Michel Andréjak - Academia.edu (original) (raw)
Papers by Michel Andréjak
Circulation, 2009
Background-Chronic renal failure (CRF) is associated with cardiac dysfunction and increased aorti... more Background-Chronic renal failure (CRF) is associated with cardiac dysfunction and increased aortic stiffness. The mechanisms involved are not clearly understood. We examined changes over time in cardiac and aortic function in a murine CRF model. Methods and Results-Eight-week-old mice were randomly assigned to 1 of 4 groups: wild-type non-CRF, wild-type CRF, apolipoprotein E knockout non-CRF, and apolipoprotein E knockout CRF. Echocardiography was performed and blood samples were taken at baseline and after 6 and 10 weeks of CRF. Vascular reactivity and adhesion molecule expression were studied after 6 and 10 weeks of CRF. Left ventricular hypertrophy, altered left ventricular relaxation, and increased aortic stiffness were observed after 6 weeks of CRF and persisted after 10 weeks. The 4 groups of mice did not significantly differ in terms of arterial blood pressure and aortic structure. The degree of vascular calcification and serum total cholesterol concentration were higher in the CRF groups than in the non-CRF groups. These changes, however, could not explain the cardiac and vascular differences seen in the 2 CRF groups. In contrast, alterations in vascular reactivity, the upregulation of adhesion molecule expression, and CRF status were significantly associated with these changes. Conclusions-In a mouse model of CRF, left ventricular hypertrophy, cardiac diastolic dysfunction, and increased aortic stiffness were not related to structural changes in the aorta (including aortic calcification) or high serum cholesterol levels. However, cardiac and aortic abnormalities were associated with the extent of subendothelial dysfunction and the severity of CRF. (Circulation. 2009;119:306-313.)
British journal of clinical pharmacology, Jan 2, 2015
Voriconazole (VRC) is mainly metabolized by CYP2C19 and CYP3A4 and exhibits a wide inter- and int... more Voriconazole (VRC) is mainly metabolized by CYP2C19 and CYP3A4 and exhibits a wide inter- and intra-individual variability requiring therapeutic drug monitoring (TDM). We present a case of VRC therapy failure in a patient carrying a CYP2C19*17/*17 genotype. A 26-year-old Caucasian woman treated for an acute leukemia developed a neutropenic fever associated to a respiratory distress. Seventeen days after the introduction of a standard VRC antifungal treatment, she suffered from cough and hemoptysis, detection of fungal blood markers remained positive and chest high-resolution CT scan revealed newer lesions in lungs, suggesting a refractory aspergillosis. After a 2-hour intravenous infusion of 400mg dose, VRC concentrations were 3.48, 1.10, 0.22 and 0.17 mg/L at 2, 4, 8 and 12 hours respectively. Area under the concentration time curve from zero to infinity, clearance and terminal half-life were estimated at 11.1 h.mL/min, 35.9 L/h and 2.3 h respectively. The concentration ratio of th...
Thérapie
Veralipride is a substituted benzamide which is used for the treatment of menopausal hot flushes.... more Veralipride is a substituted benzamide which is used for the treatment of menopausal hot flushes. We report five cases with extrapyramidal disorders associated to a treatment with this drug for which the neuroleptic activity resulting from an interaction with D2 receptors is not always known by prescribers. One case consisted of acute dyskinesias and four of parkinsonian syndromes, one of these being associated with tardive dyskinesia. In these four cases, dosing recommendations were not respected.
Thérapie
Interferon alfa (INF alpha), which is used in chronic active viral hepatitis, presents some safet... more Interferon alfa (INF alpha), which is used in chronic active viral hepatitis, presents some safety problems. Side effects observed in 72 treated patients with chronic active hepatitis C are analysed in this retrospective study. Doses used were 3 or 9 M IU, three times a week, for 12 to 24 weeks. There were no contra-indications to the treatment and all patients had the factors predictive of a satisfactory therapeutic response. Apart from general debility, there were side effects in 65 of the 72 patients as follows: flu-like syndrome (n = 39), gastrointestinal (n = 29), dermatological (n = 24), haematological (n = 23), neurological (n = 20), cardiovascular (n = 6) and thyroid (n = 6) disorders. For 30 per cent of the patients, the dose was decreased (n = 6) or the treatment was withdrawn, temporarily (n = 5) or permanently (n = 10). These results are in accordance with those published and emphasize the need for clinico-biological monitoring during and after treatment. Indeed delayed ...
