[A few reflexion themes on the method in therapeutic evaluation].
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Biomedical subjects
Publications and source records attributed to G Bouvenot.
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This study was designed to document possible changes in ketoprofen kinetics in female rats related to the stage of the oestrous cycle. At 3 different stages of the oestrous cycle (proestrus, oestrus or dioestrus), 3 different groups of 5 animals each received a single 10 mg/kg intraperitoneal dose of ketoprofen and blood samples were taken at 0.25, 0.5, 0.75, 1, 2, 4, 8, 12 and 24 h after administration. Ketoprofen pharmacokinetic parameters (Cmax, T1/2 alpha and beta, AUC and MRT) were calculated. Our data did not reveal any significant differences in ketoprofen kinetics related to the oestrous cycle.
The best assessment tests for long term trials on osteoarthritis (OA) of the hip and knee are the following, in order of relevance value (consensus of french experts): 1) the loss of joint space thickness on successive radiographies; 2, 3) the indices of the severity for OA of the hip and knee; the investigator's overall opinion; 4) the patient's overall opinion (visual analogue scale of handicap); 5, 6, 7) the pain level (visual analogue scale); the time for going up and down a standard flight of stairs and the time of pain in this distance; the limitation of two articular movements; 8) the increase of either analgesics or NSAIDs consumption; 9) concerning OA of fingers, the number of joints newly involved on successive radiographies. At present, only the radiological tests 1 and 9 are validated. The clinical tests 2 to 8, valuable for short term trials, have yet to be validated for long term follow-up. Recommended duration of trials is three years. A rigorous organisation is necessary to avoid erroneous inclusions: all data recorded in the pre-inclusion visit have to be checked by the principal investigator. Since we have not yet a validated chondroprotective agent as a reference drug, the trial must be randomised, double blind, placebo controlled, parallel group study.
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In order to demonstrate possible modifications of circadian rhythms of plasma proteins in elderly, we measured every four hours during 28 hours in 14 aged (greater than 60 years) subjects orosomucoid, alpha-1-antitrypsin (AAT) and ceruleoplasmin (Cp). A circadian rhythm of the 3 proteins was significantly detected: the 24 hour mean values of orosomucoid and AAT were higher in elderly compared to young subjects but not difference was detected concerning Cp. As far as acrophase and amplitude of these rhythms were concerned no statistical differences were found between elderly and young subjects.
Eleven male subjects were investigated to detect a possible circadian rhythm of the polymorphonuclear phagocytosis. Both cell activity and serum opsonins were studied for numerical detection of granulocytes having ingested at least one particle and for the mean number of ingested particles per cell. No significant temporal differences (ANOVA and cosinor) were found.
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The frequent and severe nosocomial infections in ICU patients suggest that these patients are immunodeficient. We studied the phagocytic activity of granulocytes and monocytes isolated from the blood of 32 ICU patients with nosocomial pneumonia (19 male, 13 female; age 41 +/- 4 yr). Cells were tested in standard medium and in the presence of patients' serum. Blood granulocytes and monocytes were purified and separately exposed to opsonized zymosan (to test C3 receptor function), immunoglobulin-coated erythrocytes (to test Fc receptor function), and glutaraldehyde-treated erythrocytes (to test nonspecific binding structures). Phagocytosis and superoxide anion production were measured. Granulocytes of patients exhibited a substantial decrease of zymosan ingestion (p less than .05), whereas phagocytosis of other particles was normal. Monocytes from the patients displayed an unselective overall decrease of phagocytic ability for the three particle types (p less than .05). Patients' sera were at least as efficient as a pool of normal sera in opsonizing zymosan. Further, no phagocytic inhibitor was found in the tested patients. In conclusion, we point out a deficiency of membrane receptors of neutrophils and monocytes in ICU patients with nosocomial infection.
Determination of urinary delta-amino levulinic acid (ALA) is now systematically used in occupational health to detect an excessive exposure to lead in professionally exposed workers. However, to determine whether circadian changes of the urinary excretion of ALA alter the significance of the test, we quantified the ALA levels in the urine of 19 healthy young adults. Urine samples were taken every 3 hr between 0700 and 2300 hr and ALA levels were determined by a spectrocolorimetric method. The data indicated that the 24-hr mean ALA level was: 1.81 mg/g creatinine. The peak values (2.24 +/- 0.24) were obtained between 1400 and 1700 hr whereas the lowest ALA levels were found between 2200 and 0300 hr. Cosinor analysis revealed a significant circadian rhythm while no significant difference could be found according to sex. Possible explanations of our findings are discussed.
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Circadian rhythms for the factors listed below were investigated in 14 subjects hospitalized in apparently good health: total proteins, albumin, pre-albumin, alpha-1-antitrypsin, orosomucoid, ceruloplasmin, C3, C-reactive protein, haptoglobin and transferrin. Seven venous blood samples were taken from each subject over a 24 hour period. A circadian rhythm was detected for the total proteins, prealbumin, alpha-1-antitrypsin, orosomucoid, ceruloplasmin and transferrin. The acrophases occurred at about 12 hour intervals and the authors research group are already investigating these rhythms for the "inflammation proteins" and the transport proteins in cancer and inflammatory processes.
Changes in total blood cadmium level (CdT), in blood plasma Zinc level (ZnP) and in CdT/ZnP ratio were studied in 39 hypertensive patients compared to 37 healthy subjects. The hypertensive patients were caracterized by a higher CdT level (p less than 10(-5)), a lower ZnP level (p less than 10(-7)) and a higher CdT/ZnP ratio (p less than 10(-7)). A negative correlation was found between CdT and ZnP, and between blood pressure values (systolic and diastolic) and ZnP. A positive correlation was found between blood pressure values and CdT, and therefore CdT/ZnP ratio.
Patients in intensive care units have frequent and severe opportunistic bacterial pneumoniae, even if they were previously free from respiratory disease. A search was made in these patients for possible immune deficiencies. Granulocyte and monocyte phagocytic activities were studied separately in 17 patients with bacterial bronchopneumonia (male: 13, female: 4; age: 41 +/- 5 yr). The ability of three types of particles (opsonized zymosan, immunoglobulin coated and glutaraldehyde-treated sheep red cells) to trigger ingestion was measured. Cells were tested either in normal AB serum or in the presence of patient's serum. A substantial 40% decrease of the fraction of granulocytes ingesting zymosan was found in our experimental conditions (p less than 0.001). Activity with the other particles was not significantly altered. Patients' sera were at least as efficient as a pool of normal sera in opsonizing zymosan. Furthermore, no phagocytic inhibitor was found in the patients tested. Underlying mechanisms for these abnormalities remain unknown, but a better understanding of the aetiology of the altered bactericidal function of phagocytic cells is required before suggesting immunomodulating treatments.