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Biomedical subjects

D E Furst

Publications and source records attributed to D E Furst.

At least 181 records · Page 10Linked to original sources
PubMed1984

Clinical and serological comparison of 17 chronic progressive systemic sclerosis (PSS) and 17 CREST syndrome patients matched for sex, age, and disease duration.

This study compares the clinical and serological differences between 17 PSS and 17 carefully matched CREST patients. Patients were matched for sex, age by decade, and, importantly, disease duration (11.2 +/- 9.2 vs. 12.0 +/- 9.3 years). Muscular and skin involvement were greater for the PSS groups (p less than 0.02) and pulmonary involvement was also greater (p less than 0.05), at least for non-smoking PSS patients. On the other hand no clinically significant differences were found between groups for other visceral involvement--including comparisons of gastrointestinal, cardiovascular, and renal involvement. There were also no laboratory differences except in anti-RNP antibody (p less than 0.04).

Adult↗
PubMed1984

Case control study of antibodies to ENA in progressive systemic sclerosis patients.

Sixteen antibody to extractable nuclear antigen (anti-ENA) (+) and 16 anti-ENA(-) progressive systemic sclerosis (scleroderma, PS) patients were matched for disease duration, age, and sex in a case control study of antibody to ENA (anti-ENA) in scleroderma. Anti-ENA (+) PSS patients more frequently fulfill only minor criteria for PSS than anti-ENA (-) PSS controls (31% vs 0%). Anti-ENA(+) patients had less skin and muscle involvement (p less than 0.05) than their matched controls and tended to overlap more with other diseases (3 vs 0 patients). Besides antinuclear antibody and ENA, no significant serological differences were found between the 2 groups.

Antibodies, Antinuclear↗
PubMed1983

Low-dose D-penicillamine therapy in rheumatoid arthritis. A controlled, double-blind clinical trial.

Two hundred twenty-five patients with active severe rheumatoid arthritis were admitted to a multiclinic, controlled, double-blind trial comparing the use of 500 mg D-penicillamine per day, 125 mg D-penicillamine per day, and placebo. One hundred seventy-one patients completed at least 30 weeks of therapy. The 500 mg D-penicillamine group demonstrated statistically significant improvement over the placebo group in grip strength, average circumference of swollen proximal interphalangeal joints, and patient assessment. While the trend was for greater improvement with the larger dose of D-penicillamine, there was no statistically significant difference among the 3 groups in duration of morning stiffness, walking time, physician's assessment, number of swollen joints, or scores for tender and swollen joints. The slight increase in efficacy of higher dose D-penicillamine was associated with increased toxicity.

Adolescent↗
PubMed1983

Clinical pharmacology of tolmetin: comparisons in rheumatoid arthritis patients and normal volunteers.

The pharmacokinetics of tolmetin sodium were studied in five patients with rheumatoid arthritis (RA) and five normal volunteers to determine whether data derived from normals could be applied to RA patients. In addition, prostaglandin E (PGE) levels in synovial fluid were compared with tolmetin levels in serum and synovial fluid. Both groups received 400 mg tolmetin every 6 hours for seven days. During a 24-hour washout period after the dose of tolmetin (400 mg) on day 8, blood and urine samples were obtained from all study participants, and synovial fluid samples from the RA patients only. The patients continued into a second 24-hour drug-free period, after which they received a single 400-mg dose of tolmetin. Blood and urine samples were again collected. No clinically or statistically significant differences in tolmetin kinetics between normal volunteers and RA patients were found. A comparison of multiple-dose and single-dose results in the patient group showed an 11 per cent increase in the tolmetin serum concentration after multiple dosing. Total PGE levels in synovial fluid remained significantly depressed in the patient group for 24 hours after the 400-mg test dose of tolmetin on day 8. These findings suggest that tolmetin serum kinetics may not be an appropriate indicator of the duration of biologic activity of tolmetin.

Adult↗
PubMed1983

Volume shifts and protein binding estimates using equilibrium dialysis: application to prednisolone binding in humans.

Sizable volume shifts can occur during equilibrium dialysis. This net movement of water, presumably caused by the osmotic effect of plasma proteins, reduces the concentration of binding proteins. In this paper the theory of protein binding estimation is extended, equations are developed for calculating the unbound and bound drug concentrations at dialysis equilibrium by correcting for the dilution of the proteins, and the equations are applied to a study of prednisolone. To demonstrate the importance of correcting for the volume shift, the parameters of a model in which prednisolone binds to corticosteroid-binding globulin, a protein with a limited capacity, and albumin were estimated. Unbound and bound concentrations were determined by correcting for both volume shifts (average 31%) and loss of drug to the buffer side, by correcting only for loss of drug to buffer side, and by making no correction at all (the usual method of treating equilibrium dialysis data). The error introduced by neglecting volume shifts was analyzed by comparing the parameter values obtained using the three methods. The results confirm the need to adjust for volume shifts and imply that reported binding constants obtained by equilibrium dialysis may be in error for many substances.

Blood Proteins↗
PubMed1983

Availability of salicylate from salsalate and aspirin.

