[Incidence of thromboembolism depending on the type of surgery].
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
H Decousus
Publications and source records attributed to H Decousus.
[Chronopharmacology of fractionated heparin (nadroparin) administrated by subcutaneous route at prophylactic doses in healthy volunteers].
This study evaluated the effect of injection time on pharmacodynamic of a single subcutaneous bolus of nadroparine (7500 anti-Xa IC U) evaluated by anti-Xa activity (Hepaclot and Heptest) and by activated partial thromboplastin time (APTT by auto PTT reagent). 10 healthy male volunteers were studied at 4 different 24 hours periods with 4 different injection times (6 am, 12 am, 6 pm, 12 pm) and with a one week wash-out period between each period. No chronopharmacological variation of the anti-Xa activity evaluated by Hepaclot was found. However the anti-Xa activity evaluated by Heptest was higher at the sixth hour after 12 am injection (p = 0.0022). No difference on APTT values was observed whatever the injection time. So the injection time of nadroparine has a weak influence on anti-Xa activity and no effect on APTT; Before to conclude on the lack of chronopharmacological effect of nadroparine, it seems necessary to evaluate such a possibility with higher dosage, with sick and older subjects.
Adult↗
Intravenous prostacyclin in thrombotic thrombocytopenic purpura: case report and review of the literature.
The use of prostacyclin infusion in thrombotic thrombocytopenic purpura is consistent with the hypothesis that patients may lack a plasma factor stimulating prostacyclin production. However, prostacyclin therapy, alone or in combination with aspirin, dipyridamole, steroid and plasmapheresis, failed in many cases. We here describe the case of a patient who responded dramatically to a combination of prostacyclin and plasma infusions, after conventional therapy had failed (plasmapheresis, fresh frozen plasma infusions). Prostacyclin was infused intravenously initially for 120 h from 4 to 9 ng kg min-1 and then continuously for 48 h at 9 ng kg min-1. Despite the scarcity of case reports in the literature, we conclude that the failure of prostacyclin in thrombotic thrombocytopenic purpura appears to be related to insufficient doses and/or duration of therapy.
Adult↗
Circadian dynamics of coagulation and chronopathology of cardiovascular and cerebrovascular events. Future therapeutic implications for the treatment of these disorders?
Arterial thromboembolic disorders are the leading cause of death in most of the advanced nations. The study of epidemiologic relationship of these disorders to biological rhythms may lead to a better understanding and perhaps a better treatment. Chronoepidemiologic studies demonstrated a morning peak for arterial thromboembolic disorders (cerebral and myocardial infarctions) and sudden cardiac deaths. These variations might be explained partially by circadian variations in hemostasis. Indeed chronophysiologic studies have shown that hemostatic variables follow circadian rhythms. The level of platelet aggregation and that of blood coagulation have been found to be increased in the morning whereas fibrinolytic activity is lower at this time of the day. The facts suggest a chronotherapeutic approach in thromboembolic disorders.
Animals↗
[Current indications for inferior vena cava interruption].
Clinical indications of vena cava interruption are reviewed. During the last few years pulmonary embolism frequency remained high and many new percutaneous vena caval filters became available. These facts probably explain the increasing use of these filters reaching about 10,000 filters each year in France. Existing data show that: embolic risk with antithrombotic agents is less than 5%, probably not far greater than embolic risk with cava filters (about 2%); complications encountered with the filters are caval thrombosis in 8%, and more or less than 4% other major complications; there is no controlled study comparing antithrombotic treatment associated with caval filters to antithrombotic treatment alone; there is no controlled study comparing new cava filters among them or to the Greenfield filter; economical implications of caval filters are mostly unknown. The only admitted indications of vena cava interruption, in case of proximal venous thrombosis, are contraindications to anticoagulation. In other situations no data allow to recommend a cava filter; indication will be discussed on a case by case basis. Prospective controlled studies are greatly encouraged.
Heparin↗
[Lung pseudotumor caused by Corynebacterium equi in an AIDS patient].
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Good clinical practices in phase I studies.
In France, official guidelines for good clinical practices in clinical trials were issued in 1987. In December 1988, a law was passed that fixed the requirements for carrying out experiments in healthy subjects. It will be completed by official guidelines for the structures in which experiments on healthy subjects (and patients as well, when the investigation would not benefit the health of the patients) may be conducted. Hence a battery of recent legal instructions precisely state what good clinical practices are in the setting of phase I studies. Of particular importance are: subject recruitment and selection methods and procedures; specific competence of the investigator, in particular to interpret the pre-trial data; necessary and sufficient facilities to guarantee the subjects' safety; careful quality control to check all laboratory procedures; necessity of written standard operating procedures.
