P. Nony | Université Claude Bernard Lyon 1 (original) (raw)
Papers by P. Nony
Archives des maladies du coeur et des vaisseaux, 1991
The authors report two cases of anomalous origin of the left coronary artery from the pulmonary a... more The authors report two cases of anomalous origin of the left coronary artery from the pulmonary artery in the adult. The two patients were pauci-symptomatic and were successfully operated, the one by reimplantation of the left coronary artery in the aorta and the other by an internal mammary artery left anterior descending artery bypass. Resting and stress myocardial scintigraphy and radionuclide ventriculography were performed before and after surgery in both cases. An analysis of segmental wall motion was possible in one patient. Before surgery, there was hypo-fixation of the tracer during the stress test and an alteration of left ventricular function. Postoperative isotopic investigations confirmed the efficacy of surgery the absence of regional ischemia and the normalisation of the ventricular contraction. These results argue in favour of a surgical reconstruction of a two coronary system, given the spontaneous risk of sudden death in this condition.
Annales de cardiologie et d'angeiologie, 1996
In order to evaluate the place of dobutamine echocardiography in everyday practice, this test and... more In order to evaluate the place of dobutamine echocardiography in everyday practice, this test and a stress ECG were performed in 34 patients referred for diagnostic or assessment coronary angiography. Dobutamine, administered in 3-minute stages from 5 to 30 micrograms/kg/min, was well tolerated. The anti-ischaemic treatment was continued in 26 patients before dobutamine echocardiography and in 15 patients before the stress ECG. The electrocardiographic, echocardiographic and angiographic documents were each analysed by 2 independent observers. Dobutamine echocardiography was considered to be positive in the presence of the development of a new abnormality of segmental kinetics or when abnormality of segmental kinetics was identified outside of the territory of infarction. With reference to coronary angiography, the sensitivity of stress ECG and dobutamine echocardiography was 46% and 42%, respectively, and the specificity was 75% and 88%, respectively; the sensitivity of each test w...
Therapie, 1999
In chronic illness, when death or a non-fatal event can occur at any time, the current efficacy i... more In chronic illness, when death or a non-fatal event can occur at any time, the current efficacy indices are no longer appropriate to express the effect of the treatment on the potential therapeutic objectives. The inappropriateness is not dependent on the effect model. Clues for solutions are proposed.
Thrombosis Research
AIM The direct oral anticoagulants (DOAC) have similar half-lives, but the dosing regimen varies ... more AIM The direct oral anticoagulants (DOAC) have similar half-lives, but the dosing regimen varies between once daily (QD) or twice daily (BID). For some prescribers, the QD regimen improves compliance. Others prefer BID regimens to promote better stability of plasma concentrations, particularly in the event of missed doses. Limited level of evidence provides guidance about the best treatment strategy. The purpose of this study was to compare the treatment effect of QD vs. BID administration of DOACs in major orthopedic surgery (MOS), non-valvular atrial fibrillation (NVAF), venous thromboembolism (VTE), and acute coronary syndrome (ACS). METHODS We conducted a systematic review up to April 2020. We included phase II clinical trials comparing DOAC QD vs BID with same daily dose. We extracted data for the occurrence of major thrombosis (proximal deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke) and major hemorrhage (ISTH criteria and recommendations of the European Medicines Agency for surgical patients). Relative risks (RR) were combined using a fixed and random effects weighted meta-analysis. RESULTS Twelve randomized, controlled, phase II trials were included (10,716 patients), representing 24 dosing regimen comparisons of apixaban, darexaban, edoxaban, rivaroxaban, letaxaban, and dabigatran. There was no difference for major thrombotic event (RRBID/QD = 1.06, 95%IC 0.86-1.30) nor for major bleeding (RRBID/QD = 1.02, 95%IC 0.84-1.23) between the BID vs QD regimens, without heterogeneity (I2 = 0%). CONCLUSION Our study does not support a global difference in term of efficacy and safety of the BID and QD regimens of DOAC in MOS, NVAF, VTE and ACS.
