Search PubMed⌕ Search

Biomedical subjects

D E Furst

Publications and source records attributed to D E Furst.

At least 145 records · Page 8Linked to original sources
PubMed1990

Elevated serum levels of soluble interleukin 2 receptor, interleukin 2 and neopterin in diffuse and limited scleroderma: effects of chlorambucil.

In a study of 48 patients with systemic sclerosis (SSc). elevated serum levels of soluble interleukin 2 receptor (IL-2R), interleukin 2 (IL-2) and neopterin (indicators of lymphocyte/monocyte activation) were noted in 100, 44 and 40% of early untreated patients with SSc (11 diffuse, 5 Limited). Levels of IL-2R, but not IL-2 or neopterin, were lower in patients with longer duration of disease and possibly with chlorambucil therapy. Pharmacologic alterations of markers of humoral or cell mediated immunity may not be an accurate reflection of clinical efficacy of chlorambucil.

Adult↗
PubMed1990

Treatment of generalized systemic sclerosis.

Over the years, many encouraging uncontrolled studies extolling treatments of SSc have appeared, but initial impressions were not corroborated when controlled trials were done. This article points out that certain recent studies have effectively ruled out the use of some specific therapies for the general treatment of systemic sclerosis. Thus, sufficient data has been generated to rule out the use of n-acetylcysteine, colchicine, chlorambucil, cyclofenil, and DMSO, at least in disease of longer duration. Ketanserin and prostaglandin infusions probably also belong in this group, as they affect only Raynaud's phenomenon. Angiotensin enzyme inhibitors, while probably life-saving in renal crises, do not seem to affect the underlying systemic sclerosis per se. Another group of drugs has only limited supportive data and await well-controlled trials to prove or disprove their effectiveness. These include: 5-fluorouracil, D-penicillamine, drugs affecting platelet function (dipyridamole), and para-aminobenzoic acid. There are a few treatments which have potential. Factor XIII has only limited data using controlled trials, but what does exist seems positive. Apheresis is encouraging, although the success of this treatment modality may be dependent upon a "combination" approach. Ongoing studies with gamma-interferon, photopheresis, and the mast cell stabilizer ketotifen appear exciting, and we await reports of their use in scleroderma. On another level, new insights into genomic alterations in skin fibroblasts and T-cell proto-oncogene expression have contributed to the understanding of the pathogenesis of this disease at the cellular level and new methods to measure change in disease will help gauge response to therapy. Thus, we look forward to more definitive treatment of SSc in the future.

Humans↗
PubMed1989

Home central venous hyperalimentation in fifteen patients with severe scleroderma bowel disease.

Fifteen patients with severe scleroderma bowel disease began receiving home central venous hyperalimentation (HCVH) between 1979 and 1987. The major reasons for instituting HCVH were intestinal pseudo-obstruction, malabsorption, and malnutrition. Eleven patients had an improved quality of life. Serious complications encountered over these 15,700 catheter-use days were 2 episodes of septicemia and 2 episodes of superior vena cava obstruction. Seven patients died, but none directly from their gastrointestinal disease or from the HCVH.

Adult↗
PubMed1989

Immunosuppression with chlorambucil, versus placebo, for scleroderma. Results of a three-year, parallel, randomized, double-blind study.

Placebo and chlorambucil (0.05-0.1 mg/kg/day) were compared as treatments for scleroderma in a 3-year, randomized, double-blind, parallel study of 65 patients. Slopes of change over time, calculated for each organ system of each patient, failed to show significant differences between treatment groups. An immunosuppressive effect in the chlorambucil-treated group was shown by decreases in the white blood cell counts (P = 0.02), platelet counts (P = 0.04), lymphocyte counts (P = 0.001), IgA/IgM concentrations (P less than or equal to 0.05), and wheal size on mumps skin tests (P = 0.02). Three years of immunosuppressive treatment with chlorambucil did not benefit this scleroderma population.

Chlorambucil↗
PubMed1989

Pharmacokinetics of low-dose methotrexate in rheumatoid arthritis patients.