Drug Evaluation↗
Circadian changes in the pharmacokinetics of oral ketoprofen.
Several investigations which have taken treatment time into account have shown that the pharmacokinetic parameters, the therapeutic efficacy and even the toxicity of a large number of products may vary according to the administration schedule. The present study was carried out in order to evaluate any circadian changes in pharmacokinetic parameters of ketoprofen, a new non-steroidal anti-inflammatory drug (NSAID). This randomised crossover study consisted of a single oral dose of ketoprofen 100mg administered to 8 healthy male volunteers, mean age 27.2 years, at 07.00 hours, 13.00 hours, 19.00 hours or 01.00 hours in 4 study periods during the first 3 months of the year. The order of administration was randomised, with each subject acting as his own control. A total of 14 blood and 4 urine samples were taken over a 12-hour period. The peak plasma concentration was twice as high after drug administration at 07.00 hours (13.4 +/- 1 mg/L) than after other administration times (13.00 hours: 6.9 +/- 1; 19.00 hours: 7.2 +/- 0.7; 01.00 hours: 6.3 +/- 0.5 mg/L) [p less than 0.001]. The time to reach peak concentration was much longer after drug administration at 01.00 hours (135 +/- 16.7 min) than at 07.00 (73.1 +/- 14.1 min), 13.00 (75 +/- 16.5 min) or 19.00 hours (82.5 +/- 12.7 min) [p less than 0.05]. The lag time was significantly longer at 01.00 hours than at 13.00 hours (p less than 0.01). The absorption rate constant after treatment at 01.00 hours was less than at the other times of administration (p less than 0.05). The bodyweight-corrected area under the curve (AUC0-12) was greater after 07.00 hours than after 13.00 (p less than 0.01) or 19.00 hours (p less than 0.05) and greater after 01.00 hours than after 13.00 hours (p less than 0.05). The elimination half-life was significantly longer after administration at 01.00 hours than after 19.00 hours (p less than 0.05), while the total clearance was lowest at 07.00 hours. Cosinor analysis demonstrated statistically significant circadian rhythms for all pharmacokinetic parameters described above. The amount of ketoprofen eliminated in the urine was delayed, and was significantly greater after the administration at 01.00 hours than 07.00 hours or 19.00 hours (p less than 0.01). The relationship between absorption, diffusion and/or elimination mechanisms of the drug are discussed.
Administration, Oral↗
[Biological rhythm and thromboembolic disease. Physiological, epidemiological and pharmacological aspects].
Arterial and venous thromboembolic disorders are the leading cause of death in most of the advanced nations. The study of physiologic, epidemiologic and pharmacologic relationships of these disorders to biological rhythms, may lead to a better understanding and perhaps a better treatment. Chronophysiologic studies have shown that hemostatic variables follow circadian rhythms. The level of platelets aggregation and of blood coagulation has been found to be increased in the morning and decreased at night, whereas fibrinolytic activity is lower in the morning than in the evening. Chronoepidemiologic studies demonstrated a morning peak for arterial thromboembolic disorders and an evening peak for cerebral bleedings. These facts might partially be explained by circadian variations in hemostasis and suggest a chronotherapeutic approach in thromboembolic disorders. Unfractionated heparin, because of its antithrombotic effect, is one of the major drugs used to treat this disease. However, with such a treatment venous thrombosis recurs or bleeding complications occur yet in about 30% of patients. Chronopharmacologic studies indicate that anticoagulant effect of heparin is minimum in the morning and maximum at night, following the physiologic circadian variation of blood coagulation. Such results suggest that the heparin doses should be modulated as a function of administration times in order to increase its effectiveness and to minimize both bleeding risk and thrombosis. Further studies are needed to evaluate such a proposal.
Biological Clocks↗
Hepatitis induced by isoxicam.
Explore the source record for details and available documents.
Anti-Inflammatory Agents↗
Nycthemeral variations of 99Tcm-labelled heparin pharmacokinetic parameters.