In Silico Biology
A dynamical model of the pathophysiological behaviors of IL18 and IL10 cytokines with their recep... more A dynamical model of the pathophysiological behaviors of IL18 and IL10 cytokines with their receptors is tested against data for the case of early sepsis. The proposed approach considers the surroundings (organs and bone marrow) and the different subsystems (cells and cyctokines). The interactions between blood cells, cytokines and the surroundings are described via mass balances. Cytokines are adsorbed onto associated receptors at the cell surface. The adsorption is described by the Langmuir model and gives rise to the production of more cytokines and associated receptors inside the cell. The quantities of pro and anti-inflammatory cytokines present in the body are combined to give global information via an inflammation level function which describes the patient's state. Data for parameter estimation comes from the Sepsis 48 H database. Comparisons between patient data and simulations are presented and are in good agreement. For the IL18/IL10 cytokine pair, 5 key parameters have been found. They are linked to pro-inflammatory IL18 cytokine and show that the early sepsis is driven by components of inflammatory character.
Toxicologie Analytique et Clinique
Mathematical Modelling of Natural Phenomena, 2016
Deep venous thrombosis (DVT) is characterized by formation of blood clot within a deep vein. The ... more Deep venous thrombosis (DVT) is characterized by formation of blood clot within a deep vein. The resulting thrombus can partially or completely block blood circulation. It can also detach and migrate with the flow resulting in pulmonary embolism. Anticoagulant drugs such as warfarin are usually prescribed to prevent recurrent thrombosis. The action of warfarin is monitored using a blood test for the International Normalized Ratio (INR) which is based on prothrombin time measurement. A high INR indicates a predisposition of the patient to bleeding, while a low INR shows that the warfarin dose is insufficient to prevent thromboembolic events. The therapeutic target of INR varies from case to case depending on clinical indications. It tends to be in the range 2.0 – 3.0 in most conditions. In this work we develop a model describing blood clotting during warfarin treatment. The action of warfarin is introduced by a Pharmacokinetics-Pharmacodynamics (PK-PD) sub-model. It describes the inhibition of synthesis of the vitamin K dependent factors by warfarin in the liver. We generate a population of patients with individual characteristics and assess their response to warfarin treatment by comparing the simulated INR and the corresponding developed clot height. Using this approach, we determine the underlying causes behind thrombosis and bleeding persistence even for an INR in the normal range. Thus, we suggest a novel methodology to predict the targeted INR depending on individual patient characteristics.
International Journal for Numerical Methods in Biomedical Engineering, 2017
Vessel occlusion is a perturbation of blood flow inside a blood vessel because of the fibrin clot... more Vessel occlusion is a perturbation of blood flow inside a blood vessel because of the fibrin clot formation. As a result, blood circulation in the vessel can be slowed down or even stopped provoking the risk of cardiovascular events. In order to explore this phenomenon, we suggest a mathematical model of blood clotting. We describe the concentrations of blood factors with reaction-diffusion system of equations, blood flow is modelled with the Navier-Stokes equations with clot considered as a porous medium. We identify the conditions of partial or complete occlusion in a small vessel depending on various physical and physiological parameters. The obtained results are then compared with the analytical conditions on the arterial occlusion for the simplified mathematical model. We observe different regimes of vessel occlusion depending on the model parameters both for numerical simulations and in theoretical study.
Annales de cardiologie et d'angéiologie, 1996
In order to evaluate the place of dobutamine echocardiography in everyday practice, this test and... more In order to evaluate the place of dobutamine echocardiography in everyday practice, this test and a stress ECG were performed in 34 patients referred for diagnostic or assessment coronary angiography. Dobutamine, administered in 3-minute stages from 5 to 30 micrograms/kg/min, was well tolerated. The anti-ischaemic treatment was continued in 26 patients before dobutamine echocardiography and in 15 patients before the stress ECG. The electrocardiographic, echocardiographic and angiographic documents were each analysed by 2 independent observers. Dobutamine echocardiography was considered to be positive in the presence of the development of a new abnormality of segmental kinetics or when abnormality of segmental kinetics was identified outside of the territory of infarction. With reference to coronary angiography, the sensitivity of stress ECG and dobutamine echocardiography was 46% and 42%, respectively, and the specificity was 75% and 88%, respectively; the sensitivity of each test w...
