PubMed Health⌕ Search

Biomedical subjects

W F Kean

Publications and source records attributed to W F Kean.

At least 19 recordsLinked to original sources
PubMed2004

Osteoarthritis: symptoms, signs and source of pain.

Osteoarthritis is the most common form of arthritis. The condition is characterised by loss or failure of the functional and/or biochemical integrity of the joint. The clinical symptoms include joint stiffness, pain and dysfunction, but the principal problem for the majority of patients is the pain. Although there are no pain receptors in the cartilage, the origin of the pain is thought to be due to stimulation of the A delta mechanoreceptors and the C polymodal nerve endings in the synovium and surrounding tissues. However, some of the pain experienced in and around the joints is referred pain or sympathetic efferent pain. In addition, there is a poor correlation of clinical symptoms with radiological or imaging appearance. This lack of correlation of clinical evaluation and imaging makes attempts at treatment difficult and compromises attempts to design studies and to evaluate the outcome of osteoarthritis in clinical trials.

Clinical Trials as Topic↗
PubMed2001

Nonsteroidal anti-inflammatory drugs: overused or underused in osteoarthritis?

Arthritis and musculoskeletal disorders are common. Arthritis currently accounts for 2% to 3% of all cases of disability, and the numbers are rising. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used, with 75 million prescriptions annually in the United States and 25 million in the United Kingdom. The volume of side effects noted, most of which are gastrointestinal and can be serious, imply the overuse of these drugs, especially in relation to the estimated prevalence of osteoarthritis (OA), where pain relief may be considered more important than an anti-inflammatory effect. There are conflicting data about the efficacy of NSAIDs compared with analgesics alone for pain relief. However, the interpretation of data comparing the two drug classes is limited by shortcomings in research methodologies and by difficulties in incorporating the anti-inflammatory effect of NSAIDs into the outcomes. The efficacy of paracetamol for some patients has been underestimated; however, although those with mild disease may find paracetamol adequate, most patients with OA are likely to gain more benefit from NSAIDs.

Acetaminophen↗
PubMed1997

Auranofin.

Explore the source record for details and available documents.

Adolescent↗
PubMed1994

A comparative study of signal versus aggregate methods of outcome measurement based on the WOMAC Osteoarthritis Index. Western Ontario and McMaster Universities Osteoarthritis Index.

OBJECTIVE: To compare signal versus aggregate measurement strategies using the VA3.0S version of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis (OA) Index. METHODS: Seventy patients with OA of the knee were asked to identify a signal item for each of the 3 dimensions of the WOMAC OA Index at baseline and termination of a 12-week, double blind, randomized, controlled trial. RESULTS: The signal method detected statistically significant alterations in health status at relatively small sample sizes and with a relative efficiency close to or at unity. In addition to a low prevalence of deterioration in nonsignal items, we observed some inconsistency in signal selection. CONCLUSION: Signal methods of measurement may provide an alternative approach to outcome measurement provided issues of nonsignal deterioration and the consistency of signal selection can be addressed.

Aged↗
PubMed1993

Site of action for the inhibition by gold sodium thiomalate of rabbit platelet activation.

The inhibitory action of the gold-based drug gold sodium thiomalate was investigated in rabbit platelets. Gold sodium thiomalate at concentrations of 0.25-13 x 10(-4) M inhibits collagen-, ADP-, and 9,11,dideoxy-11 alpha,9 alpha-epoxymethanoprostaglandin F2 alpha (U46619)-induced aggregation as well as collagen- and U46619-induced serotonin release. This inhibition occurs in both Tyrodes-albumin or Tyrodes-gelatin buffer systems. Preincubation of gold sodium thiomalate with platelets resulted in less inhibition as the time of preincubation increased. The inhibitory effect of gold sodium thiomalate could be removed by washing the platelets. Other sulfhydryl-reacting compounds, such as D-penicillamine, thiomalic acid, 5,5'-dithiobis-2-nitrobenzoic acid, and 6,6'-dithiodinicotinic acid, were all capable of inhibiting collagen-induced aggregation and serotonin release. Evidence is presented that gold sodium thiomalate interferes with the activation of rabbit platelets by several activators, that this action of gold sodium thiomalate is similar to the action of other sulfhydryl-reacting agents, that this inhibition is likely occurring at the membrane, and that the action of the drug is not dependent on the presence of albumin.