Six healthy volunteers (5 males and one female) received four i.v. boluses of 160 U.I. of 99Tcm-heparin at 8.00, 14.00, 20.00 and 02.00 hours at seven-day intervals. Nine blood samples were taken covering a period of 2 h after administration. Simultaneously urine was collected and diuresis was noted. Plasma and urinary radioactivity were measured and standard pharmacokinetic parameters were calculated. Nycthemeral variations of these kinetic parameters were detected by means of distribution-free tests. Circadian rhythms (period = 24 h) were analysed by means of the cosinor method and the Gauss-Marquardt method. The mean raw value of the following parameters: apparent volume of distribution, plasmatic clearance and extra-renal metabolic clearance, increased significantly between 8.00 and 14.00 (p less than 0.01) and decreased between 14.00 and 20.00 (p less than 0.05). A circadian rhythm was found for the plasmatic clearance only (p less than 0.04). On the other hand the elimination half-lives and the renal clearance were unaffected by the time of the injections. These results obtained for low doses of 99Tcm-heparin suggest a circadian rhythm of the bio-availability of heparin in man. This fact should be taken into account for the use of 99Tcm-heparin in the diagnosis of deep-vein thrombosis and for the safe adjustment of the heparin dosages in the treatment of severe thromboembolism.
Circadian Rhythm↗
[Self-medication in rheumatologic consultation. Apropos of a study on 895 patients].
A study was undertaken to evaluate the use of self-administered medication in 895 patients with rheumatologic disorders by all of the 18 rheumatologists practicing in one region (the southern portion of the Loire Department and all of the Haute-Loire Department) over a six-day period. It was noted that 445 out of 895 patients (49.72 percent) reported taking one or several medications other than those prescribed during the previous 3 month period before their office visit. Self-administered medications were taken at least weekly in 53.5 percent of cases and at least monthly in 83,7 percent. Most often one or two medications were involved (60.9 and 25.6 percent respectively). Age, profession, the presence or absence of psychiatric disturbances, the duration of the doctor-patient relationship, as well as the patient's specific rheumatologic problem seemed to be influencing factors. Aspirin or other analgesics comprised 53.1 percent of the medication taken, whereas other non-steroidal antiinflammatory agents comprised only 2.3 percent. No steroids were self-administered. There are multiple potential side effects with self-administered drugs: therapy can be poorly suited for the illness in question, it may delay diagnosis and the beginning of effective therapy, there can be increased iatrogenic risk due to inadequate therapy, and unnecessary expense. Drugs used as self-administered medications originate most often from previous medical prescriptions which may or may not have been prescribed for the patient's same medical problem (34.4 percent), and most medication used was bought without needing a prescription (52.4 percent). Prevention, therefore, requires that potential consumers of self-administered drugs be educated concerning these problems, as well as health professionals, the pharmaceutical industry, and concerned government agencies.
Adolescent↗
[Nycthemeral change in the anticoagulant effect of heparin given at a constant rate by the intravenous route].
Six subjects with venous thromboembolism volunteered for this prospective study. Heparin was administrated intravenously at a constant rate with an infusion pump. The activated partial thromboplastin time (A.P.T.T.) and thrombin time (T.T.) were measured every 4 hrs. for 48 hrs. These coagulation tests exhibited a nycthemeral variation with a large amplitude which was reproducible from one day to the next and statistically validated by the cosinor method (p less than 0.001). All patients had a nocturnal peak of A.P.T.T. and T.T. on both days. In four patients this peak for A.P.T.T. exceeded the upper desired limit.
Aged↗
[Chronokinetics of ketoprofen administered orally and by continuous venous infusion].
The aim of the study was to evaluate a possible chronokinetic phenomenon of ketoprofen administered orally and by continuous intravenous infusion. In the first part of the study, ketoprofen was administered orally to 8 healthy male volunteers aged between 25 and 45 years, at a dose of 2 X 50 mg at 7:00 a.m. (time I), 1:00 p.m. (time II), 7:00 p.m. (time III) and 1:00 a.m. (time IV), on the same day of the week at an interval of 2 weeks, during the first three months of the year. The order of administration was randomised, each subject acted as his own control and received ketoprofen at the four times mentioned above. A total of 14 venous blood samples were taken over 12 hours. The results indicate that the maximal serum concentration (Cmax) was significantly higher at time I (13.4 +/- 14.1) than at times II, III and IV (6.9 +/- 1.1, 7.2 +/- 0.7, 6.4 +/- 0.5 mg/l) (p less than 0.01). The time required to reach this concentration (Tmax) was significantly longer for time IV (135.0 +/- 16,8) than for times I, II and III (73,1 +/- 14.1, 75,0 +/- 16.6; 82.5 +/- 12.7 minutes) (p less than 0.05). The excretion half-life (t 1/2B) was significantly longer for time IV (4.3 +/- 0.6) than for times II and III (2.8 +/- 0.5, 2.5 +/- 0.2 hours) (p less than 0.05). Statistically significant differences were also observed in the area under the curve measured at midday (AUC 12) and in the total clearance (CIT) for the various sample times.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
[Macroglossia in apparently primary amyloidosis].