Thérapie
We performed a meta-analysis on data from trials of calcium antagonist drugs in the secondary pre... more We performed a meta-analysis on data from trials of calcium antagonist drugs in the secondary prevention of myocardial infarction. Nifedipine (9,033 patients) increased total mortality non significantly by 12% at the end of follow-up, and by 62% (p = 0.02) before 21 days, with no significant change in the risk of reinfarction. Diltiazem or verapamil did not change total mortality significantly; each of them decreased the risk of reinfarction not significantly (p = 0.06) by approximately 20%. Treatment by either diltiazem or verapamil (8,356 patients) decreased the risk of reinfarction by 21% (p = 0.009). No benefit has been demonstrated with nifedipine in the secondary prevention of myocardial infarction. Verapamil or diltiazem may be an alternative to beta-blockers when these lasts drugs are contra-indicated, although one cannot reasonably expect from the first two drugs a decrease in mortality.
Cardiology, 1996
The negative conduction effect of quinidine on each of the successive phases of the ventricular d... more The negative conduction effect of quinidine on each of the successive phases of the ventricular depolarization was investigated using an original noninvasive method: the spatial velocity electrocardiogram of the QRS complex (SVECG-QRS). We performed a randomized placebo-controlled trial in 10 healthy subjects with a single oral dose of quinidine (330 mg) or placebo. Electrocardiographic acquisition and processing (220 recordings for the complete trial) were performed using the Lyon vectorcardiographic program. For each SVECG-QRS curve, the position of seven specific points from A (onset of QRS) to G (end of QRS) were determined precisely. The six successive time intervals between these points (AB-FG) and five velocity values (B-F) were then calculated. The QRS complex was longer under quinidine than placebo (102.4 +/- 1.6 vs. 100.3 +/- 1.5 ms). The difference was at the periphery of statistical significance (p = 0.05), and this lack of statistical difference may be mainly due to the low serum levels of quinidine obtained at the peak of the concentration (1.46 +/- 0.4 mg/1). All six QRS time intervals were longer under quinidine, but only the BC interval was significantly different (9.3 +/- 1.1 vs. 18.8 +/- 1.1 ms; p < 0.05) suggesting a more pronounced negative conduction effect at the onset of ventricular depolarization. No significant modifications were observed for the velocity values. We conclude that (1) the negative conduction effect of quinidine is heterogeneous, but a further study with a higher dose of quinidine (concentration-dependent effect) is required to confirm this hypothesis and (2) the spatial velocity electrocardiogram of the QRS complex allows a detailed analysis of the ventricular conduction phases. The results of the measurement were found to be reproducible. This noninvasive tool could be used in clinical practice to assess effects of antiarrhythmic drugs on successive ventricular depolarization phases.
Controlled clinical …, 1995
Protocols for dose ranging trials in healthy volunteers or patients can be described by the combi... more Protocols for dose ranging trials in healthy volunteers or patients can be described by the combination of an experimental design and one or more decision rules. Generally, the doses are chosen on the basis of an up-and-down method, until the maximum tolerated (affecting one or ...
Cancer Chemotherapy and Pharmacology, 1987
Three hours after i. v. administration of doxorubicin, concentrations of the drug in the myocardi... more Three hours after i. v. administration of doxorubicin, concentrations of the drug in the myocardium are much higher (about 50 times) and decrease much more slowly (drug still detected 21 days later) than those in the plasma, so that storage results from too early readministration, with possible toxic signs.
Circulation, 2001
Background-The optimal duration of oral anticoagulant therapy after a first episode of venous thr... more Background-The optimal duration of oral anticoagulant therapy after a first episode of venous thromboembolism remains controversial. Methods and Results-We performed an open-label, randomized trial comparing a short oral anticoagulant course (3 months for proximal deep vein thrombosis [P-DVT] and/or pulmonary embolism [PE]; 6 weeks for isolated calf DVT [C-DVT]) with a long course of therapy (6 months for P-DVT/PE; 12 weeks for C-DVT). The outcome events were recurrences and major, minor, or fatal bleeding complications. A total of 736 patients were enrolled. There were 23 recurrences of venous thromboembolism in the short treatment group (6.4%) and 26 in the long treatment group (7.4%); the 2 treatment regimens had an equivalent effect. For the hemorrhage end point, the difference between the short and the long treatment groups was not significant: 15.5% versus 18.4% for all events (Pϭ0.302), 1.7% versus 2.8% (Pϭ0.291) for major events, and 13.9% versus 15.3% for minor bleeding. Subgroup analysis demonstrated that the rate of recurrence was lower for C-DVT than for P-DVT or PE. Conclusions-After isolated C-DVT, 6 weeks of oral anticoagulation is sufficient. For P-DVT or PE, we demonstrated an equivalence between 3 and 6 months of anticoagulant therapy. For patients with temporary risk factors who have a low risk of recurrence, 3 months of treatment seems to be sufficient. For patients with idiopathic venous thromboembolism or permanent risk factors who have a high risk of recurrence, other trials are necessary to assess prolonged therapy beyond 6 months.
