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Biomedical subjects

W F Kean

Publications and source records attributed to W F Kean.

At least 37 records · Page 2Linked to original sources
PubMed1991

Ankylosing spondylitis 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 Drug Administration and European League Against Rheumatism guidelines and others selected from the rheumatology literature. Over 2 days, 6 rheumatologists independently examined 7 patients with ankylosing spondylitis (AS) 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 AS antirheumatic drug studies.

Adult↗
PubMed1991

Ankylosing spondylitis antirheumatic drug trials. II. Tables for calculating sample size for clinical trials.

The calculation of sample size requires knowledge of the standard deviation (SD) of index variables. Unfortunately, there are no published lists of standard deviations and it is exceedingly difficult to locate variance estimates based on relevant populations. We used standardized procedures to determine in 60 patients with ankylosing spondylitis (AS) the SD of key outcome measures recommended in current Food Drug Administration and European League Against Rheumatism guidelines for AS clinical trials. We anticipate that 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 AS.

Analysis of Variance↗
PubMed1991

Ankylosing spondylitis antirheumatic drug trials. III. Setting the delta for clinical trials of antirheumatic drugs--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 previous studies, we have developed standardized procedures for conducting outcome measurement based on current Food and Drug Administration and European League Against Rheumatism guidelines for clinical trials in ankylosing spondylitis, and thereafter, determined the standard deviation for these outcome measures. In the final component of this series of studies, we have employed 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.

Anti-Inflammatory Agents↗
PubMed1990

A controlled comparison of piroxicam and diclofenac in patients with osteoarthritis.

Eighty patients with osteoarthritis were randomly assigned to either piroxicam (20 mg daily) or diclofenac (75-150 mg daily) in a 12-week double-blind, parallel groups study. In the 70 patients who completed the study, both medications were effective; statistically significant improvement was observed on all assessments of efficacy. However, no statistically significant differences between the two drugs were seen on any of the efficacy parameters measured. There was a trend towards better tolerance in the piroxicam treated patients, although this was not statistically significant; 3 of the 40 piroxicam treated patients versus 6 of the 40 patients on diclofenac were discontinued from the trial due to intolerable adverse events.

Activities of Daily Living↗
PubMed1990

Pregnancy and rheumatoid disease.

The onset of pregnancy appears to result in the amelioration of rheumatoid disease activity. This is most likely to be related to the change in hormonal, and thus immunological, status of the mother. Spontaneous abortion appears to be increased in mothers with rheumatoid disease. Whether this is due to disease status or to drug therapy is not entirely clear for all cases, but there is a suggestion that it could be the disease state. If at all possible, drugs should be avoided during pregnancy but simple anti-inflammatory drugs in low dosage probably do not produce any major problems. Immunosuppressant drugs should be avoided at all times except when the mother's health is at serious risk. The continued use of disease remitting agents throughout pregnancy is probably not necessary and there is still sufficient question as to whether these drugs could be potentially toxic to the infant. Primum non nocere.

Arthritis↗
PubMed1989

Effect of R and S enantiomers of naproxen on aggregation and thromboxane production in human platelets.

The effects of R and S enantiomers of naproxen [(+)-6-methoxy-alpha-methyl- 2-naphthaleneacetic acid] were studied on platelet aggregation and on the production of thromboxane B2 from collagen-stimulated human platelets in order to determine the effect of each enantiomer in terms of cyclooxygenase inhibition. S-Naproxen caused inhibition of platelet aggregation in platelet-rich plasma and washed human platelets in a concentration-related fashion in the range 1-80 micrograms/L. A similar concentration-related suppression was noted for R-naproxen, but this inhibition was significantly less than that induced by S-naproxen for all concentrations except 1 micrograms/L. Similarly, both R- and S-naproxen (1-80 micrograms/L) caused a concentration-dependent suppression of thromboxane B2 production from platelet-rich plasma. These values were significant at all concentrations of drug (10-80 micrograms/L) except at 1 micrograms/L. Significant differences in thromboxane B2 production from washed human platelets were noted at concentrations of 10 and 25 micrograms/L. The findings support previous studies reported in the literature that S-naproxen is more active than R-naproxen. Our findings that S-naproxen is more active than R-naproxen on collagen-stimulated platelet aggregation and prostaglandin production suggest that the findings of greater activity of S isomer over the R isomer in animal models of inflammation may be a direct expression of the differential action on prostaglandin synthesis.

