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Biomedical subjects

K L Blocka

Publications and source records attributed to K L Blocka.

17 recordsLinked to original sources
PubMed2000

Management of corticosteroid-induced osteoporosis.

OBJECTIVES: To educate scientists and health care providers about the effects of corticosteroids on bone, and advise clinicians of the appropriate treatments for patients receiving corticosteroids. METHODS: This review summarizes the pathophysiology of corticosteroid-induced osteoporosis, describes the assessment methods used to evaluate this condition, examines the results of clinical trials of drugs, and explores a practical approach to the management of corticosteroid-induced osteoporosis based on data collected from published articles. RESULTS: Despite our lack of understanding about the biological mechanisms leading to corticosteroid-induced bone loss, effective therapy has been developed. Bisphosphonate therapy is beneficial in both the prevention and treatment of corticosteroid-induced osteoporosis. The data for the bisphosphonates are more compelling than for any other agent. For patients who have been treated but continue to lose bone, hormone replacement therapy, calcitonin, fluoride, or anabolic hormones should be considered. Calcium should be used only as an adjunctive therapy in the treatment or prevention of corticosteroid-induced bone loss and should be administered in combination with other agents. CONCLUSIONS: Bisphosphonates have shown significant treatment benefit and are the agents of choice for both the treatment and prevention of corticosteroid-induced osteoporosis.

Adrenal Cortex Hormones↗
PubMed1993

Familial systemic lupus erythematosus characterized by digital ischemia.

We describe a family in which 3 members each developed systemic lupus erythematosus complicated by ischemic vasculopathy. The calendar years and patient ages of disease onset and the clinical courses were remarkably similar for all 3 patients, although their genotypes were not. The potential contributions of heredity and environment to the concordance of disease expression in this family are discussed.

Adult↗
PubMed1990

Clinical course and predictors of length of stay in hospitalized patients with rheumatoid arthritis.

Patients admitted for therapy of active rheumatoid arthritis were prospectively followed throughout their hospital stay. Average length of stay was 17.1 days. Serial global assessments, whether determined by rheumatologist, physiotherapist or patient appeared to improve linearly until at least hospital day 21. From admission to discharge, mean global assessment scores improved by about one third. Poor global assessment, high disability index, and the presence of comorbid disease and anemia on admission, as well as admission late in the week, were predictive of prolonged hospital stay.

Adult↗
PubMed1988

The effect of age on piroxicam disposition in rheumatoid arthritis.

The disposition of piroxicam in 23 patients with rheumatoid arthritis (9 males, 14 females, aged 27-79) was studied over 6 weeks using the standard oral dose of 20 mg daily. Clinical status was monitored using standard methods. The mean piroxicam steady state plasma concentration (Css) averaged 9.2 +/- 4.4 micrograms/ml, the majority of which was highly protein bound (1.4 +/- 0.5% unbound). Total plasma clearance (CL/F) of piroxicam was 1.85 +/- 0.81 ml/min and the half life (t1/2) was 53.0 +/- 24.2 h. There was wide intersubject variability in the kinetics of piroxicam and its major metabolite 5'-hydroxypiroxicam. Piroxicam CL/F, t1/2 and Css were modestly correlated with patient age. Clinical effects did not appear to be related to piroxicam plasma levels.

Adult↗
PubMed1987

Undiagnosed chronic monarthritis. Clinical and evolutionary profile.

The features and clinical course in 38 patients (25 women, 13 men) who had chronic monarthritis of undetermined origin (UCM) were surveyed over a mean followup period of 24.6 months. At the end of the study, the cause was still unknown in 26 patients (65.7%). In 10 patients, symptoms resolved spontaneously. In the remaining 12 patients, a diagnosis became apparent after a mean period of 17.2 months; diagnoses included spondylarthritis (6 patients), rheumatoid arthritis (3 patients), osteoarthritis (1 patient), erosive arthropathy (1 patient), and glomus tumor (1 patient). Patients in whom a diagnosis emerged were more likely to have positive findings on the following studies: rheumatoid factor (2 of 12); HLA-B27 typing (6 of 11); bone scan, positive over the sacroiliac joint or non-index joint(s) (4 of 6); and roentgenograms of the sacroiliac joint (3 of 8). Findings of these same studies were notably negative in the subgroup of patients with UCM that spontaneously resolved.

Adolescent↗
PubMed1987

Piroxicam and 5'-hydroxypiroxicam kinetics following multiple dose administration of piroxicam.

Piroxicam (20 mg once daily) was administered orally to six healthy young volunteers for 15 days. Trough steady-state levels of piroxicam and 5'-hydroxypiroxicam were 5.5 and 1.2 micrograms/ml, respectively. Piroxicam's plasma half-life (54.9 h) was significantly shorter than that of 5'-hydroxypiroxicam (70.5 h). Percent unbound piroxicam and 5'-hydroxypiroxicam in plasma at steady-state averaged 1.10 and 8.07 respectively. An average of 25.2% of the dose was recovered in urine as 5'-hydroxypiroxicam; approximately two-thirds (17.2%) in the form of the glucuronide conjugate. Average steady-state plasma levels (Css) of piroxicam (7.0 micrograms/ml) were significantly higher than predicted from a previously reported single dose study (5.3 micrograms/ml).

Adult↗
PubMed1986

Clinical pharmacokinetics of piroxicam.