Salicylate availability from salsalate (SSA) and aspirin (ASA) was examined in six rheumatoid arthritis patients in a multiple-dose double-blind crossover study. Doses contained equimolar amounts of salicylic acid. After initial ASA treatment to achieve therapeutic salicylate levels (150 to 300 micrograms/ml) the patients received equimolar doses of SSA or ASA. When steady state was achieved patients were hospitalized, and blood and urine specimens were obtained during three dosing intervals and during the washout period that followed. Thereafter, patients were placed on the alternate medication for at least a week and the in-hospital pattern was repeated. Despite insignificant differences in absorption of the formulations, as measured by urinary salicylate recovery, the plasma salicylic acid AUC was lower after SSA. Evidence indicates that this apparent lower availability of salicylate from SSA is due to incomplete hydrolysis to salicylic acid, the unhydrolyzed SSA being excreted mainly as glucuronide conjugates.

Arthritis, Rheumatoid↗
PubMed1982

Relationship of serum naproxen concentration to efficacy in rheumatoid arthritis.

Twenty-four patients with rheumatoid arthritis were tested in a randomized, double-blind. Latin-square comparison of 250, 750 and 1500 mg of naproxen daily. Each received each dose for 2 wk and baseline disease activity was established during withdrawal of medication before and after the study. Nine standard measures of efficacy were tested at each evaluation. No order effect or change in baseline was found. Total and unbound naproxen concentrations were measured by high-pressure liquid chromatography and equilibrium dialysis, respectively. A linear dose-response relationship (P less than 0.05) was demonstrated between naproxen and joint count, patient's pain assessment, activities of daily living index, physician's global assessment, and grip strength. The relationship to patients' global assessment was of uncertain significance (P less than 0.07). A positive dose to serum level correlation (1, 2, and 12 hr after dose) was apparent (r greater than 0.78). When patients were defined as responders or nonresponders by a summed efficacy score, there was a serum concentration-response relationship; the percentage of responding patients increased with each serum level quartile: 25%, 31%, 59%, and 75%. Patients with a trough total serum naproxen concentration under 18 micrograms/ml did not respond, while 76% of patients with trough total serum concentrations above 50 micrograms/ml responded. No serum naproxen toxicity level relationship was established.

Adult↗
PubMed1982

Tolmetin kinetics and synovial fluid prostaglandin E levels in rheumatoid arthritis.

Tolmetin kinetics were determined in the plasma and synovial fluid of five rheumatoid arthritis patients after they had ingested tolmetin (400 mg every 6 hr) for 7 days. Tolmetin was rapidly absorbed, with average peak levels in plasma and synovial fluid occurring at 45 min and 2 hr. The drug concentration in synovial fluid was higher than that in plasma for prolonged periods, while the rates of elimination from both plasma and synovial fluid were similar. The average half-lives of tolmetin in plasma and synovial fluid were 6.77 +/- 1.47 hr and 6.90 +/- 2.3 hr. Total prostaglandin E levels in synovial fluid of these patients were suppressed for at least 24 hr after the last dose of tolmetin, suggesting that PGE synthesis continues to be suppressed even by the very low concentrations of tolmetin remaining after 24 hr.

Adult↗
PubMed1981

Abnormalities of pulmonary vascular dynamics and inflammation in early progressive systemic sclerosis.

Abnormalities of pulmonary function were studied in 10 patients with progressive systemic sclerosis (PSS) and 3 control subjects. All underwent 81M krypton lung scanning and total body gallium scanning. Immune complexes were measured by Raji cell radioimmunoassay and polyethylene glycol (PEG) assay. Perfusion scans were abnormal in 7 of 9 patients, and 5 of 9 showed a decrease in pulmonary perfusion after cold challenge. Increased gallium uptake was noted in the lungs of 6 of 9 patients. Krypton scans were normal in the control group. Elevated immune complexes were noted in 8 of 10 patients by the Raji assay and in 5 of 10 with the PEG assay. Efforts to separate patients with PSS into subgroups may lead to a better understanding of and advances in therapy for PSS.

Adult↗
PubMed1981

The relationship arrhythmias and conduction disturbances to other manifestations of cardiopulmonary disease in progressive systemic sclerosis (PSS).

Disorders of rhythm and conduction are characteristic of the cardiac involvement in progressive systemic sclerosis (PSS), but their over-all frequency in PSS is not well established. Therefore, 46 ambulatory patients with PSS underwent several tests of cardiopulmonary function, including a 24-hour continuous electrocardiogram (Holter monitor). Conduction disturbances (sinus node dysfunction, first-degree heart block, pre-excitation), supraventricular arrhythmias (supraventricular tachycardia, atrial fibrillation, premature contractions of atrial or junctional origin) and ventricular arrhythmias (ventricular tachycardia, multifocal premature contractions) were observed on Holter monitoring in 26 subjects. Although these arrhythmias and conduction disorders were predictably observed in patients who complained of palpitations or syncope, or who had an electrocardiogram which showed first-degree heart block, ventricular bigeminy, left anterior superior hemiblock, prolonged p wave, right or left axis deviation, right or left ventricular hypertrophy, pathologic Q waves or low voltage, they were often found in patients who lacked other clinical evidences of heart disease. Arrhythmias and conduction disturbances were not significantly more frequent among patients with cardiomegaly or interstitial change on chest roentgenogram nor were they related to the presence or severity of abnormal lung function. This study suggests that Holter monitoring may be a valuable adjunct in evaluating heart disease in PSS.

