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Biomedical subjects

N L Gottlieb

Publications and source records attributed to N L Gottlieb.

At least 19 recordsLinked to original sources
PubMed1986

Pharmacology of auranofin: overview and update.

Auranofin, the only approved oral gold complex of value in suppressing rheumatoid arthritis, differs from injectable gold compounds molecularly and pharmacologically. Although comparably efficacious, the side-effect profiles of oral and intramuscular gold differ, and the withdrawal rate for adverse reactions is several-fold lower with auranofin. Considerably less elemental gold is available to the internal milieu with auranofin than with gold sodium thiomalate (3 mg/week vs. 25 mg/week), a difference reflected in lower blood, synovial fluid and tissue gold levels. Approximately 25% of the administered auranofin dose is absorbed orally, and 85% is recovered in feces. Serum gold levels are 300-400 micrograms/dl one week after injectable gold and 60-70 micrograms/dl daily with auranofin (6 mg/d). But, surprisingly, the fraction of gold associated with the red blood cell fraction is higher with auranofin. Blood gold levels do not correlate with clinical response to treatment or frequency or type of adverse reaction, regardless of the gold preparation used. Similar results obtain with penicillamine. Methotrexate blood levels are not related to the development of hepatic fibrosis. The mechanisms of gold action in rheumatoid arthritis are unknown, despite the laboratory definition of multiple antiinflammatory, immunologic and other effects. Sulfhydryl binding activity, an established property of injectable gold compounds and penicillamine of potential importance pharmacodynamically, is limited with auranofin.

Administration, Oral↗
PubMed1979

Primary familial bilateral carpal tunnel syndrome.

We identified bilateral carpal tunnel syndrome in 19 of 43 living persons of a nonconsanguineous family. No single common etiologic feature was seen. Sixty-three percent of the afflicted kindred had symptomatic digital flexor tenosynovitis. Noninflammatory thickening of the flexor retinaculum or tendon sheaths, or both, was the commonest surgical finding. The 44% prevalence, early age of onset, and equal sex ratio differ from idiopathic carpal tunnel syndrome. Family pedigree suggests an inheritable disorder transmitted by an autosomal dominant gene with a high degree of penetrance.

Adult↗
PubMed1979

Metabolism and distribution of gold compounds.

The pharmacokinetics of gold in blood and urine are compared during intramuscular and oral chrysotherapy for rheumatoid arthritis. Blood gold levels are 3 to 10 fold higher with injectable aurothioglucose and gold sodium thiomalate (50 mg/week) than with oral auranofin (6 mg/day). But, the serum half-life of the parenteral compounds is significantly shorter (5.5 days) than the oral agent (14-21 days). The gold content of urine is nearly 10 times higher with the intramuscular compounds than with the oral drug. The excretory pathways and tissue distribution of gold during conventional intramuscular chrysotherapy are reviewed. Forty percent of a 50 mg injection of gold sodium thiomalate is excreted in 7 days, of which 70% is recovered in the urine. Highest gold concentrations are found in the reticuloendothelial system, adrenal glands and kidneys, while the bone marrow, liver, skin and bone contain the greatest quantities of gold.

Animals↗
PubMed1979

Gold compounds in rheumatoid arthritis: clinical-pharmacokinetic correlates.

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.

Aging↗
PubMed1979

Gold excretion and retention during auranofin treatment: a preliminary report.

Auranofin, an oral gold compound, was administered to 12 patients with rheumatoid arthritis using 2 dosage schedules (3 mg or 1 mg twice daily for 8 weeks, and then once daily for 18 weeks). In addition to outpatient clinic monitoring, all patients were admitted to a metabolic ward for 3 days for collection of 24 hr daily urine and feces. Gold content of excreta was determined by atomic absorption spectroscopy. Seventy-three per cent of the administered gold was recovered in the urine and feces of patients receiving 3 mg b.i.d., and all the gold was recovered in those taking 1 mg b.i.d. Ninety-five per cent of the recovered gold was in the feces and 5% was in the urine. These findings contrast with those observed during intramuscular (gold sodium thiomalate) chrysotherapy: 40% of the injected dose was recovered, 70% in urine, 30% in feces. Less tissue gold retention occurred with oral gold than with parenteral therapy. Following 20 weeks of auranofin (6 mg/day) chrysotherapy approximately 66 mg of gold was retained. By comparison, 300 mg of gold was retained after injectable gold sodium thiomalate treatment. The significance of these findings is discussed.