Piroxicam is readily absorbed after oral administration. Food and antacids have been shown not to interfere with its bioavailability. Piroxicam is highly bound (approximately 99%) to plasma proteins and has a small distribution volume (approximately 10 l). Despite its high plasma binding, the drug readily penetrates into synovial fluid. Piroxicam has a long elimination half-life of about 50 h. Elimination of the parent drug is mainly the result of biotransformation. The elimination of piroxicam is impaired in some elderly patients, resulting in a high interindividual variability in average steady state levels following a standard 20 mg/day dosage regimen.

Absorption↗
PubMed1985

Effects of age and sex on piroxicam disposition.

Piroxicam kinetics were studied after a single, oral, 20-mg capsule was taken by 12 young (six women, six men) and 13 elderly (seven women, six men) healthy subjects. Plasma samples were drawn for 216 hr after dosing. Plasma protein binding was studied in vitro by equilibrium dialysis and piroxicam concentrations were measured by HPLC with ultraviolet detection. The apparent volume of distribution was smaller in elderly women (7.8 +/- 0.4 l) than in young men (11.3 +/- 0.3 l) and elderly men (10.8 +/- 0.8 l). There were no such differences when the apparent volume of distribution was normalized for total body weight. There was a strong correlation between total body weight and apparent volume of distribution in all subjects (r = 0.83). Plasma protein binding of piroxicam ranged from 98.90% to 99.54% bound and was not affected by age or sex. Piroxicam body clearance in elderly women (0.026 +/- 0.002 ml/min/kg) was approximately 33% lower than in young women (0.039 +/- 0.003 ml/min/kg). This difference was reflected in different t1/2s of 61.7 and 44.9 hr. Predicted steady-state plasma piroxicam concentrations were 5.7 micrograms/ml in young women, 5.4 micrograms/ml in young men, 5.7 micrograms/ml in elderly men, and 9.3 micrograms/ml in elderly women. The high value in elderly women results from the lower piroxicam body clearance and total body weight. Our data suggest that healthy elderly women eliminate piroxicam at a slower rate than healthy young women. The clinical significance of these data needs to be assessed in patients.

Adult↗
PubMed1984

Outcome assessment in clinical trials. Evidence for the sensitivity of a health status measure.

Health status measures are conceptually relevant to the assessment of clinical outcome in the rheumatic diseases, but their ability to detect meaningful changes in health has not been clearly demonstrated. This report describes the performance of a self-administered health status questionnaire in a randomized, double-blind, 21-week comparison of placebo, oral gold, and injectable gold in rheumatoid arthritis patients. Outcome was assessed by standard clinical measures, including joint count, grip strength, and laboratory tests, and by the Arthritis Impact Measurement Scales, a reliable and valid health status measure that assesses physical disability, psychological status, and pain. Data from the clinical and health status measures produced highly similar conclusions: injectable and oral gold are more effective than placebo for rheumatoid arthritis, and injections are slightly more effective than oral gold. The health status measure was thus quite sensitive to clinically meaningful drug-induced improvements. These findings provide justification for the further application of health status measures to clinical trials of chronic disease.

Chronic Disease↗
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↗
PubMedDate not supplied

Clinical pharmacokinetics of oral and injectable gold compounds.

The pharmacokinetics of oral gold (auranofin) in some respects resemble, and in other respects differ from, those of existing parenteral gold compounds such as gold sodium thiomalate (GST). This may in part relate to physicochemical differences as GST is a water-soluble polymeric compound in vitro whereas auranofin is lipid-soluble and characteristically monomeric. Furthermore, intramuscularly administered gold is greater than 95% bioavailable, whereas only 20 to 30% of an orally administered dose of auranofin is absorbed. Following a standard 50mg intramuscular injection of GST, serum gold concentrations rise sharply, peaking between 4 and 8 mg/L in approximately 2 hours and declining to an average of 3 mg/L by 7 days. With repeated injections of GST stable serum concentrations of gold (3 to 5 mg/L) are eventually achieved (usually within 5 to 8 weeks) although absolute concentrations may vary widely between patients. On the other hand, long term treatment with auranofin is associated with lower and more stable serum concentrations of gold (0.5 to 0.7 mg/L), on the standard dosing regimen of 6 mg daily. Both compounds are retained within the body for prolonged periods. However, the amount of gold retained with auranofin is significantly less compared with GST (less than 5% of a tracer dose of auranofin--about 20% of the absorbed dose--is retained by 100 days whereas the retention for a single labelled dose of GST over a similar interval is greater than 50%). Excretory patterns of GST and auranofin also differ. Most of an absorbed dose of GST (greater than 70%) is excreted by the kidneys whereas only 50% of an absorbed (15% of an administered) dose of auranofin is excreted in the urine. Both compounds are avidly bound by plasma proteins and auranofin shows a particularly strong association with circulating cellular elements. In human subjects, parenterally administered gold is widely distributed among bodily tissues, showing a predilection for tissues of the reticuloendothelial system as well as the kidney and adrenal cortex. Comparable studies in humans are not available for auranofin but animal studies have shown comparatively less affinity for the liver, kidney and spleen. Valuable insight has been gained in analysing the comparative pharmacokinetics of oral and injectable gold compounds. Unfortunately, attempts to correlate pharmacokinetic findings with clinical response or pharmacodynamic changes, as a whole, remain largely unsuccessful with these agents.

Administration, Oral↗