Mathematical Medicine and Biology, 2017
T lymphoblastic lymphoma (T-LBL) is a rare type of lymphoma with a good prognosis with a remissio... more T lymphoblastic lymphoma (T-LBL) is a rare type of lymphoma with a good prognosis with a remission rate of 85%. Patients can be completely cured or can relapse during or after a 2-year treatment. Relapses usually occur early after the remission of the acute phase. The median time of relapse is equal to 1 year, after the occurrence of complete remission (range 0.2-5.9 years) (Uyttebroeck et al., 2008). It can be assumed that patients may be treated longer than necessary with undue toxicity. The aim of our model was to investigate whether the duration of the maintenance therapy could be reduced without increasing the risk of relapses and to determine the minimum treatment duration that could be tested in a future clinical trial.
La Revue de Médecine Interne, 1999
Clinical Cardiology
Anomalous origin of left coronary vessel from the pulmonary artery is an almost universally fatal... more Anomalous origin of left coronary vessel from the pulmonary artery is an almost universally fatal form of congenital heart disease unless appropriate corrective surgery is performed at an early age. A case was diagnosed in a symptomatic 44-year-old man who presented an impairment of systolic left ventricular function. The abnormality was successfully treated with ligation of the left coronary artery combined with left internal mammary artery anastomosis. Left ventricular function improved dramatically six months after surgery, both at rest and during exercise. Such an evolution suggests that surgery may be indicated not only in infants but also in adults with this congenital heart abnormality.
Archives des maladies du coeur et des vaisseaux, 1991
The authors report two cases of anomalous origin of the left coronary artery from the pulmonary a... more The authors report two cases of anomalous origin of the left coronary artery from the pulmonary artery in the adult. The two patients were pauci-symptomatic and were successfully operated, the one by reimplantation of the left coronary artery in the aorta and the other by an internal mammary artery left anterior descending artery bypass. Resting and stress myocardial scintigraphy and radionuclide ventriculography were performed before and after surgery in both cases. An analysis of segmental wall motion was possible in one patient. Before surgery, there was hypo-fixation of the tracer during the stress test and an alteration of left ventricular function. Postoperative isotopic investigations confirmed the efficacy of surgery the absence of regional ischemia and the normalisation of the ventricular contraction. These results argue in favour of a surgical reconstruction of a two coronary system, given the spontaneous risk of sudden death in this condition.
Annales de cardiologie et d'angeiologie, 1996
In order to evaluate the place of dobutamine echocardiography in everyday practice, this test and... more In order to evaluate the place of dobutamine echocardiography in everyday practice, this test and a stress ECG were performed in 34 patients referred for diagnostic or assessment coronary angiography. Dobutamine, administered in 3-minute stages from 5 to 30 micrograms/kg/min, was well tolerated. The anti-ischaemic treatment was continued in 26 patients before dobutamine echocardiography and in 15 patients before the stress ECG. The electrocardiographic, echocardiographic and angiographic documents were each analysed by 2 independent observers. Dobutamine echocardiography was considered to be positive in the presence of the development of a new abnormality of segmental kinetics or when abnormality of segmental kinetics was identified outside of the territory of infarction. With reference to coronary angiography, the sensitivity of stress ECG and dobutamine echocardiography was 46% and 42%, respectively, and the specificity was 75% and 88%, respectively; the sensitivity of each test w...
Therapie, 1999
In chronic illness, when death or a non-fatal event can occur at any time, the current efficacy i... more In chronic illness, when death or a non-fatal event can occur at any time, the current efficacy indices are no longer appropriate to express the effect of the treatment on the potential therapeutic objectives. The inappropriateness is not dependent on the effect model. Clues for solutions are proposed.
