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M Richard

Publications and source records attributed to M Richard.

198 records · Page 11Linked to original sources
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Pharmacokinetics of an indomethacin pro-drug: apyramide after intravenous administration in dog.

The pharmacokinetics of apyramide, an ester of indomethacin and acetaminophen (paracetamol), were determined after intravenous administration to nine beagle dogs. Indomethacin and its pro-drug, apyramide, were extracted from acetonitrile-precipitated plasma by a solvent-demixing procedure and the concentration of these two drugs was measured by a reversed-phase liquid chromatographic assay. The kinetic evolution with time of plasma levels of apyramide and of indomethacin resulting from enzymatic hydrolysis was compared with values obtained for indomethacin injected in equimolar dose. Plasma levels of apyramide quickly decreased and the mean (+/- SD) half life was 0.15 +/- 0.08 h. For metabolic indomethacin, the mean (+/- SD) area under curve was 12.36 +/- 4.80 mg.h/l and the mean (+/- SD) half life of terminal phase was 16.71 +/- 9.46 h. After administration of indomethacin, these values were 17.60 +/- 4.12 mg.h/l and 7.89 +/- 2.20 h, respectively.

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Inhibition of anti-CD3 antibody-induced mouse T cell activation by pentoxifylline in combination with rapamycin or A77 1726 (leflunomide).

Pentoxifylline (PTX), rapamycin (RAP), and leflunomide are potent immunomodulatory drugs with differing modes of action. In order to develop new drug combinations for immunotherapy, we tested the effects of PTX in combination with RAP or A77 1726 (the active metabolite of leflunomide) on in vitro T cell activation in a mouse model system. T lymphocytes in spleen cell preparations were stimulated with anti-CD3 monoclonal antibody alone, or in the presence of PTX (25-200 microg/ml), RAP (0.5-5.0 ng/ml), A77 1726 (2.5-10.0 microM), PTX/RAP (25-200 microg/ml and 0.5-5.0 ng/ml, respectively), or PTX/A77 1726 (25-200 microg/ml and 2.5-10.0 microM, respectively). Anti-CD3-induced T cell proliferation was inhibited in a dose-dependent fashion by the individual drugs. An additive inhibitory effect was observed in cultures treated with PTX/RAP or PTX/A77 1726. The effects of PTX, RAP, A77 1726, PTX/RAP, or PTX/A77 1726 (at concentrations approximating the IC50 of individual drugs for inhibition of lymphoproliferation) on anti-CD3-activated killer (AK) cell induction, CD25 expression, and interleukin (IL)-2 synthesis in anti-CD3-activated spleen cell cultures were also determined. Alone, each drug was able to suppress AK cell induction to varying degrees. PTX plus RAP exhibited strong synergism, while the combination of PTX and A77 1726 had an additive inhibitory effect on AK cell induction. CD25 expression was only weakly inhibited by A77 1726, but the percentage of CD25-expressing cells was greatly reduced in cultures treated with PTX or RAP. The combination of PTX and RAP had an additive inhibitory effect on CD25 expression while PTX and A77 1726 together had an effect equivalent to PTX alone. IL-2 synthesis was inhibited by PTX but was unaffected by RAP or A77 1726. Treatment with PTX plus RAP led to a further reduction in IL-2 production but co-treatment with PTX and A77 1726 approximated the inhibitory effect of PTX alone. We conclude that the combination of PTX and RAP is noteworthy for its potent immunomodulatory activity and may be of use in clinical situations where it is desirable to prevent T cell activation.

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Intracranial hemorrhage after stenting and angioplasty of extracranial carotid stenosis.

BACKGROUND AND PURPOSE: The transluminal angioplasty and stenting procedure has been recently advocated as a potential alternative to surgical endarterectomy for the treatment of severe extracranial carotid stenosis. This study assesses the incidence and significance of intracranial hemorrhage occurring after this procedure. METHODS: We retrospectively reviewed 104 carotid arteries (96 internal, two external, and six common) in 90 patients (63 male; mean age, 69.4 years; range, 48-88 years) who underwent primary stenting and angioplasty by use of Wallstents (103/104) at three centers between January 1996 and January 1999. Seventy-five (83%) patients were referred by neurosurgery departments. Seventy-one (68%) arteries were symptomatic; the mean stenosis percentage was 85% (range, 40-99%). RESULTS: Four intraparenchymal hemorrhages occurred, representing 4.4% of patients and 3.8% of vessels, after angioplasty and stent placement. The mean preoperative stenosis percentage was 95% (range, 90-99%). One hemorrhage occurred immediately after stent placement, whereas the three other hemorrhages occurred in a delayed fashion (mean, 2.8 days). The mean hematoma size was 4.8 cm (range, 2-8 cm). Three patients had associated subarachnoid or intraventricular bleeding; the fourth had associated subdural hemorrhage. Three hemorrhages were fatal; the fourth experienced two seizures only. No acute neurologic symptoms were present prior to hemorrhages, and there was no postprocedural hypertension in these patients. All had been receiving antiplatelet agents as well as intraprocedural IV heparin. CONCLUSION: Intracranial hemorrhage can occur after carotid angioplasty and stenting. We speculate that this represents cerebral hyperperfusion injury. The 3.8% incidence of cerebral hemorrhage observed is approximately sixfold greater than that reported post endarterectomy (0.6%) (95% CI, 0.2-8.7%). This is not statistically significant in this small study group. This trend may reflect patient selection, different anticoagulation protocols, and/or study population size. Additional data are needed to determine the safety and efficiency of carotid stenting as a treatment for carotid stenosis.

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Epidemiological, clinical, biological and radiological differences between atrophic and hypertrophic patterns of hip osteoarthritis: a case-control study.

OBJECTIVE: Lack of osteophytes (atrophic form) has been shown to be a factor in the severity of hip osteoarthritis (OA). The aim of this study was to determine the epidemiological, radiological and biological differences between the hypertrophic and atrophic forms of hip osteoarthritis. METHODS: 25 patients with symptomatic hip OA (ACR criteria) and classified as having an atrophic form of OA based on the lack of osteophytes on standard radiograph of the pelvis, were matched for joint space width with 25 subjects with evidence of the hypertrophic form of hip OA. OA radiological severity was assessed using a scoring system and by computer measurement of the joint space width. Angles of hip dysplasia were measured. Serum hyaluronic acid, cartilage oligomeric matrix protein, collagenase, Type I procollagen, C-terminal crosslinking telopeptide of type I collagen and tissue inhibitor of métalloproteases-1 were assayed by immunoassay and C-reactive protein by ultrasensitive immunonephelemetry. Statistical analysis was performed using logistic regression, taking into account age, sex, body mass index, and bilaterality. RESULTS: Compared to hypertrophic OA, atrophic OA affected chiefly elderly women and was characterized by a smaller centre-edge angle and diffuse superior femoral head migration. It was less frequently bilateral. No statistically significant difference was found in the biological data between the two groups. CONCLUSION: An atrophic bone response in hip OA occurs chiefly in women and is associated with poor coverage of the femoral head. Serum biomarkers able to demonstrate differences between the atrophic and hypertrophic patterns of OA are lacking.

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