Thérapie
Management of tuberculosis in a hospital environment is well systematized and may include chemopr... more Management of tuberculosis in a hospital environment is well systematized and may include chemoprophylaxis, which may be hazardous when used in psychiatric impairments. We examined retrospectively adverse events occurring during a 6-month period of antituberculosis treatment. Besides patients initially treated for active pulmonary tuberculosis, 16 other patients have benefited from chemoprophylaxis with isoniazid (INH) and/or rifampicin (RFP). All these patients (mean age 53 years) had been institutionalized for several years. Fifteen of them still received a mean of 5.4 +/- 2.2 drugs including 3.3 +/- 1.4 psychotropic agents. During antituberculous treatment, 5 patients (29 per cent) presented side effects: hyperuricaemia with pyrazinamide, neutropenia, dysphagia and anorexia, dizziness and falls, diabetes and fatal fulminant hepatitis associated with INH. Drug interactions were systemically searched for. Three probably led to clinical manifestations: they implicated INH with carba...
Thérapie
Intravenous immunoglobulin (IVIG) is currently used for an increasing number of indications where... more Intravenous immunoglobulin (IVIG) is currently used for an increasing number of indications where an immune-medicated disorder is suspected. It is considered as a safe and efficacious treatment but several cases of severe acute renal failure (ARF) have been described since 1987. We report four cases of IVIG-induced ARF and the literature on the subject is reviewed. The chronological and semiological characteristics of this rare adverse effect are analysed. A sudden and marked increase of serum creatinine within the 2 to 4 days following institution of IVIG therapy, especially when the patient becomes oligo-anuric, is very suggestive of IVIG renal toxicity. The recovery of renal function is often obtained in 10 to 15 days after discontinuation of the drug. Histological changes are characterized by osmotic nephrosis injuries. Patients generally presented numerous risk factors such as over 65 years, particularly in men, pre-existing renal disease, long-standing diabetes mellitus or hyp...
Thérapie
Pseudomembranous colitis (PMC) is a rare but potentially severe complication of antibiotic treatm... more Pseudomembranous colitis (PMC) is a rare but potentially severe complication of antibiotic treatment, which is characterized by the proliferation of the bacterium Clostridium difficile in the colon. In this retrospective study, 48 cases of endoscopically confirmed PMC were included. The following variables were analysed: characteristics of the patients, antibiotics, clinical, biological and endoscopic features of PMC and its treatment. The antibiotic treatment was often ambulatory (83 per cent) for a broncho-pulmonary infection (42 per cent). In 90 per cent of the cases, the treatment included a -lactam, frequently amoxicillin with clavulanic acid, and in 25 per cent of the cases, a fluoroquinolone. The PMC generally occurred after more than 4 days of treatment and was associated with diarrhoea, abdominal pain, fever and rarely vomiting (23 per cent). The complications were hypokalaemia (37 per cent), renal failure (27 per cent) and/or hypoproteinaemia (50 per cent). Pseumembranes w...
Gastroentérologie Clinique et Biologique
Gastroentérologie Clinique et Biologique
Thérapie
This case report concerns a woman treated continuously since at least 10 years by methysergide fo... more This case report concerns a woman treated continuously since at least 10 years by methysergide for cluster headache. The echocardiographic and histological features of the severe valve fibrosis presented by this patient are very similar to those described with 5 HT2B receptors agonistic drugs.
