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Biomedical subjects

A Lussier

Publications and source records attributed to A Lussier.

At least 19 recordsLinked to original sources

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

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

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

Crystal-induced neutrophil activation. I. Initiation and modulation of calcium mobilization and superoxide production by microcrystals.

The effects of monosodium urate and calcium pyrophosphate dihydrate crystals on the levels of cytoplasmic free calcium and on the oxidative burst in normal human blood neutrophils were examined. The pattern of sensitivity to granulocyte-macrophage colony-stimulating factor, colchicine, cytochalasin B, pertussis toxin, diglyceride kinase, and protein kinase C inhibitors differentiated the mechanism(s) of neutrophil activation by the crystals from that involved in the responses to soluble chemotactic factors and indicated that individual crystals can use several activation pathways.

Alkaloids

Crystal-neutrophil interactions lead to interleukin-1 synthesis.

Normal human blood neutrophils were studied for their capacity to synthesize and release interleukin-1 (IL-1) species after phagocytosis of triclinic monosodium urate (MSU) and calcium pyrophosphate dihydrate crystals (CPPD). MSU crystals were more potent inducers of IL-1 generation than CPPD or unopsonized zymosan. Microcrystal-stimulated neutrophils characteristically secreted most of the newly synthesized IL-1. Colchicine partly inhibited the secretion of IL-1 by neutrophils during phagocytosis of solid particles. However, colchicine selectively inhibited IL-1 synthesis induced by microcrystals. These results suggest that neutrophil-derived IL-1 may contribute to the pathogenesis of crystal-induced arthritis.

Calcium Pyrophosphate

The search for common ground: a critique.

The paper discusses the positive and the negative sides of the common ground perspectives as proposed at the Montreal and Rome Congresses. Freud is the origin of the guardian role of the IPA, but the time is over when one man or one small group could dictate what psychoanalysis is and should be. This task has become an ongoing challenge for the total group. Psychoanalysis has to avoid becoming a fourre-tout as well as avoiding being ruled by any sort of dictatorial credo. One ideal way to deal with the unavoidable basic divergences is what Roy Schafer has called comparative psychoanalysis, where each new approach is evaluated in respect to the existing fundamental principles; in the long run, the irrelevant views would fade away. In the second part, the author gives his own idea about the irreducible principles that should define essential psychoanalysis.

Forecasting

Gastrointestinal microbleeding after aspirin and naproxen.

Gastrointestinal bleeding is the most serious side effect encountered with the anti-inflammatory antirheumatic drugs. Using the 51Cr labeling technique, the comparative quantity of blood loss with aspirin or naproxen has been previously done on normal volunteers. With the present study, 12 rheumatoid arthritic patients were controlled in a double-blind crossover study with the same radioactive technique. There is a difference in favor of naproxen. The difference between the baseline period and naproxen administration was not statistically significant.

Adult

Inhibition of adjuvant-induced arthritis in the hyperuricemic rat.

In man, there is a strong negative correlation between gout and rheumatoid arthritis. To investigate this apparent mutual exclusion, we studied the influence of oxonate-induced hyperuricemia on the development of adjuvant arthritis in male Wistar rats. The results indicate that in the primary reaction (inflammation of the injected paw) the differences are weak (0.10 greater than p greater than 0.05) between normouricemic and hyperuricemic rats. In hyperuricemic rats the secondary reaction (induced polyarthritis) is delayed and significantly reduced (p less than 0.005). Non-immunologic carrageenin paw edema is not statistically different between the two groups (p greater than 0.25). Experimental hyperuricemia in rats seems to influence essentially the secondary, cell mediated, reaction without affecting the acute inflammatory phases.

Animals

Naproxen vs. aspirin in osteoarthritis of the hip and knee.

This 12-week double-blind trial compared the efficacy and tolerance of naproxen (750 mg/day) with that of aspirin (3.6 gm/day). There was no statistical difference in efficacy between the two trial drugs for any of the objective (e.g., 25-foot walking time) or subjective (e.g., overall severity of symptoms) variables measured. No side effects were experienced by 69% of the naproxen patients and 37.5% of the aspirin patients. There were a statistically greater number and more severe side effects during aspirin therapy than during naproxen therapy (p = 0.002). The results show naproxen to be a potentially useful drug for the treatment of osteoarthritis.

Adult

Inhibition of adjuvant arthritis in the rat by an oxonate diet: sequential studies.

To study the mechanism by which oxonate-induced hyperuricemia inhibits the development of adjuvant arthritis in the rat, we initiated blocking or releasing experiments by changing the oxonate diet of rats at selected times. We were able to define oxonate dietary effects on four specific periods in the development of this experimental arthritis. The inhibition of the primary inflammation at the site of the injection was weak. The inhibition of the secondary reaction was greater than the decrease of the primary inflammation and was more effective when the first two periods (sensitization to antigen and production of immunocompetent cells) were blocked. The reduction in the disease was more marked in the non-injected paw than in the injected paw. Thus, the effect of the oxonate diet is more immunosuppressive than anti-inflammatory. Release of the first period, which provoked an unexpected increase in the severity of the disease, suggests a possible influence of oxonate on pyrimidine metabolism.

Animals

[An unusual dissecting cyst of the knee in a patient with rheumatoid arthritis].

An unusual synovial cyst of the knee in rheumatoid arthritis is reported. The communication with the knee joint anteriorly under the tibial insertion of the internal collateral ligament is in contrast with all the cases reported to date in the literature. The advantages of the air arthrogram (coupled with the arteriography) over the opaque contrast medium arthrography are shown to be superior for such special case.

Arthritis, Rheumatoid

Gastro-intestinal microbleeding under acetylsalicylic acid, ketoprofen and placebo.

A quantitative comparison of gastro-intestinal microbleeding induced by acetylsalicylic acid (ASA), 3.6 g daily, ketoprofen (KETO), 200 mg daily and placebo (P) was undertaken in 12 normal volunteers using a double-blind factorial design with repeated measures. We conclude that KETO induces less gastro-intestinal bleeding than ASA but more than placebo and that there is a significant residual bleeding under placebo following ASA.

Anti-Inflammatory Agents

Gastrointestinal microbleeding in normal subjects receiving acetylsalicylic acid, placebo, and R-803, a new antiinflammatory agent, in a design balanced for residual effects.

This study was undertaken to compare the relative gastrointestinal toxicity of equipotent doses of acetylsalicylic acid (ASA), 900 MG q.i.d., and a new anti-inflammatory agent, R-803, 300 mg q.i.d., against placebo. Gastrointestinal micro-bleeding was quantitated with the 61Cr-labeled erythrocyte assay. The experimental design was balanced for residual effects in the first week following any treatment. An interesting relationship between stool weight and blood loss was found to influence the microbleeding independently of the treatments themselves. All observed blood loss values were corrected by regression to a reference stool weight of 100 Gm. Final analysis of corrected values was done on arithmetic and logarithmic scales. On both scales, R-803 induced much less blood loss than ASA. A difference of 1.3 ml/day between R-803 and placebo was not statistically significant on the arithmetic scale. On the log scale, a statistically significant difference was found; but since it corresponds to 0.4 ml/day, it was not considered to be clinically significant at this dosage.

Anti-Inflammatory Agents