The pharmacokinetics and bioavailability of low-dose methotrexate (MTX) (10 mg/m2) were evaluated in 41 subjects who had definite or classical rheumatoid arthritis as defined by the American Rheumatism Association criteria. Subjects received 10 mg/m2 (to the nearest 2.5 mg) of MTX in a single oral dose and a single intravenous (iv) dose one week apart. Serum concentrations for this low-dose regimen were monitored using a radiochemical ligand binding assay. The results indicate the MTX is cleared from the plasma at a rate of 84.6 mL/min/m2. The terminal half-life was approximately 6 h. The volumes of distribution at steady state and for the central compartment were 22.2 and 13.5 L/m2, respectively. The mean residence time in the body, in the systemic circulation, and in the periphery were estimated to be 4.7, 3.0, and 1.7 h, respectively, with a peripheral single-pass mean transit time of 6.0 h and an intrinsic mean residence time in the periphery of 7.9 h. The mean absorption time was 1.2 h and the oral bioavailability was 0.70. The ratio of synovial fluid concentration to serum concentration 4 and 24 h after a dose was found to be approximately 1.0, indicating that at least within that time range serum and synovial fluid concentrations are approximately equal. Because of conflicting results and insufficient data from previous high-dose pharmacokinetic studies, it is difficult to say whether or not low-dose MTX pharmacokinetics differs from those of high-dose MTX.

Administration, Oral↗
PubMed1989

Environmentally-induced systemic sclerosis-like illness.

Interaction of the host immune system with certain substances found in the environment will, in the presence of other unknown factors such as genetic susceptibility, lead to aberrant immune responses manifested as disease. In most of the conditions discussed above, simple removal from exposure to the offending agent does not lead to resolution. This suggests that an ongoing response has been triggered which cannot immediately be turned off, perhaps due to continued presence of the substance such as in human adjuvant disease where paraffin or silicone has been found in lymphoid tissue. Scleroderma remains a disease of uncertain cause for which our present treatment is inadequate. Illnesses presented in this chapter resemble the natural form of the disease in many ways and may provide useful insight into its pathogenesis. In the short term, recognition of exposure to environmental hazards which appear to pose risk will prevent additional cases of disabling illness. Study of chemically induced forms of scleroderma may, in the future, allow us to predict potential toxicity of chemically similar compounds. If we could learn how they trigger disease, researchers might be able to apply the information to understanding the pathogenesis of naturally-occurring scleroderma.

Environmental Exposure↗
PubMed1989

Increasing methotrexate effect with increasing dose in the treatment of resistant rheumatoid arthritis.

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.

Activities of Daily Living↗
PubMed1988

The basis for variability of response to anti-rheumatic drugs.

The reasons for variability of response to anti-rheumatic drugs are myriad. All the factors that contribute to kinetic variability, for example, contribute to differences in response between individuals. Thus, differences in drug formulation, protein binding, drug metabolism and excretion, all contribute to variable responses. Further, factors which contribute to differential clinical response/toxicity must be considered. Here, age, gender, genetic background, weight, concomitant diseases and numerous environmental factors come into play. Among the environmental factors are such diverse elements as smoking, activity and diet. Finally our ability to measure change, be it in response or toxicity, is limited, introducing apparent variability (as much as real variability) into the equation. While we cannot, at present, delineate the contribution of each factor to individual variability, it is hoped that systematic, persistent effort will help us understand and then control these elements, leading to improved ability to individualize therapy and decrease the variability of response to anti-rheumatic drugs.

Anti-Inflammatory Agents↗
PubMed1988

Serum concentration and dose-response relationships for carprofen in rheumatoid arthritis.

Thirty-eight patients with active, definite, or classical rheumatoid arthritis were tested in a double-blind, 3-week-per-arm, multiple-crossover, randomized, block-design comparison of 100, 300, 600, and 800 mg/day carprofen given b.i.d. A linear dose-response relationship was demonstrated for six of nine efficacy measures (p less than 0.052). A plasma concentration to therapeutic response relationship was shown just before or 1 to 2 hours after a dose (p less than 0.05) for seven efficacy parameters for the patients with at least three serum carprofen concentrations. By nonparametric analysis, with the patients divided into three equal groups, the percent of responders rose from 38.1% to 50% to 59.1%. Sixty-nine percent of patients responded when carprofen concentrations were greater than 10 micrograms/ml, whereas only 9% responded when they were below 1.9 micrograms/ml. Although only seven patients had limiting side effects, there was a tendency toward a dose-toxicity relationship through 600 mg daily carprofen.

Adult↗
PubMed1988

Seronegative and seropositive rheumatoid arthritis: radiographic differences.