Animals↗
PubMed1993

A multicenter study of tenoxicam and diclofenac in patients with osteoarthritis of the knee.

OBJECTIVE: To conduct the first Canadian study of the comparative efficacy and safety of tenoxicam and diclofenac in patients with primary osteoarthritis (OA) of the knee. METHODS: Tenoxicam 20 mg per os once daily (po od) was compared to diclofenac (Voltaren) 50 mg per os 3 times a day (po tid) in a 12-week, double blind, randomized, controlled, multicenter, parallel trial. The primary outcome measure was the pain dimension of the WOMAC OA Index. Following an initial screening visit and a 3 to 7 day NSAID-free washout period (i.e., baseline), patients were assessed at Weeks 2, 4 and 12; assessments including some 15 efficacy variables and safety variables. RESULTS: Ninety-eight patients [tenoxicam (n = 48), diclofenac (n = 50)] participated in the trial. Statistically significant (p < or = 0.05) improvements in all 3 dimensions of the WOMAC OA Index and six efficacy variables were noted in both treatment groups. No significant between drug differences were noted on any efficacy variable. Significantly fewer patients reported adverse events in the tenoxicam group (21 vs 33, p = 0.03). CONCLUSION: Tenoxicam is efficacious and well tolerated in patients with OA of the knee. In this group of patients it was similar in efficacy and superior in tolerability to diclofenac 150 mg/day (50 mg tid). Thus the benefit/risk ratio of tenoxicam was superior to that of diclofenac in this study.

Aged↗
PubMed1992

The pharmacokinetics of flurbiprofen in younger and elderly patients with rheumatoid arthritis.

The pharmacokinetics of flurbiprofen (Ansaid Tablets, Upjohn Company of Canada, Don Mills, Ontario) were evaluated in both younger (40 to 60 years) and elderly (65 to 83 years) rheumatoid arthritic patients after both a 100-mg single-dose administration and at steady state during a 100-mg twice-a-day dosage regimen. Both flurbiprofen plasma concentration-time profiles and the urinary excretion of flurbiprofen and its major metabolites were evaluated. The results indicate that the pharmacokinetics of flurbiprofen are linear in both age groups based on only minor changes between single-dose and steady-state parameter determinations and the agreement between calculated and predicted accumulation values in plasma concentrations. Only minor differences in the pharmacokinetic parameters were observed between the younger and elderly patients. Only free flurbiprofen clearance was found to have a significant but variable correlation to patient age. The effect of flurbiprofen on the urinary excretion of two prostaglandins were also evaluated throughout this study. In both age groups, the maximum decrease in urinary excretion was observed after the first dose, and this effect was maintained throughout the remainder of the study. Percent decreases from baseline in urinary excretion during drug administration were similar for both age groups. Similar side-effect profiles were observed between age groups.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Double blind randomized controlled trial of sodium meclofenamate (Meclomen) and diclofenac sodium (Voltaren): post validation reapplication of the WOMAC Osteoarthritis Index.

Following several years of development and validation, we applied the WOMAC Osteoarthritis Index as the principal outcome measure in a double blind randomized parallel trial of Meclomen (100 mg po tid) and Voltaren (25 mg po tid). Statistically significant improvements in clinical status were noted in both treatment groups. At the doses studied, between drug differences favoring Meclomen were observed in pain and stiffness, no difference being noted in physical function. No significant between drug difference was noted in tolerability at these same doses. Our study also demonstrated that the relative efficiency of WOMAC was similar to that of the Lequesne and Doyle indices. Finally, we defined the standard deviation necessary to calculate sample size for future studies using the WOMAC index, both for studies based on static scores and those based on change scores.

Adult↗
PubMed1992

Osteoarthritis antirheumatic drug trials. I. Effects of standardization procedures on observer dependent outcome measures.