The authors report a case of apparently primary amyloidosis in which macroglossia was the clinical presentation, confirmed by lingual biopsy. They take advantage of this case to review the therapeutic possibilities, though stating that from a stomatological standpoint there is virtually nothing available.
Aged↗
[Non-steroidal anti-inflammatory agents. Evaluation criteria in discal sciatic neuralgia].
Few controlled trials have been carried out with non-steroidal antiinflammatory drugs in this indication, mainly as a result of methodological difficulties. A prerequisite for correct evaluation is compliance with certain fundamental principles. The study must be controlled (i.e. comparative, prospective randomized, double-blind, with data quality control and statistical analysis). The sample size must be consistent with the objectives (at least 40 patients per group). The selection criteria must be well specified and the comparability of baseline data assessed. The most appropriate study design for assessing clinical efficacy is to compare two parallel groups of out patients treated during five to fifteen days. The main criterion of efficacy should be based on the judgments of both patients and physician. Time course of pain, improvement in the patient's functional capacity, improvement in physical findings (Schober, Lasègue), dosage of concomitant analgesic treatments when these are allowed, and evaluation at three and six months can also be used as efficacy criteria. Assessment of clinical and biological tolerance is mandatory. Considering the frequent use of non-steroidal antiinflammatory drugs in treating sciatica, there is a strong need for rigorous investigations.
Anti-Inflammatory Agents↗
[Influence of tobacco on the serum levels and pharmacokinetics of phenylbutazone and oxyphenbutazone].
The serum levels of a number of drugs are reduced by smoking. The authors wanted to see whether this phenomenon occurred with phenylbutazone. With this objective, they compared the changes in serum levels of phenylbutazone and oxyphenbutazone, the hydroxylated metabolite of phenylbutazone, during ten days of administration, in 9 smokers and in 6 non-smokers. Blood samples were taken every day at 8:00 a.m. and the PB and OPB were assayed by high performance liquid chromatography. The comparison of the mean serum levels of PB in smokers and non-smokers revealed a statistically significant reduction (p less than or equal to 0.05) of this level in the smoker, between D5 and D10. Comparison of the mean serum levels of OPB in smokers and non-smokers revealed a statistically significant reduction of this level in the smoker, but only on days 9 and 10. When we compare these results with those reported in the literature for other drugs, it would appear that tobacco smoke accelerates the metabolism of phenylbutazone and oxyphenbutazone by a mechanism of enzyme induction. It is proposed that the therapeutic activity of phenylbutazone is reduced in the smoker, but this has not been confirmed by a reliable clinical evaluation in this initial study.
Adult↗
[Value of anti hemolysin and anti-gammahemolysin assays for the diagnosis of staphylococcal infections, particularly of osteoarthritis (author's transl)].
The authors report the results of more than twelve years' personal research on the value of anti-alphahemolysin (AASTL) and antigammahemolysin (AGSTL) assays for the diagnosis of staphylococcal infections, and particularly of osteoarthritis. Among 574 controls, AASTL levels exceeded 2 IU in only 14 subjects (11 of these, levels were between 2 and 3 IU). Levels less than, or equal to, 2 IU were therefore considered normal. This is consistent with previously published data. In 144 staphylococcal infections, confirmed by bacteriology, an increase in AASTL was found in 95 of all cases (65.9%) and in 54 of the 76 osteoarthritis' (71%). Similarly, AGSTL titres, which were under 1/160 (upper normal limit) in 138 controls, were increased in 35 patients with unequivocal staphylococcal infections (61.4%), and in 25 of 36 patients with osteoarthritis (69.4%). These results show that AASTL assay is reliable and often abnormal. However, assay of both hemolysins yields even better results. This dual assay was performed in 57 patients with staphylococcal infection. One hemolysin at least was increased in 47 patients (82.4%). This represents additional positivity in 15.7% of patients when compared to AASTL assay alone, and in 21% when compared to AGSTL assay alone. The high level of positive results with dual assay is even more striking when only staphylococcal osteoarthritis is considered: one or both hemolysins were increased in 91.1% of these patients (31/34).
Antibodies, Bacterial↗