Patients with seronegative and patients with seropositive rheumatoid arthritis (RA) have clinical, genetic, and immunologic differences. This study was undertaken to determine whether the two populations differ radiologically. Seventeen patients with seronegative RA were closely matched with seropositive control subjects. Radiographs of the hands and wrists were studied blindly, and disease severity was quantified with use of a modification of the Beaver Creek grading sheet. The following distinguishing features were also evaluated: osteosclerosis, new bone formation, carpal predominance, ankylosis (fusion), symmetry, and classical erosions. Seropositive patients had more severe disease, with larger and more numerous erosions, while the seronegative group had more osteosclerosis, carpal predominance, fusion, and new bone formation. Symmetry was equal in both groups. Although there were definite quantitative and qualitative differences between the two populations, radiologists should be cautious in using these criteria because of the great deal of overlap between the two groups.

Arthritis, Rheumatoid↗
PubMed1988

Clinically important interactions of nonsteroidal antiinflammatory drugs with other medications.

While many interactions between nonsteroidal antiinflammatory drugs (NSAID) and other drugs are reported, only a limited number of them are clinically important. These interactions can be divided into those explainable on mainly pharmacokinetic grounds, those explainable on interactions between pharmacokinetics and pharmacodynamics, and those that remain unexplained. Among those explainable on primarily kinetic grounds are interactions of NSAID with antacids, anticoagulants, hypoglycemics, methotrexate, lithium, probenecid, and phenytoin. More complex interactions between dynamics and kinetics are those relating NSAID interactions with diuretics, beta-blockers, other NSAID, and some anticoagulants. Finally important interactions whose causes are not understood include those between aspirin and corticosteroid, indomethacin and triamterene, and flurbiprofen with certain anticoagulants.

Adrenal Cortex Hormones↗
PubMed1988

Comparison of three pulse methylprednisolone regimens in the treatment of rheumatoid arthritis.

Twenty-nine patients with active rheumatoid arthritis entered a 6-week, parallel, randomized, double blind trial, comparing 1000 mg IV-methylprednisolone (MP), 320 mg IV-MP and 320 mg IM-MP. Although clinical benefit was noted in all groups, there were no differences among groups for duration of benefit (days: 1000 mg IV: 23.4; 320 mg IM: 17.2; 320 mg IV: 21.9) (p = 0.72), patient global scale (p = 0.57), or MD global scale (p = 0.36). Power to tell a 33% difference among groups for joint tenderness and patient global scale was 0.64 and 0.78. No serious drug related toxicity occurred. This preliminary study in a small patient group suggests that no large differences (33%) can be discerned among these 3 regimens. However, a larger study is indicated to reduce possible beta errors.

Arthritis, Rheumatoid↗
PubMed1987

A controlled study of concurrent therapy with a nonacetylated salicylate and naproxen in rheumatoid arthritis.

Previous studies of combinations of nonsteroidal drugs used in the treatment of rheumatoid arthritis (RA) have yielded conflicting results. We used standard methods to measure disease activity and high pressure liquid chromatography to measure plasma drug concentrations. We used doses of choline magnesium trisalicylate, adjusted to achieve therapeutic serum salicylate concentrations, and naproxen in a randomized, double-blind, placebo-controlled cross-over study of full dose trisalicylate (CMT), full dose naproxen (N), full dose of both (CMT-N), and half dose of both (cmt-n) to examine their relative efficacy and toxicity in treating RA. CMT-N was statistically superior to all other treatments in only 1 of 12 efficacy variables, but was equal to N and better than CMT or cmt-n for 7 variables. There were minimal differences among treatments for the other 4 efficacy variables. The mean percentage difference for the efficacy variables between CMT-N and N was 3%, between CMT-N and CMT was 10.6%, and between CMT-N and cmt-n was 10.5%. Thirteen percent of patients manifested toxic reactions during the initial open dose-adjustment salicylate run-in phase. During the double-blind phases of the study, CMT-N was more toxic than N, CMT, or cmt-n (7.5% versus 3.4%, 1.8%, and 3.7%, respectively). Tinnitus was more common when full-dose CMT was used; N (N or CMT-N) was associated with increased skin toxicity. Gastrointestinal complaints were equally common with all regimens. CMT-N, although sometimes statistically superior to CMT, N, or cmt-n, showed no clinically important additive or synergistic effect versus N or CMT alone.

Adult↗