Thrombosis Research
AIM The direct oral anticoagulants (DOAC) have similar half-lives, but the dosing regimen varies ... more AIM The direct oral anticoagulants (DOAC) have similar half-lives, but the dosing regimen varies between once daily (QD) or twice daily (BID). For some prescribers, the QD regimen improves compliance. Others prefer BID regimens to promote better stability of plasma concentrations, particularly in the event of missed doses. Limited level of evidence provides guidance about the best treatment strategy. The purpose of this study was to compare the treatment effect of QD vs. BID administration of DOACs in major orthopedic surgery (MOS), non-valvular atrial fibrillation (NVAF), venous thromboembolism (VTE), and acute coronary syndrome (ACS). METHODS We conducted a systematic review up to April 2020. We included phase II clinical trials comparing DOAC QD vs BID with same daily dose. We extracted data for the occurrence of major thrombosis (proximal deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke) and major hemorrhage (ISTH criteria and recommendations of the European Medicines Agency for surgical patients). Relative risks (RR) were combined using a fixed and random effects weighted meta-analysis. RESULTS Twelve randomized, controlled, phase II trials were included (10,716 patients), representing 24 dosing regimen comparisons of apixaban, darexaban, edoxaban, rivaroxaban, letaxaban, and dabigatran. There was no difference for major thrombotic event (RRBID/QD = 1.06, 95%IC 0.86-1.30) nor for major bleeding (RRBID/QD = 1.02, 95%IC 0.84-1.23) between the BID vs QD regimens, without heterogeneity (I2 = 0%). CONCLUSION Our study does not support a global difference in term of efficacy and safety of the BID and QD regimens of DOAC in MOS, NVAF, VTE and ACS.
In Silico Biology
A dynamical model of the pathophysiological behaviors of IL18 and IL10 cytokines with their recep... more A dynamical model of the pathophysiological behaviors of IL18 and IL10 cytokines with their receptors is tested against data for the case of early sepsis. The proposed approach considers the surroundings (organs and bone marrow) and the different subsystems (cells and cyctokines). The interactions between blood cells, cytokines and the surroundings are described via mass balances. Cytokines are adsorbed onto associated receptors at the cell surface. The adsorption is described by the Langmuir model and gives rise to the production of more cytokines and associated receptors inside the cell. The quantities of pro and anti-inflammatory cytokines present in the body are combined to give global information via an inflammation level function which describes the patient's state. Data for parameter estimation comes from the Sepsis 48 H database. Comparisons between patient data and simulations are presented and are in good agreement. For the IL18/IL10 cytokine pair, 5 key parameters have been found. They are linked to pro-inflammatory IL18 cytokine and show that the early sepsis is driven by components of inflammatory character.
Toxicologie Analytique et Clinique
Mathematical Modelling of Natural Phenomena, 2016
Deep venous thrombosis (DVT) is characterized by formation of blood clot within a deep vein. The ... more Deep venous thrombosis (DVT) is characterized by formation of blood clot within a deep vein. The resulting thrombus can partially or completely block blood circulation. It can also detach and migrate with the flow resulting in pulmonary embolism. Anticoagulant drugs such as warfarin are usually prescribed to prevent recurrent thrombosis. The action of warfarin is monitored using a blood test for the International Normalized Ratio (INR) which is based on prothrombin time measurement. A high INR indicates a predisposition of the patient to bleeding, while a low INR shows that the warfarin dose is insufficient to prevent thromboembolic events. The therapeutic target of INR varies from case to case depending on clinical indications. It tends to be in the range 2.0 – 3.0 in most conditions. In this work we develop a model describing blood clotting during warfarin treatment. The action of warfarin is introduced by a Pharmacokinetics-Pharmacodynamics (PK-PD) sub-model. It describes the inhibition of synthesis of the vitamin K dependent factors by warfarin in the liver. We generate a population of patients with individual characteristics and assess their response to warfarin treatment by comparing the simulated INR and the corresponding developed clot height. Using this approach, we determine the underlying causes behind thrombosis and bleeding persistence even for an INR in the normal range. Thus, we suggest a novel methodology to predict the targeted INR depending on individual patient characteristics.
