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Biomedical subjects

R G Pietrusko

Publications and source records attributed to R G Pietrusko.

13 recordsLinked to original sources
PubMed1988

An open study of auranofin in the treatment of steroid-dependent asthma.

To determine the efficacy of oral gold in asthma, 20 patients with steroid-dependent asthma received auranofin at a dose of 3 mg by mouth, twice daily, in a 24-week open clinical trial. Prospective evaluation of bronchial responsiveness to methacholine was determined before and 8 and 16 weeks after initiation of auranofin therapy. Serial spirometry (FEV1 and FVC), lung volumes, and diffusing capacities (single breath carbon monoxide diffusing capacity of the lungs) were measured before and at 10 and 20 weeks after treatment. All subjects were required to record concomitant medications, symptom scores, and morning and evening peak expiratory flow rates. In vitro immunologic studies performed before and after 8 and 20 weeks of auranofin therapy included leukocyte histamine release in response to antihuman IgE, lymphocyte blast transformation in response to concanavalin A and phytohemagglutinin, and leukocyte inhibitory factor activity in response to Candida albicans and tetanus toxoid antigens. In 18 patients evaluated, there were no significant differences between baseline and posttreatment spirometry, single breath carbon monoxide diffusing capacity of the lungs, and lung volumes. At week 16 of treatment, the steroid cumulative dose or the total prednisone dose administered from 7 days before through 10 days after each methacholine test day decreased from a mean of 293 +/- 125 mg at baseline to 192 +/- 115 mg. At week 16, nine of 18 patients (50%) exhibited decreased methacholine responsiveness as defined by a more than one-half log10 increase in the concentration of methacholine causing a 20% decrease in FEV1. A significant correlation (r = 0.60) was observed between the increase in the concentration of methacholine causing a 20% decrease in FEV1 and the decrease in steroid cumulative dose after 16 weeks of treatment. Leukocyte histamine release to anti-IgE exhibited significant reductions from baseline at week 20 to 10(-2) (p less than 0.002) and at 10(-3) (p less than 0.005) dilutions. At week 20, leukocyte inhibitory factor activity in response to Candida increased from baseline at the 0.1 mg per well (p = 0.025) and 1 mg per well (p = 0.05) concentrations; similarly, the responses to tetanus toxoid increased at the 1 mg per well (p less than 0.05) and 0.1 mg per well (p less than 0.01) concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1986

Long-term efficacy and safety of auranofin: a review of clinical experience.

Auranofin (AF) is the first oral gold therapy developed for the treatment of rheumatoid arthritis (RA). Since the drug was introduced in 1982, more than 100,000 patients have been treated with AF. Controlled clinical trials prior to introduction included more than 5,000 patients, some of whom received AF for more than 7 years. At the recommended dose of 6 mg/day, AF therapy results in a lower total body burden of gold than does injectable gold (IG). However, comparative studies indicate that the clinical effect of AF is comparable to that of IG. Adverse events that occur during AF therapy tend to be mild and of short duration, often resolving with continued therapy or temporarily reduced dosage. Most adverse events occur during the first few months of therapy, and the incidence diminishes over time. Data on 134 patients who received AF for more than 5 years demonstrate a sustained therapeutic effect and no cumulative toxicity from long-term therapy. In 18 comparative trials, 1,053 patients with RA received either AF (527 patients) or IG (526 patients) for up to 36 months. At 1 year, similar proportions of patients in the AF and IG groups had 50% or greater improvement in various parameters of disease activity. Safety analysis showed that AF was significantly better tolerated than IG. The rate of withdrawal because of adverse events was about twice as great in the IG group as in the AF group, both at one year (14% vs. 31%, p less than 0.05) and for the duration of the trials (18% vs. 34%, p less than 0.05). This suggests that the benefit-to-risk ratio is more favorable with AF.

Administration, Oral↗
PubMed1985

An analysis of worldwide safety experience with auranofin.

A total of 3,475 patients with rheumatoid arthritis have received auranofin (AF) during clinical trials in 27 countries. Over a 4-year period, treatment with AF was relatively well tolerated. Most reactions were mild, easily managed and occurred during the first few months of treatment. Gastrointestinal side effects were the most common problems reported with AF followed by mucocutaneous reactions. Less frequently observed were conjunctivitis, proteinuria and, rarely, thrombocytopenia. The percentage of patients withdrawn for adverse effects per patient-year was less with AF when compared to injectable gold (14 vs 40%). These results confirm previous reports of AF safety and improved tolerance versus parenteral gold.

Actuarial Analysis↗
PubMed1984

Auranofin: a unique oral chrysotherapeutic agent.