Pharmacoepidemiology and Drug Safety
Benfluorex is responsible for the development of restrictive valvular regurgitation due to one of... more Benfluorex is responsible for the development of restrictive valvular regurgitation due to one of its metabolites, norfenfluramine. The 5-HT2B receptor, expressed on heart valves, acts as culprit receptor for drug-induced valvular heart disease (VHD). Stimulation of this receptor leads to the upregulation of target genes involved in the proliferation and stimulation of valvular interstitial cells through different intracellular pathways. Valve lesions essentially involve the mitral and/or aortic valves. The randomised prospective REGULATE trial shows a threefold increase in the incidence of valvular regurgitation in patients exposed to benfluorex. A cross-sectional trial shows that about 7% of patients without a history of VHD previously exposed to benfluorex present echocardiographic features of drug-induced VHD. The excess risks of hospitalisation for cardiac valvular insufficiency and of valvular replacement surgery were respectively estimated to 0.5 per 1000 and 0.2 per 1000 exp...
Presse médicale (Paris, France : 1983), Jan 7, 2003
Thérapie
The major risk of oral anticoagulant therapy is haemorrhage potentially affecting all organs. Ble... more The major risk of oral anticoagulant therapy is haemorrhage potentially affecting all organs. Bleeding in the central nervous system is a rare but severe complication of anticoagulant therapy. This study aimed to analyse a series of intracranial haemorrhages. This series from the Regional Pharmacovigilance Center of Amiens included spontaneously reported and retrospectively collected cases from January 1999 to December 2000. During this period, 38 cases of intracranial bleeding possibly related to oral anticoagulant administration were reported; 19 women and 19 men, median age 69.5 (29 to 87) years. In 34% of the cases, patients died and in 18% neurologic sequelae were still present at the time of the evaluation. In 21 cases (62%), the INR (International Normalized Ratio) was higher than the therapeutic range recommended for the indication. Among the most frequent risk factors, hypertension and recent minor trauma are highlighted in this series. In 17 cases, oral anticoagulants were...
European Journal of Echocardiography, 2010
To investigate the association between benfluorex use and organic restrictive mitral regurgitatio... more To investigate the association between benfluorex use and organic restrictive mitral regurgitation (MR) in patients admitted to hospital for diagnostic work-up of MR of unclear aetiology. Among patients referred between 2003 and 2008 to our tertiary centre for diagnostic work-up of MR, we retrospectively identified 22 consecutive patients (65 +/- 12 years, 64% women) with restrictive organic MR of unclear aetiology. Using propensity scores, 22 out of 156 patients who underwent surgery for dystrophic MR due to flail leaflets during the same time period were matched for age, sex, height, body weight, and diabetes with the study population. Eight of the 22 patients with restrictive organic MR of unclear aetiology (36.4%) had a history of benfluorex use, and in one patient (4.5%) we identified previous exposure to both benfluorex and fenfluramine. The frequency of benfluorex treatment in patients with restrictive organic MR of unclear aetiology was significantly higher compared with that observed in the dystrophic MR group (36.4 vs. 4.5%; P-value 0.039). Patients with restrictive MR treated with benfluorex (body mass index 31 +/- 6 kg/m(2)) were all dyslipidaemic and 67% had diabetes. Echocardiography identified moderate or severe restrictive organic MR in all cases. Median total duration of benfluorex therapy was 63(12-175) months, at a daily dose of 450 (300-450) mg, leading to a cumulative dose of 850 (108-2363) g. Although it cannot affirm a definitive causal relationship, the present study strongly suggests that patients treated with benfluorex might incur a risk of restrictive organic valvular heart disease. Therefore, echocardiography should be performed in patients exposed to benfluorex in case of occurrence of symptoms or signs of valvular disease. Further data are needed to confirm these findings.
Thérapie, 2014
This case report concerns a woman treated continuously since at least 10 years by methysergide fo... more This case report concerns a woman treated continuously since at least 10 years by methysergide for cluster headache. The echocardiographic and histological features of the severe valve fibrosis presented by this patient are very similar to those described with 5 HT(2B) receptors agonistic drugs.