International Journal for Numerical Methods in Biomedical Engineering, 2017
Vessel occlusion is a perturbation of blood flow inside a blood vessel because of the fibrin clot... more Vessel occlusion is a perturbation of blood flow inside a blood vessel because of the fibrin clot formation. As a result, blood circulation in the vessel can be slowed down or even stopped provoking the risk of cardiovascular events. In order to explore this phenomenon, we suggest a mathematical model of blood clotting. We describe the concentrations of blood factors with reaction-diffusion system of equations, blood flow is modelled with the Navier-Stokes equations with clot considered as a porous medium. We identify the conditions of partial or complete occlusion in a small vessel depending on various physical and physiological parameters. The obtained results are then compared with the analytical conditions on the arterial occlusion for the simplified mathematical model. We observe different regimes of vessel occlusion depending on the model parameters both for numerical simulations and in theoretical study.
Annales de cardiologie et d'angéiologie, 1996
In order to evaluate the place of dobutamine echocardiography in everyday practice, this test and... more In order to evaluate the place of dobutamine echocardiography in everyday practice, this test and a stress ECG were performed in 34 patients referred for diagnostic or assessment coronary angiography. Dobutamine, administered in 3-minute stages from 5 to 30 micrograms/kg/min, was well tolerated. The anti-ischaemic treatment was continued in 26 patients before dobutamine echocardiography and in 15 patients before the stress ECG. The electrocardiographic, echocardiographic and angiographic documents were each analysed by 2 independent observers. Dobutamine echocardiography was considered to be positive in the presence of the development of a new abnormality of segmental kinetics or when abnormality of segmental kinetics was identified outside of the territory of infarction. With reference to coronary angiography, the sensitivity of stress ECG and dobutamine echocardiography was 46% and 42%, respectively, and the specificity was 75% and 88%, respectively; the sensitivity of each test w...
Thérapie
We performed a meta-analysis on data from trials of calcium antagonist drugs in the secondary pre... more We performed a meta-analysis on data from trials of calcium antagonist drugs in the secondary prevention of myocardial infarction. Nifedipine (9,033 patients) increased total mortality non significantly by 12% at the end of follow-up, and by 62% (p = 0.02) before 21 days, with no significant change in the risk of reinfarction. Diltiazem or verapamil did not change total mortality significantly; each of them decreased the risk of reinfarction not significantly (p = 0.06) by approximately 20%. Treatment by either diltiazem or verapamil (8,356 patients) decreased the risk of reinfarction by 21% (p = 0.009). No benefit has been demonstrated with nifedipine in the secondary prevention of myocardial infarction. Verapamil or diltiazem may be an alternative to beta-blockers when these lasts drugs are contra-indicated, although one cannot reasonably expect from the first two drugs a decrease in mortality.
Cardiology, 1996
The negative conduction effect of quinidine on each of the successive phases of the ventricular d... more The negative conduction effect of quinidine on each of the successive phases of the ventricular depolarization was investigated using an original noninvasive method: the spatial velocity electrocardiogram of the QRS complex (SVECG-QRS). We performed a randomized placebo-controlled trial in 10 healthy subjects with a single oral dose of quinidine (330 mg) or placebo. Electrocardiographic acquisition and processing (220 recordings for the complete trial) were performed using the Lyon vectorcardiographic program. For each SVECG-QRS curve, the position of seven specific points from A (onset of QRS) to G (end of QRS) were determined precisely. The six successive time intervals between these points (AB-FG) and five velocity values (B-F) were then calculated. The QRS complex was longer under quinidine than placebo (102.4 +/- 1.6 vs. 100.3 +/- 1.5 ms). The difference was at the periphery of statistical significance (p = 0.05), and this lack of statistical difference may be mainly due to the low serum levels of quinidine obtained at the peak of the concentration (1.46 +/- 0.4 mg/1). All six QRS time intervals were longer under quinidine, but only the BC interval was significantly different (9.3 +/- 1.1 vs. 18.8 +/- 1.1 ms; p < 0.05) suggesting a more pronounced negative conduction effect at the onset of ventricular depolarization. No significant modifications were observed for the velocity values. We conclude that (1) the negative conduction effect of quinidine is heterogeneous, but a further study with a higher dose of quinidine (concentration-dependent effect) is required to confirm this hypothesis and (2) the spatial velocity electrocardiogram of the QRS complex allows a detailed analysis of the ventricular conduction phases. The results of the measurement were found to be reproducible. This noninvasive tool could be used in clinical practice to assess effects of antiarrhythmic drugs on successive ventricular depolarization phases.