Adult↗
PubMed1977

Allopurinol-associated hand and foot deformities in chronic tophaceous gout.

Telescoped digits of the hands and feet developed in a 69-year-old male with severe chronic tophaceous gout during allopurinol treatment. Extensive osseous tophi, resorbed rapidly during therapy with this xanthine oxidase inhibitor and not replaced by new bone matrix, were responsible for the deformity. Several hypotheses are advanced to explain the failure of bone erosions to heal.

Aged↗
PubMed1977

Hand flexor tenosynovitis in rheumatoid arthritis. Prevalence, distribution, and associated rheumatic features.

Tenosynovitis of one or more flexor tendons of the hand (mean 3.1 tendons per patient) was noted in 55% of 100 patients with rheumatoid arthritis (RA) examined periodically during a mean period of 5 years. The third flexor tendon was involved most frequently (71% of patients), followed by the second (62%), fourth (53%), fifth (27%), and first (13%). Patients with flexor tendonitis (FT) had a significantly higher prevalence of rheumatoid nodules (56% vs 33%), carpal tunnel syndrome (47% vs 13%), wrist extensor tenosynovitis (47% vs 9%), and elbow epicondylitis (22% vs 7%) than patients without FT. Dupuytren's contracture, DeQuervain's tenovaginitis, flexor carpi radialis and ulnaris tendonitis, and Achilles tendonitis were found exclusively in patients with FT. A control group of 50 non-RA patients with FT had statistically fewer diseased tendons per patient (mean 1.5) and a different digital distribution, the thumb being affected more frequently (P less than 0.05) than in RA patients.

Achilles Tendon↗
PubMed1977

Acute myocardial infarction following gold sodium thiomalate induced vasomotor (nitritoid) reaction.

A vasomotor (nitritoid) reaction occurred following an initial injection of gold sodium thiomalate (GST; Myochrysine) in a 69-year-old man with rheumatoid arthritis (RA). An acute anterior wall myocardial infarction, documented by serial electrocardiographic and serum enzyme changes, developed immediately thereafter. A second patient, a 49-year-old man with RA and a history of GST-associated vasomotor reactions, was monitored clinically and electrocardiographically after GST administration. Sinus tachycardia developed and peripheral blood pressure fell within 2 minutes of injection, simultaneous with the onset of vasomotor symptoms. Vasomotor reactions from GST may compromise myocardial perfusion by their action on arteriolar smooth muscle, and thus result in peripheral vasodilatation, or they may act by adrenergic discharge initiated by such a reaction, and thus increase myocardial work and oxygen demand. Aurothioglucose (Solganal), rarely produces vasomotor reactions, and may be preferred to GST in elderly RA patients with concomitant cardiovascular disease or atherosclerosis.

Aged↗
PubMed1977

Gold compounds in rheumatoid arthritis. Report of a symposium.

A vast accumulation of clinical experience and controlled studies justifies the use of gold compounds in selected cases of rheumatoid arthritis. The striking therapeutical efficacy observed in some patients has stimulated active research to clarify the pharmacokinetics and mechanisms of action of gold compounds. Based on this knowledge, the possibility of selecting gold-responsive patients may be enhanced, and the frequency of adverse reactions decreased. Liberal indications and inexperience in administration and control have given gold therapy mixed reputation. A symposium in Umeå, Sweden, summarized present knowledge and current concepts among Scandinavian rheumatologists on the rational use of gold compounds.

Arthritis, Rheumatoid↗