Collagen↗
PubMed1989

Measurement of pain threshold in patients with rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and healthy controls.

Pain threshold was measured using a pressure algometer in 126 subjects, of whom 54 were females and 72 males. These subjects included 18 males and 18 females with rheumatoid arthritis, 18 males and 18 females with osteoarthritis, 18 males with ankylosing spondylitis, and 18 male and 18 female healthy control volunteers. Six points were studied on each side of the body: 2 cm above the eyebrow on the forehead, lateral aspect of the arm at the insertion of the deltoid muscle, midpoint of the ulna, hypothenar eminence in the palm, midpoint of the quadriceps muscle, and midpoint of the antero-medial aspect of the tibia. None of these points corresponded to the "trigger" points in fibromyalgia. The pain threshold was statistically significantly higher in patients with ankylosing spondylitis than in patients with osteoarthritis, and these in turn were statistically higher than in the normal subjects. Patients with rheumatoid arthritis had significantly lower pain thresholds than the normal subjects. No laterality in pain threshold was identified, but females had in general a lower pain threshold.

Adult↗
PubMed1988

Biological action of colorless and yellow solutions of gold sodium thiomalate on thrombin activity and the mixed lymphocyte reaction.

Gold sodium thiomalate is a pale yellow powder which forms a colorless solution when added to sterile water. The marketed form of gold sodium thiomalate is a pale yellow solution. The yellow color develops as a result of the sterilization process. This study demonstrates that the physical change induced in the drug by the sterilization process has no effect on the action of gold sodium thiomalate on the serine esterase thrombin, nor on the inhibition of the mixed lymphocyte response. Thus it is unlikely that the yellow component is responsible for benefit in rheumatoid arthritis. If the components creating the yellow color cause toxicity, the preparation and/or formulation of the drug should be changed.

Blood Platelets↗
PubMed1987

The contribution of William Hunter (1718-1783) to the study of bone and joint disease.

William Hunter (1718-1783), the elder of the two famous Hunter brothers, is best known for his remarkable book The Anatomy to the Human Gravid Uterus, and for his contributions to the art of midwifery. However, Hunter also made significant observations in cardiovascular disease, in comparative anatomy, and paleopathology. It is perhaps not sufficiently known that he also made significant contributions in rheumatic disease, and in particular, the anatomy and physiology of cartilage.

Bone Diseases↗
PubMed1987

Gold induced thrombocytopenia: 12 cases and a review of the literature.

Gold induced thrombocytopenia is immune mediated, with the production of platelet associated IgG leading to peripheral platelet destruction. An association with HLA-DR3 has been demonstrated. Corticosteroid therapy is effective in treatment, although other modes of therapy may be as efficacious.

Arthritis, Rheumatoid↗
PubMed1987

Variation in physical and biological properties of solid gold sodium thiomalate on dissolution: an electron microscopic and energy dispersive spectroscopic study.

The dissolution of solid gold sodium thiomalate (GSTM) in water results in loss of yellow color. We studied the initial reaction on dissolution. It was associated with the disappearance of 2 absorption peaks on ultraviolet spectrum, one a well defined peak at 335 nm and the other a shoulder at 370 nm. This solution caused platelet aggregation and on transmission electron microscopy, dense gold containing particles measuring 125 nm are seen. Within 10 min of onset of dissolution, no gold containing particulate matter was detectable on electron microscopy. By 20 min, fibrillar particles measuring 40-150 nm appear. These resembled in general morphology and element composition the particles seen within aurosomes in platelets treated with Myochrysine (GSTM) and in synovium and other tissues by other workers. Our data elaborate on previous physical and chemical studies and correlate with morphological variations of gold containing particles at different phases. These variations in GSTM may be due to polymer size and/or structural change within the polymer. The biochemical significance of our data should provide better understanding of the biological effects of these gold thiol compounds in vivo.

Blood Platelets↗