Adult↗
PubMed1981

Skeletal findings in progressive systemic sclerosis (scleroderma).

Radiographs were reviewed of the chest, hands, and feet of 55 patients with progressive systemic sclerosis. These patients had been selected so as to exclude overlap syndromes, particularly mixed connective tissue disease. Soft tissue changes included flexion deformities, generalized or localized atrophy, and dystrophic calcifications. While resorption of distal phalanges was the most common bony change, osteolysis in other sites (feet, ribs, and mandibles) was also frequent. Twelve of 55 patients showed radiographic evidence of inflammatory arthritis, ranging from isolated to generalized joint destruction, that could not be attributed to overlap with rheumatoid arthritis or mixed connective tissue disease.

Adult↗
PubMed1981

Pulse methylprednisolone in rheumatoid arthritis: a double-blind cross-over trial.

Ten patients with rheumatoid arthritis unresponsive to conventional therapy participated in a double-blind cross-over trial in which they randomly received either a "pulse" or 1 g of methylprednisolone or placebo, intravenously, once a month for 6 months. Both the drug-first and placebo-first groups had the same mean American Rheumatism Association functional classification, 2.5. During the study patients on methylprednisolone "pulses," compared to placebo, showed significantly better mean tender-joint counts, walking times, and grip strength (p < 0.05). The drug-treated patients also had significantly lower levels of immune complexes (p < 0.01) and IgG (p < 0.01). Effects could still be measured an average of 2.9 +/- 0.4 months after the last dose of methylprednisolone. No significant side effects were noted during the therapy. Despite these findings, "pulse" methylprednisolone did not appear to significantly retard radiologic progression of the arthritis.

Antigen-Antibody Complex↗
PubMed1981

The prevalence of conduction defects and cardiac arrhythmias in progressive systemic sclerosis.

A prospective noninvasive electrocardiographic study was done on 50 patients with progressive systemic sclerosis. Thirty-two percent had abnormalities on the resting electrocardiogram, of which the commonest were left anterior fascicular block (16%) and first-degree heart block (8%). The 24-hour ambulatory continuous tape-recorded electrocardiograms showed serious abnormalities in 62% of the patients: supraventricular tachycardias (32%), conduction disturbances (14%), coupled ventricular extrasystoles (20%), and ventricular tachycardia (10%). Intracardiac electrophysiologic data were obtained in 20 of these patients, and functional abnormalities of the sinus node, atria, and atrioventricular node were noted in seven, nine, and 10 patients, respectively. One patient had prolonged His-Purkinje conduction time. Of the 20 patients who had electrophysiologic studies, only six had entirely normal findings. These results suggest a much higher degree of cardiac involvement in progressive systemic sclerosis than previously believed. We postulate that the first-degree heart block and supraventricular tachycardias may derive from a similar pathologic process, namely, fibrous atrophy of the proximal atrioventricular node.

Adult↗
PubMed1979

A syndrome resembling progressive systemic sclerosis after bone marrow transplantation. A model for scleroderma?

Six long term survivors of bone marrow transplants developed a syndrome similar to progressive systemic sclerosis (PSS). Cutaneous involvement (6/6), pulmonary disease (6/6), musculoskeletal involvement (4/6), keratoconjunctivitis/positive Schirmer's test (4/6), Raynaud's phenomenon (2/6), and renal and cardiac disease (1/6) were similar to findings in PSS patients. T and B lymphocyte counts and functions were also similar. This PSS-like syndrome, including visceral involvement, after bone marrow transplantation lends support to an immunologic hypothesis of the pathogenesis of progressive systemic sclerosis.

Antigen-Antibody Complex↗
PubMed1979

Salicylate clearance, the resultant of protein binding and metabolism.

Steady-state plasma salicylate concentrations and protein binding were examined in 9 normal subjects to determine relationships among daily dose, total and unbound salicylate concentrations, and total and unbound clearances. Aspirin doses ranging from 0.66 to 4.0 mg/kg/hr were given to steady state. Free and total salicylate concentrations were measured with spectrophotometric, fluorimetric, and equilibrium dialysis techniques. Although unbound clearance decreased over the therapeutic range, total clearance was unchanged. The former is a consequence of saturable metabolism; the latter, of saturable plasma protein binding as well as saturable metabolism. The fraction unbound increased linearly with unbound concentration. Clearance determined at 1.8 mg/kg/hr was used to predict levels obtained at higher aspirin doses. Analysis of residuals was used to ascertain the accuracy of the prediction. The coefficient of variation from prediction among subjects was found to be +/- 14%. It is concluded that, in normal subjects, salicylate clearance changes relatively little over the therapeutic range because the increasing fraction unbound compensates for decreasing clearance of unbound drug.

Adult↗