For patients with more aggressive disease, intramuscular gold is the drug of first choice, and it is the only one that has been shown to decrease the rate of formation of new erosions. Significant toxic reactions occur in 30% to 40% of patients, however. D-penicillamine (Cuprimine, Depen) and azathioprine (Imuran) can be used if intramuscular gold is unsuccessful. Methotrexate (Rheumatrex Dose Pack) is the newest DMARD approved for treatment of rheumatoid arthritis. Its onset of action is rapid, and it is an effective anti-inflammatory agent. Its toxicity in patients with rheumatoid arthritis is not yet fully understood, however. Combination therapy with DMARDs is in its infancy, but such treatment is likely to become more prevalent in the future.

Adrenal Cortex Hormones↗
PubMed1990

Biliary elimination of low-dose methotrexate in humans.

We studied the pharmacokinetics of methotrexate (MTX) in a 64-year-old man with rheumatoid arthritis. After 6 months of treatment, acute clinical complications arose, requiring emergency laparotomy and cholecystotomy. A biliary tube was inserted, and this allowed for direct analysis of the bile. The pharmacokinetics of 2 separate doses of MTX (orally and intravenously) were assessed (dosage 10 mg/m2). No substantive differences in the pharmacokinetics were found between pre- and post-cholecystotomy MTX treatment, including clearance rates, volumes of distribution, and terminal half-lives. The results, however, demonstrated a change in the bioavailability of the drug (decreasing from 84.7% to 38.9%). Based on extrapolations of the data, with assumed rates of bile flow, the findings also suggest that there is substantial biliary elimination of MTX (8.7-26.0%) and its principal 7-hydroxy metabolite (1.5-4.6%).

Arthritis, Rheumatoid↗
PubMed1990

Skin score. A semiquantitative measure of cutaneous involvement that improves prediction of prognosis in systemic sclerosis.

Cutaneous sclerosis, assessed yearly by a semiquantitative skin scoring technique (sum of 10 body areas, each scored on a scale of 0-3 for tethering, by clinical palpation), and outcome at 10 years were evaluated in 90 systemic sclerosis patients enrolled in a 3-year, prospective drug trial. The inverse relationship of survival to the skin score at study entry (increasing skin score associated with decreasing survival) (P less than 0.003) was more significant than was the relationship found by using classification schemata that rely only on distribution of cutaneous sclerosis. Six-year survival was 40% in patients with entry skin scores greater than or equal to 15 and 73% when skin scores were less than 15 (P less than 0.005). An entry skin score greater than or equal to 15 was associated with a high risk of early fatal renal and cardiac complications.

Adult↗
PubMed1990

Aspirin, hydroxychloroquine, and hepatic enzyme abnormalities with methotrexate in rheumatoid arthritis.

Levels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in patients with rheumatoid arthritis from 5 centers involved in the Arthritis, Rheumatism, and Aging Medical Information System were correlated with the use of specific antirheumatic medications. Elevated levels of SGOT and SGPT were most frequent in patients taking salicylates and methotrexate (MTX) and least frequent in patients taking hydroxychloroquine. The combination of MTX and salicylates greatly increased the frequency of abnormal liver enzyme values. In contrast, the addition of hydroxychloroquine to a regimen of either MTX or aspirin essentially eliminated the SGOT and SGPT abnormalities. Results from all 5 centers were consistent and remained so after adjustment for age, sex, and disease duration. Knowledge of these important drug interactions may permit continuation of MTX therapy in patients in whom the drug might otherwise be discontinued.

Alanine Transaminase↗
PubMed1990

Effect of aspirin and sulindac on methotrexate clearance.

The pharmacokinetics of low dose methotrexate (MTX) were evaluated in 12 rheumatoid arthritis patients in the presence and absence of steady-state levels of salicylic acid (ASA) and sulindac (SU). Using a Latin square design, patients were given MTX plus ASA (mean 3.4 g/day), MTX plus SU (mean 400 mg/day), or MTX alone. On a background of at least one year of regular MTX therapy, patients received 10 mg/m2 MTX iv (mean 17.8 mg) given after at least 2 weeks of treatment with each of the above regimens. Plasma concentrations of MTX and 7-hydroxymethotrexate (7-OH-MTX) were measured using HPLC. No differences in MTX clearance (Cl) were found comparing MTX alone, MTX + ASA, and MTX + SU. However, if one particular subject that had a very low clearance when receiving MTX alone was excluded, there was a statistically significant decrease in MTX clearance when either ASA or SUL were present. It is also noteworthy that ASA significantly increased the exposure of the subject to 7-OH-MTX and, to a lesser extent, so did sulindac. Since 7-OH-MTX has been shown to be an active metabolite when given for cytotoxic effects at higher doses and because it has been show to be nephrotoxic at doses a thousand-fold greater than used in rheumatoid arthritis, nonsteroidal anti-inflammatory drugs should be used cautiously with MTX until further large scale safety studies are conducted. The data indicate that if a clinically significant interaction were to occur, ASA is more likely than SU to interact with MTX.

Arthritis, Rheumatoid↗
PubMed1990

Thyroid dysfunction in a prospectively followed series of patients with progressive systemic sclerosis.