We designed a study to assess the effects of standardization procedures on reducing interobserver variability for outcome measures given in the current Food and Drug Administration and European League Against Rheumatism guidelines and others selected from the rheumatology literature. Over 2 days, 6 rheumatologists independently examined 6 patients with osteoarthritis (OA) in predetermined order before and after standardizing their examination techniques. An important and beneficial effect of the standardization procedure was observed on the majority of outcome variables. Such reductions in observer variability have the potential to diminish sample size requirements for OA antirheumatic drug studies.

Adult↗
PubMed1992

Osteoarthritis antirheumatic drug trials. II. Tables for calculating sample size for clinical trials.

The calculation of sample size for clinical trials requires knowledge of the standard deviation (SD) of index variables. There are no published lists of SD and it is difficult to locate variance estimates based on relevant populations. In this study we used standardized procedures to determine in 60 patients with osteoarthritis (OA) of the knee the standard deviation of key outcome measures recommended in current Food and Drug Administration and European League Against Rheumatism guidelines for OA clinical trials. These tables will be useful to clinical researchers in selecting outcome measures as well as for calculating sample size requirements for future clinical studies in OA.

Clinical Trials as Topic↗
PubMed1992

Osteoarthritis antirheumatic drug trials. III. Setting the delta for clinical trials--results of a consensus development (Delphi) exercise.

Defining the minimum clinically important difference or delta to be detected in a clinical trial depends on a number of factors including the research hypothesis, patient characteristics, the nature of the intervention and the trial design. In 2 studies, we have developed standardized procedures for conducting outcome measurement based on current Food and Drug Administration and European League Against Rheumatism guidelines for osteoarthritis clinical trials, and determined the standard deviation for these outcome measures. In the final component of this series of studies, we have used a Delphi technique to establish estimates for delta, and calculated the sample size requirements under 2 different conditions of Type I and Type II error probabilities.

Clinical Trials as Topic↗
PubMed1991

Action of gold sodium thiomalate on experimental thrombosis in vivo.

In order to study the effect of gold compounds on the action of thrombin in vivo, experiments were performed to measure platelet survival and the weight of thrombus formation in experimental models of intra-aortic thrombosis by two indwelling aortic catheter methods. We have called these the long and short catheter methods. Platelet survival was reduced in all gold-treated and control animals which had indwelling aortic catheters. In the long catheter model, New Zealand White male rabbits were treated with one of the following: gold sodium thiomalate, sterile water, gold thioglucose, gold sodium thiosulfate, disodium thiomalate. Gold sodium thiomalate-treated rabbits had a reduced weight of experimentally induced intra-aortic thrombi compared with animals treated with sterile water or equimolar concentrations of gold thioglucose, gold sodium thiosulfate, or disodium thiomalate. This reduction in thrombus weight in the animals treated with gold sodium thiomalate was not reflected by changes in platelet survival or fibrinolysis. The serum gold levels achieved in these in vivo experiments was in the range of 5.0 X 10(-5) to 1.0 X 10(-4) M. These values are comparable to levels which can be achieved in human subjects immediately after a gold injection. In the short catheter model, New Zealand White male rabbits were treated with either gold sodium thiomalate, gold thioglucose, disodium thiomalate, or auranofin. Controls were given either water or 0.05% chlorocresol. Water-treated and gold sodium thiomalate-treated animals were also given 51Cr-labeled platelets and 125I-fibrinogen before insertion of the catheter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Clinical evaluation of a sustained release compared to a standard formulation of tiaprofenic acid (Surgam) in rheumatoid arthritis: a Canadian multicenter study.

A double blind, randomized, parallel group clinical therapeutic trial, comparing a sustained release formulation with a standard preparation of tiaprofenic acid (Surgam), was performed in 119 patients with rheumatoid arthritis. The sustained release preparation was prescribed as two 300 mg capsules taken once a day, and the standard formulation as one tablet of 300 mg taken twice a day. From baseline up to the 3rd and 6th week of treatment, a statistically significant difference (p less than 0.001) was observed in both treatment groups for all the variables, indicating objective or subjective changes in the clinical signs and symptoms of the patients. For most of these variables, no significant differences were observed between the sustained release and the standard formulations. Also, no significant differences were observed between the 2 formulations in the incidence of side effects and abnormal laboratory findings.

Adult↗