Auranofin is a chemically unique gold coordination complex with demonstrated antiarthritic properties on oral administration. Its pharmacokinetic and immunologic profiles are distinct from injectable gold compounds. When auranofin is added to a regimen of salicylates and/or a nonsteroidal antiinflammatory drug for the treatment of RA, significant additional therapeutic benefit is observed. Published studies indicate that auranofin given 6 mg per day approaches the efficacy of parenteral gold salts in the treatment of rheumatoid disease. Noticeable improvement in clinical and laboratory parameters of disease activity has been observed by the third month of auranofin therapy. Further benefit occurs in some patients during the remainder of the first year of treatment. In the more than 3,000 patients treated with auranofin, the most frequently reported side effects were gastrointestinal (mainly diarrhea) and mucocutaneous. Most side effects were mild in nature and the withdrawal rate due to all adverse reactions averaged 11%. Auranofin differs from injectable gold by producing more gastrointestinal but fewer mucocutaneous reactions. The severity of these reactions is less with auranofin and causes fewer withdrawals from therapy.

Anti-Inflammatory Agents↗
PubMed1984

Proteinuria in gold-treated rheumatoid arthritis.

Treatment records of 1800 patients with rheumatoid arthritis who were included in the clinical trials of auranofin in the United States were examined for data on development of proteinuria. Three percent (41) of 1283 auranofin-treated patients had an abnormal 24-hour urine protein level: 15 had mild (0.15 to 1 g/d), 17 had moderate (1 to 3.5 g/d), and 9 had heavy (greater than 3.5 g/d) proteinuria. Permanent renal impairment did not occur, and proteinuria did not persist beyond 12 months in most patients. Seven of eight patients who were rechallenged when the proteinuria had cleared were able to continue treatment without relapse. No clinically discernible risk factors were found. Biopsy specimens from 4 patients showed membranous glomerulonephritis, which indicates an underlying immunopathologic mechanism. In similar groups of patients, the risk of developing proteinuria with auranofin therapy is significantly less than that with parenteral gold therapy (p less than 0.05) and similar to that with background therapy with nonsteroidal antiinflammatory drugs (p = 0.92). The lower incidence and relatively benign nature of proteinuria seen in this review support previous findings that auranofin is better tolerated than injectable gold.

Adult↗
PubMed1979

Drug therapy reviews: pharmacotherapy of diarrhea.

Gastrointestinal physiology, and the pathophysiology, diagnosis, symptoms and treatment of acute and chronic diarrhea are reviewed. Drugs used in the treatment of diarrhea include opiates (morphine, codeine), synthetic anti-diarrheals (diphenoxylate, loperamide), anticholinergics (atropine, propantheline), adsorbents (kaolin, pectin, cholestyramine resin) and Lactobacillus acidophilus. Chronic diarrhea and acute diarrhea caused by microorgansims, drugs and viruses are described. The management of diarrhea can be divided into three categories: (1) supportive therapy (fluid and electrolyte replacement); (2) symptomatic therapy which improves the consistency of the stool and reduces the frequency of bowel movements; and (3) specific therapy aimed at treating the cause (e.g., antibiotics for bacteria-induced diarrhea) or blocking the cellular mechanisms of fluid and electrolyte loss. Most acute diarrheal conditions can be managed successfully by avoiding oral solids and ingesting carbohydrate-electrolyte solutions. Synthetic antidiarrheals may increase the toxicity associated with bacterial diahhrea.

Adsorption↗
PubMed1978

Pit viper snakebite in the United States.

Pit viper snakebite is a relatively uncommon medical emergency which must be adequately diagnosed and treated to minimize local tissue destruction and systemic complications and to prevent death. Severity is highly variable and may range from minimal local pain and swelling to marked pain, edema, tissue necrosis, hemorrhage, shock, and death within one hour. By far, the most common complication is local tissue destruction often resulting in loss of function. Pit viper venom is extremely complex, containing factors which directly destroy muscle, blood vessels, and renal tissues. Other components anticoagulate blood and cause hypotension, local edema, and pain. Neurotoxicity is unusual, but respiratory paralysis may follow Mojave rattlesnake bites. Proper first aid consists of a proximal mildly constricting tourniquet, superficial incision at fang marks, and constant suction. Medical management consists of early intravenous antivenin in adequate dosage, after hypersensitivity testing. Other measures are largely supportive. The early use of corticosteroids is controversial. Cryotherapy is to be avoided. Fasciotomy may be necessary when edema is severe and impairs arterial perfusion. Promising developments include immunization trials against pit viper venom as well as studies on the antivenom activity of rattlesnake plasma.

Adrenal Cortex Hormones↗
PubMed1977

Use and abuse of laxatives.

Colon physiology, the causes of constipation, an approach to management of constipation, and the features of various laxatives are reviewed. The categories of individual agents discussed include the bulk-forming laxatives, stimulant cathartics, saline laxatives, hyperosmotic laxatives, surfactant laxatives, emollient laxatives, enemas and suppositories. Dietary change and attention to proper bowel habits are frequently the only therapy necessary for the treatment of constipation. When laxative intervention is necessary, one of the milder agents should be employed over a short period of time. The chronic abuse of stimulant cathartics, often deeply rooted in family or ethnic traditions, is a significant problem and difficult to treat.

Cathartics↗