Circulation, 2009
Background-Chronic renal failure (CRF) is associated with cardiac dysfunction and increased aorti... more Background-Chronic renal failure (CRF) is associated with cardiac dysfunction and increased aortic stiffness. The mechanisms involved are not clearly understood. We examined changes over time in cardiac and aortic function in a murine CRF model. Methods and Results-Eight-week-old mice were randomly assigned to 1 of 4 groups: wild-type non-CRF, wild-type CRF, apolipoprotein E knockout non-CRF, and apolipoprotein E knockout CRF. Echocardiography was performed and blood samples were taken at baseline and after 6 and 10 weeks of CRF. Vascular reactivity and adhesion molecule expression were studied after 6 and 10 weeks of CRF. Left ventricular hypertrophy, altered left ventricular relaxation, and increased aortic stiffness were observed after 6 weeks of CRF and persisted after 10 weeks. The 4 groups of mice did not significantly differ in terms of arterial blood pressure and aortic structure. The degree of vascular calcification and serum total cholesterol concentration were higher in the CRF groups than in the non-CRF groups. These changes, however, could not explain the cardiac and vascular differences seen in the 2 CRF groups. In contrast, alterations in vascular reactivity, the upregulation of adhesion molecule expression, and CRF status were significantly associated with these changes. Conclusions-In a mouse model of CRF, left ventricular hypertrophy, cardiac diastolic dysfunction, and increased aortic stiffness were not related to structural changes in the aorta (including aortic calcification) or high serum cholesterol levels. However, cardiac and aortic abnormalities were associated with the extent of subendothelial dysfunction and the severity of CRF. (Circulation. 2009;119:306-313.)
British journal of clinical pharmacology, Jan 2, 2015
Voriconazole (VRC) is mainly metabolized by CYP2C19 and CYP3A4 and exhibits a wide inter- and int... more Voriconazole (VRC) is mainly metabolized by CYP2C19 and CYP3A4 and exhibits a wide inter- and intra-individual variability requiring therapeutic drug monitoring (TDM). We present a case of VRC therapy failure in a patient carrying a CYP2C19*17/*17 genotype. A 26-year-old Caucasian woman treated for an acute leukemia developed a neutropenic fever associated to a respiratory distress. Seventeen days after the introduction of a standard VRC antifungal treatment, she suffered from cough and hemoptysis, detection of fungal blood markers remained positive and chest high-resolution CT scan revealed newer lesions in lungs, suggesting a refractory aspergillosis. After a 2-hour intravenous infusion of 400mg dose, VRC concentrations were 3.48, 1.10, 0.22 and 0.17 mg/L at 2, 4, 8 and 12 hours respectively. Area under the concentration time curve from zero to infinity, clearance and terminal half-life were estimated at 11.1 h.mL/min, 35.9 L/h and 2.3 h respectively. The concentration ratio of th...
Thérapie
Veralipride is a substituted benzamide which is used for the treatment of menopausal hot flushes.... more Veralipride is a substituted benzamide which is used for the treatment of menopausal hot flushes. We report five cases with extrapyramidal disorders associated to a treatment with this drug for which the neuroleptic activity resulting from an interaction with D2 receptors is not always known by prescribers. One case consisted of acute dyskinesias and four of parkinsonian syndromes, one of these being associated with tardive dyskinesia. In these four cases, dosing recommendations were not respected.
Thérapie
Interferon alfa (INF alpha), which is used in chronic active viral hepatitis, presents some safet... more Interferon alfa (INF alpha), which is used in chronic active viral hepatitis, presents some safety problems. Side effects observed in 72 treated patients with chronic active hepatitis C are analysed in this retrospective study. Doses used were 3 or 9 M IU, three times a week, for 12 to 24 weeks. There were no contra-indications to the treatment and all patients had the factors predictive of a satisfactory therapeutic response. Apart from general debility, there were side effects in 65 of the 72 patients as follows: flu-like syndrome (n = 39), gastrointestinal (n = 29), dermatological (n = 24), haematological (n = 23), neurological (n = 20), cardiovascular (n = 6) and thyroid (n = 6) disorders. For 30 per cent of the patients, the dose was decreased (n = 6) or the treatment was withdrawn, temporarily (n = 5) or permanently (n = 10). These results are in accordance with those published and emphasize the need for clinico-biological monitoring during and after treatment. Indeed delayed ...