Thirty-nine patients with progressive systemic sclerosis (PSS) in stable clinical conditions were extensively evaluated for the presence of thyroid disease. Two patients had previously undetected hypothyroidism while 7 additional patients had normal serum thyroid hormone levels but an exaggerated TSH response to thyrotropin-releasing hormone (TRH) administration, consistent with subclinical hypothyroidism. Four of the 9 subjects with abnormal TRH responses had positive antithyroid antibodies and of the remaining 5, 4 had been on chlorambucil or prednisone. Basal TSH and TSH response to TRH were significantly higher in PSS patients as a group when compared to a control group and increased with increasing duration of PSS. Serum antithyroid antibodies (antithyroglobulin and/or antimicrosomal antibodies) were positive in 18% and thyroid scans were abnormal in 18% of the patients. The euthyroid sick syndrome was not seen. Our findings indicate an increased frequency of, sometimes previously unsuspected, clinical and subclinical hypothyroidism in stable PSS patients which appears to be autoimmune in nature and becomes more prevalent with increased PSS duration. Careful and regular monitoring of the thyroid function in PSS patients is advisable.

Adult↗
PubMed1990

Proposition: methotrexate should not be the first second-line agent to be used in rheumatoid arthritis if NSAIDs fail.

Although methotrexate (MTX) is an effective antirheumatic drug, it cannot clearly be defined as a disease modifying antirheumatic drug (DMARD), when this term is characterized by its effect on radiographs or laboratory data. Current data, in the form of small studies or case reports, show that MTX's hepatic toxicity is not yet fully defined, that its acute pulmonary toxicity is significant, that systemic fungal infections may be associated with MTX use in rheumatoid arthritis (RA), that unexplained significant weight loss can be a problem, and that the consequence of drug interactions with MTX are not yet fully known. Thus, although clearly an effective antiinflammatory drug in RA, the place of MTX in the RA armamentarium is not fully defined. For this reason, MTX should not at present be used as the first second-line agent in RA after nonsteroidal antiinflammatory drugs (NSAIDs) fail.

Anti-Inflammatory Agents↗
PubMed1990

Rational use of disease-modifying antirheumatic drugs.

The currently available, most frequently used disease-modifying antirheumatic drugs (DMARDs) include auranofin, azathioprine, D-penicillamine, gold sodium thiomalate, hydroxychloroquine, methotrexate (amethopterin) and sulphasalazine. Controlled trials of these agents are reviewed to compare their relative efficacy and tolerability. Tender joint counts decreased with all drugs, as did joint swelling (measured as the percentage of patients with greater than or equal to 50% improvement in joint swelling). Tender joint count decreased by 8 to 57% in drug-treated patients, compared with 3 to 30% (1 study exceeded this degree of placebo response) in the placebo groups. The ratio of drug to placebo improvement usually averaged greater than 2. A 50% improvement in joint swelling occurred in between 15 and 65% of drug-treated patients. Time to onset of response varied from 6 weeks (with methotrexate) to as long as 18 months (some patients on hydroxychloroquine). The remission rate was inconsistent and unusual in controlled studies (5 to 7%), but very high in some open studies (e.g. 43%). While up to 8% of patients on DMARDs stopped therapy secondary to unsatisfactory therapeutic response (with 1 exception) up to 43% of placebo patients discontinued therapy for this reason. The ratio of dropouts for unsatisfactory therapeutic response for DMARD compared to placebo was less than 1 in 16 of 22 studies, and it was usually less than 0.5. Laboratory data examined include ESR, rheumatoid factor (RF), immunoglobulins and radiographic data. Ratios of decreases in ESR, comparing drug and placebo, were usually greater than 2. ESRs decreased from 3.6 to 27 mm/h, with gold sodium thiomalate, auranofin and methotrexate being most effective relative to placebo. RF decreased by greater than or equal to 2 tube dilutions in 15 to 53% of the DMARD groups but also decreased in up to 26% of placebo patients, with ratios of drug: placebo usually greater than 2. Immunoglobulins tended to decrease with DMARDs but the data are fragmentary. Radiographic evidence that a drug slows the rate of bony damage is strong evidence that it is a DMARD. These data, however, are not easily available because measurements of bony damage is insensitive and difficult. The best evidence of radiographic efficacy exists for gold, although the data are not uniform even here. Studies with other DMARDs suffer from lack of convincing control populations, methodological failures or small numbers, although trends exist showing that azathioprine and D-penicillamine (and perhaps sulphasalazine and methotrexate) may also slow bony deterioration. The other side of efficacy, of course, is tolerability.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Inflammatory Agents↗
PubMed1990

Adverse experience with methotrexate during 176 weeks of a longterm prospective trial in patients with rheumatoid arthritis.

Adverse experience occurred with a high frequency in a longterm (greater than 3 years), prospective, double blind, followed by an open trial of methotrexate (MTX) therapy in 45 patients with rheumatoid arthritis (RA). Adverse experiences occurred in 96% of patients, and the discontinuation rate was 44% over 176 weeks. No hepatic or pulmonary fibrosis occurred. Unusual toxicities included weight loss (2 patients), systemic fungal infections (2 patients), and transient noncirrhotic ascites (1 patient). Baseline white blood cell counts and creatinine may help predict adverse experiences. The full dose-toxicity spectrum of MTX RA is not yet fully defined.

Arthritis, Rheumatoid↗