The distribution of gold in Kupffer cells and in subcellular fractions of rat liver was studied at intervals following intraperitoneal injection of 195Au sodium thiomalate (Myochrysine). Kupffer cells, isolated by digestion of whole liver with Pronase, had radioactive gold counts per milligram of protein that were twice the counts in the digested liver supernatant. After fractionation of liver cells by differential centrifugation, radiogold was found predominantly in the nuclear, mitochondrial, and lysosomal fractions. When the distribution of isotope was related to the protein content, the highest gold concentration was found in the lysosomal fraction, where it was 28 times that in the soluble fraction. Most radiogold was nondialyzable, probably a result of binding to larger intracellular compounds. Approximately 95% of the nondialyzable gold was in the organelle membrane of attached to membrane-adsorbed material, as determined by treatment of dialyzed mitochondrial and lysosomal fractions with Triton X-100. These data suggest that the intracellular locus of gold action may reside in organelle membranes.

Animals↗

PubMedDate not supplied

Intratendon sheath corticosteroid treatment of rheumatoid arthritis-associated and idiopathic hand flexor tenosynovitis.

Flexor tenosynovitis (FT) is a common manifestation of rheumatoid arthritis (RA), contributing to hand deformity and manual dysfunction. The efficacy of intratendon sheath corticosteroids was assessed by reviewing the results of such treatment in 173 episodes of FT documented in 46 patients with definite or classic RA. Ninety-three percent of initial episodes resolved completely for 3 or more months (median: 25 months); tenosynovitis did not recur in 59%. The likelihood of a favorable response did not diminish with treatment of recurrent FT in a given digit. Comparable results were found in 52 FT episodes observed in 38 non-RA patients. No tendon sheath or soft tissue infection or tendon rupture ensued in either treatment group. The response was influenced by the specific corticosteroid preparation selected. Based on this experience, a trial of intratendon sheath corticosteroid injections prior to surgical intervention is recommended for RA patients with FT.

Arthritis, Rheumatoid↗

PubMedDate not supplied

Ocular chrysiasis correlated with gold concentrations in the crystalline lens during chrysotherapy.

The eyes of 11 patients with rheumatoid arthritis (RA) who received extended chrysotherapy (mean cumulative dose greater than 7 grams during a mean 6-year period) were examined biomicroscopically. Minute reddish-purple particles were seen in the cornea (corneal chrysiasis) in 5 and in the lens (lens chrysiasis) in 4 patients. Particulate deposits were absent in 11 other RA patients who had not received gold treatment. Seven crystalline lenses from 5 gold-treated patients were removed surgically because of incidental cataract formation and analyzed for gold content using neutron activation analysis. Although the mean lens gold concentration was higher in these patients than in non-gold-treated controls without RA (0.0073 microgram/grams versus 0.001 microgram/grams), the absolute gold level was markedly lower than that found in 25 diverse tissue analyzed previously. This finding is compatible with the absence of clinical gold-related lens disease or visual impairment.

Adult↗

PubMedDate not supplied

Adverse reactions with oral and parenteral gold preparations.

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.

Administration, Oral↗

PubMedDate not supplied

Antecedent tonsillectomy and appendectomy in rheumatoid arthritis.

The prevalence of tonsillectomy and appendectomy was higher in 196 patients with rheumatoid arthritis (RA), prior to the onset of articular disease, than in their spouses and siblings. The estimated increased risk of developing RA with tonsillectomy was 1.5 and 3.5 times, with appendectomy 1.7 and 6.6 times, and with both surgical procedures 2.3 and 6.7 times, using patient-spouse and patient-sibling matched-pair data, respectively. However, only with patient-sibling data did the lower limits of the 95% confidence interval for the risk ratio exceed 1.0. Several hypotheses are offered to explain the possible association between these surgical procedures and RA.

Adult↗

PubMedDate not supplied

Intra-articular corticosteroids. An updated assessment.

Local corticosteroid injections are a relatively safe and effective adjunct in managing rheumatoid arthritis, other connective tissue arthropathies, and soft tissue rheumatism. Rheumatoid synovitis may be suppressed for three months or longer using relatively insoluble microcrystalline preparations. No convincing evidence exists, however, that joint erosive changes are retarded, and steroid injections should be considered ancillary to rest, physical therapy, nonsteroidal anti-inflammatory agents, and disease modifying antirheumatic drugs. The few controlled studies in hip and knee osteoarthritis have demonstrated only modest, fleeting beneficial effects. Nonetheless, clinical experience suggests that intra-articular steroids often ameliorate acute exacerbations of knee osteoarthritis associated with significant effusions, symptomatic involvement of interphalangeal and other nonweight-bearing articulations, synovial cysts, and lumbar facet arthropathy. Judicious use of intrasynovial injections seldom produces significant adverse effects. Iatrogenic infectious arthritis follows one in 14,000-50,000 injections. Rapid acceleration of cartilage attrition is observed rarely. The concept of "corticosteroid arthropathy" is based largely on subprimate animal studies and several anecdotal case reports; limited investigation of primate (monkey) models has shown no significant long-term deleterious effect on cartilage.

Arthritis↗

PubMedDate not supplied

Inhibition of complement by gold sodium thiomalate.

Explore the source record for details and available documents.

Complement Inactivator Proteins↗

PubMedDate not supplied

Comparative pharmacokinetics of parenteral and oral gold compounds.

The pharmacokinetics of intramuscular and oral gold compounds differ widely. Aurothioglucose and gold sodium thiomalate absorption is complete; 25% of auranofin (AF) is absorbed. Blood gold concentrations with conventional parenteral treatment generally peak between 600-800 microgram/dl the day of injection and decline gradually to about 300 micrograms/dl 7 days later. Levels range between 30 and 100 micrograms/dl, using 2-9 mg/d AF, and show little variation. A smaller percentage of gold is found in the cellular fraction of blood with I.M. than with oral gold. The blood half-life is approximately 6 days with gold sodium thiomalate, and 21 days with AF. Forty percent of the administered dose of injectable gold is excreted; depending upon dosage, 75-100% of oral gold is recovered in excreta, which is a combination of unabsorbed and excreted gold. Nearly 70% of parenteral gold is excreted in the urine and 30% in feces, while only 5% of AF is in urine and 95% in feces. The amount of gold retained following intravenous 195Au-labelled gold sodium thiomalate is 43% at 60 days and 25% at 250 days, but only 15% with oral radiolabeled AF 10 days after ingestion. Synovial fluid gold levels are much higher with parenteral than with oral gold but the blood-to-synovial fluid ratio is similar. Skin gold concentrations rise steadily with injectable but not oral treatment, but hair and nail accumulation is insignificant. Corneal, lens, and skin chrysiasis may develop with parenteral therapy, but has not been recognized with AF.

Administration, Oral↗