Thérapie
Management of tuberculosis in a hospital environment is well systematized and may include chemopr... more Management of tuberculosis in a hospital environment is well systematized and may include chemoprophylaxis, which may be hazardous when used in psychiatric impairments. We examined retrospectively adverse events occurring during a 6-month period of antituberculosis treatment. Besides patients initially treated for active pulmonary tuberculosis, 16 other patients have benefited from chemoprophylaxis with isoniazid (INH) and/or rifampicin (RFP). All these patients (mean age 53 years) had been institutionalized for several years. Fifteen of them still received a mean of 5.4 +/- 2.2 drugs including 3.3 +/- 1.4 psychotropic agents. During antituberculous treatment, 5 patients (29 per cent) presented side effects: hyperuricaemia with pyrazinamide, neutropenia, dysphagia and anorexia, dizziness and falls, diabetes and fatal fulminant hepatitis associated with INH. Drug interactions were systemically searched for. Three probably led to clinical manifestations: they implicated INH with carba...
Thérapie
Intravenous immunoglobulin (IVIG) is currently used for an increasing number of indications where... more Intravenous immunoglobulin (IVIG) is currently used for an increasing number of indications where an immune-medicated disorder is suspected. It is considered as a safe and efficacious treatment but several cases of severe acute renal failure (ARF) have been described since 1987. We report four cases of IVIG-induced ARF and the literature on the subject is reviewed. The chronological and semiological characteristics of this rare adverse effect are analysed. A sudden and marked increase of serum creatinine within the 2 to 4 days following institution of IVIG therapy, especially when the patient becomes oligo-anuric, is very suggestive of IVIG renal toxicity. The recovery of renal function is often obtained in 10 to 15 days after discontinuation of the drug. Histological changes are characterized by osmotic nephrosis injuries. Patients generally presented numerous risk factors such as over 65 years, particularly in men, pre-existing renal disease, long-standing diabetes mellitus or hyp...
Thérapie
Pseudomembranous colitis (PMC) is a rare but potentially severe complication of antibiotic treatm... more Pseudomembranous colitis (PMC) is a rare but potentially severe complication of antibiotic treatment, which is characterized by the proliferation of the bacterium Clostridium difficile in the colon. In this retrospective study, 48 cases of endoscopically confirmed PMC were included. The following variables were analysed: characteristics of the patients, antibiotics, clinical, biological and endoscopic features of PMC and its treatment. The antibiotic treatment was often ambulatory (83 per cent) for a broncho-pulmonary infection (42 per cent). In 90 per cent of the cases, the treatment included a -lactam, frequently amoxicillin with clavulanic acid, and in 25 per cent of the cases, a fluoroquinolone. The PMC generally occurred after more than 4 days of treatment and was associated with diarrhoea, abdominal pain, fever and rarely vomiting (23 per cent). The complications were hypokalaemia (37 per cent), renal failure (27 per cent) and/or hypoproteinaemia (50 per cent). Pseumembranes w...
Gastroentérologie Clinique et Biologique
Gastroentérologie Clinique et Biologique
Thérapie
This case report concerns a woman treated continuously since at least 10 years by methysergide fo... more This case report concerns a woman treated continuously since at least 10 years by methysergide for cluster headache. The echocardiographic and histological features of the severe valve fibrosis presented by this patient are very similar to those described with 5 HT2B receptors agonistic drugs.