Controlled clinical …, 1995
Protocols for dose ranging trials in healthy volunteers or patients can be described by the combi... more Protocols for dose ranging trials in healthy volunteers or patients can be described by the combination of an experimental design and one or more decision rules. Generally, the doses are chosen on the basis of an up-and-down method, until the maximum tolerated (affecting one or ...
Cancer Chemotherapy and Pharmacology, 1987
Three hours after i. v. administration of doxorubicin, concentrations of the drug in the myocardi... more Three hours after i. v. administration of doxorubicin, concentrations of the drug in the myocardium are much higher (about 50 times) and decrease much more slowly (drug still detected 21 days later) than those in the plasma, so that storage results from too early readministration, with possible toxic signs.
Circulation, 2001
Background-The optimal duration of oral anticoagulant therapy after a first episode of venous thr... more Background-The optimal duration of oral anticoagulant therapy after a first episode of venous thromboembolism remains controversial. Methods and Results-We performed an open-label, randomized trial comparing a short oral anticoagulant course (3 months for proximal deep vein thrombosis [P-DVT] and/or pulmonary embolism [PE]; 6 weeks for isolated calf DVT [C-DVT]) with a long course of therapy (6 months for P-DVT/PE; 12 weeks for C-DVT). The outcome events were recurrences and major, minor, or fatal bleeding complications. A total of 736 patients were enrolled. There were 23 recurrences of venous thromboembolism in the short treatment group (6.4%) and 26 in the long treatment group (7.4%); the 2 treatment regimens had an equivalent effect. For the hemorrhage end point, the difference between the short and the long treatment groups was not significant: 15.5% versus 18.4% for all events (Pϭ0.302), 1.7% versus 2.8% (Pϭ0.291) for major events, and 13.9% versus 15.3% for minor bleeding. Subgroup analysis demonstrated that the rate of recurrence was lower for C-DVT than for P-DVT or PE. Conclusions-After isolated C-DVT, 6 weeks of oral anticoagulation is sufficient. For P-DVT or PE, we demonstrated an equivalence between 3 and 6 months of anticoagulant therapy. For patients with temporary risk factors who have a low risk of recurrence, 3 months of treatment seems to be sufficient. For patients with idiopathic venous thromboembolism or permanent risk factors who have a high risk of recurrence, other trials are necessary to assess prolonged therapy beyond 6 months.
Mathematical Medicine and Biology, 2017
T lymphoblastic lymphoma (T-LBL) is a rare type of lymphoma with a good prognosis with a remissio... more T lymphoblastic lymphoma (T-LBL) is a rare type of lymphoma with a good prognosis with a remission rate of 85%. Patients can be completely cured or can relapse during or after a 2-year treatment. Relapses usually occur early after the remission of the acute phase. The median time of relapse is equal to 1 year, after the occurrence of complete remission (range 0.2-5.9 years) (Uyttebroeck et al., 2008). It can be assumed that patients may be treated longer than necessary with undue toxicity. The aim of our model was to investigate whether the duration of the maintenance therapy could be reduced without increasing the risk of relapses and to determine the minimum treatment duration that could be tested in a future clinical trial.
La Revue de Médecine Interne, 1999
Clinical Cardiology
Anomalous origin of left coronary vessel from the pulmonary artery is an almost universally fatal... more Anomalous origin of left coronary vessel from the pulmonary artery is an almost universally fatal form of congenital heart disease unless appropriate corrective surgery is performed at an early age. A case was diagnosed in a symptomatic 44-year-old man who presented an impairment of systolic left ventricular function. The abnormality was successfully treated with ligation of the left coronary artery combined with left internal mammary artery anastomosis. Left ventricular function improved dramatically six months after surgery, both at rest and during exercise. Such an evolution suggests that surgery may be indicated not only in infants but also in adults with this congenital heart abnormality.