Pharmacoepidemiology and Drug Safety
Benfluorex is responsible for the development of restrictive valvular regurgitation due to one of... more Benfluorex is responsible for the development of restrictive valvular regurgitation due to one of its metabolites, norfenfluramine. The 5-HT2B receptor, expressed on heart valves, acts as culprit receptor for drug-induced valvular heart disease (VHD). Stimulation of this receptor leads to the upregulation of target genes involved in the proliferation and stimulation of valvular interstitial cells through different intracellular pathways. Valve lesions essentially involve the mitral and/or aortic valves. The randomised prospective REGULATE trial shows a threefold increase in the incidence of valvular regurgitation in patients exposed to benfluorex. A cross-sectional trial shows that about 7% of patients without a history of VHD previously exposed to benfluorex present echocardiographic features of drug-induced VHD. The excess risks of hospitalisation for cardiac valvular insufficiency and of valvular replacement surgery were respectively estimated to 0.5 per 1000 and 0.2 per 1000 exp...
Presse médicale (Paris, France : 1983), Jan 7, 2003
Thérapie
The major risk of oral anticoagulant therapy is haemorrhage potentially affecting all organs. Ble... more The major risk of oral anticoagulant therapy is haemorrhage potentially affecting all organs. Bleeding in the central nervous system is a rare but severe complication of anticoagulant therapy. This study aimed to analyse a series of intracranial haemorrhages. This series from the Regional Pharmacovigilance Center of Amiens included spontaneously reported and retrospectively collected cases from January 1999 to December 2000. During this period, 38 cases of intracranial bleeding possibly related to oral anticoagulant administration were reported; 19 women and 19 men, median age 69.5 (29 to 87) years. In 34% of the cases, patients died and in 18% neurologic sequelae were still present at the time of the evaluation. In 21 cases (62%), the INR (International Normalized Ratio) was higher than the therapeutic range recommended for the indication. Among the most frequent risk factors, hypertension and recent minor trauma are highlighted in this series. In 17 cases, oral anticoagulants were...
European Journal of Echocardiography, 2010
To investigate the association between benfluorex use and organic restrictive mitral regurgitatio... more To investigate the association between benfluorex use and organic restrictive mitral regurgitation (MR) in patients admitted to hospital for diagnostic work-up of MR of unclear aetiology. Among patients referred between 2003 and 2008 to our tertiary centre for diagnostic work-up of MR, we retrospectively identified 22 consecutive patients (65 +/- 12 years, 64% women) with restrictive organic MR of unclear aetiology. Using propensity scores, 22 out of 156 patients who underwent surgery for dystrophic MR due to flail leaflets during the same time period were matched for age, sex, height, body weight, and diabetes with the study population. Eight of the 22 patients with restrictive organic MR of unclear aetiology (36.4%) had a history of benfluorex use, and in one patient (4.5%) we identified previous exposure to both benfluorex and fenfluramine. The frequency of benfluorex treatment in patients with restrictive organic MR of unclear aetiology was significantly higher compared with that observed in the dystrophic MR group (36.4 vs. 4.5%; P-value 0.039). Patients with restrictive MR treated with benfluorex (body mass index 31 +/- 6 kg/m(2)) were all dyslipidaemic and 67% had diabetes. Echocardiography identified moderate or severe restrictive organic MR in all cases. Median total duration of benfluorex therapy was 63(12-175) months, at a daily dose of 450 (300-450) mg, leading to a cumulative dose of 850 (108-2363) g. Although it cannot affirm a definitive causal relationship, the present study strongly suggests that patients treated with benfluorex might incur a risk of restrictive organic valvular heart disease. Therefore, echocardiography should be performed in patients exposed to benfluorex in case of occurrence of symptoms or signs of valvular disease. Further data are needed to confirm these findings.
Thérapie, 2014
This case report concerns a woman treated continuously since at least 10 years by methysergide fo... more This case report concerns a woman treated continuously since at least 10 years by methysergide for cluster headache. The echocardiographic and histological features of the severe valve fibrosis presented by this patient are very similar to those described with 5 HT(2B) receptors agonistic drugs.