Azizi M.,Center dinvestigations cliniques
Bulletin de l'Academie Nationale de Medecine | Year: 2014
Blockade of the renin-angiotensin system (RAS) with angiotensin-converting-enzyme (ACEI) inhibitors or angiotensin II receptor blockers (ARB) has become a major therapeutic tool. Due to internal counter-regulation, however, this system cannot be fully blocked by targeting only one of its components. Instead of increasing the doses of an ACEI, an A RB or a renin inhibitor, blocking RAS at two successive levels neutralizes the consequences of internal counter-regulation and thus provides a more complete blockade with more pronounced biological effects. Additive effects on blood pressure lowering and on renin secretion during combined administration of RAS blockers were first demonstrated in normotensive subjects and in various experimental models of hypertension, heart failure and renal failure. Although combined RAS blockade provided an additional hemodynamic response and more complete neutralization of the cellular effects of angiotensin II, no benefit was observed in terms of cardiovascular or renal protection in heart disease (heart failure, post-myocardial infarction, high vascular risk) or kidney disease (diabetic nephropathy). Moreover, more complete RAS blockade is risky in conditions where blood pressure and renal perfusion are renin-dependent (renal failure and hypotension) and also in hypoaldosteronism (hyperkalemia). The European, French and U.S. health agencies have contraindicated combined RAS blockade because of its unfavorable risk-benefit balance, especially in patients with diabetes or renal failure.
Steichen O.,Center dinvestigations cliniques |
Amar L.,University of Paris Descartes |
Plouin P.-F.,University of Paris Descartes
Journal of Vascular Surgery | Year: 2010
Introduction: Endovascular treatment for atherosclerotic renal artery stenosis (ARAS) was first performed >30 years ago and its use has increased rapidly since then. However, only recently have large randomized trials rigorously evaluated its clinical benefit. Methods: We systematically reviewed the controlled studies on primary stenting for atherosclerotic renal artery stenosis. Studies were included if they compared the outcome of stenting with other treatments, or the outcome associated with different stent characteristics or stenting methods. Results: Stenting is preferred over angioplasty alone and over surgery when revascularization is indicated for ostial ARAS, except in cases of coexistent aortic disease indicating surgery. Randomized controlled trials showed no significant benefit and substantial risk of renal artery stenting over medication alone in patients with atherosclerotic ARAS without a compelling indication. Improvements in the procedure, such as with distal embolic protection devices and coated stents, are not associated with better clinical outcomes after stent placement for ARAS. Conclusion: Recent evidence shows that impaired renal function associated with ARAS is more stable over time than previously observed. Optimal medical treatment should be the preferred option for most patients with ARAS. Only low-level evidence supports compelling indications for revascularization in ARAS, including rapidly progressive hypertension or renal failure and flash pulmonary edema. © 2010 Society for Vascular Surgery.
Silver R.T.,Myeloproliferative Disease Center |
Kiladjian J.-J.,Center dinvestigations cliniques |
Kiladjian J.-J.,University Paris Diderot |
Hasselbalch H.C.,Copenhagen University
Expert Review of Hematology | Year: 2013
Recombinant IFN-α (rIFN-α) induces complete hematologic remissions in patients with myeloproliferative neoplasms (MPNs), but its use has been limited by side effects owing to the relatively high doses used. Now, low-dose rIFN-α is stressed, starting relatively early in the course of the MPNs. In polycythemia vera, this has resulted in a significant clinical, hematologic, morphologic and molecular response manifested by reduction in the JAK2V617F allele burden, sustained even after discontinuation of recombinant IFN. In essential thrombocythemia, platelet count reduction is prompt and durable without treatment for varying periods. In hypercellular primary myelofibrosis, rIFN-α has restored normal blood counts, reduced splenomegaly and induced morphologic marrow remissions. This article highlights our current use of rIFN-α in MPNs. © 2013 Expert Reviews Ltd.
Campbell P.J.,Wellcome Trust Sanger Institute |
Campbell P.J.,University of Cambridge |
MacLean C.,Addenbrookes Hospital |
MacLean C.,University of Cambridge |
And 9 more authors.
Blood | Year: 2012
Essential thrombocythemia, a myeloproliferative neoplasm, is associated with increased platelet count and risk of thrombosis or hemorrhage. Cytoreductive therapy aims to normalize platelet counts despite there being only a minimal association between platelet count and complication rates. Evidence is increasing for a correlation between WBC count and thrombosis, but prospective data are lacking. In the present study, we investigated the relationship between vascular complications and 21 887 longitudinal blood counts in a prospective, multicenter cohort of 776 essential thrombocythemia patients. After correction for confounding variables, no association was seen between blood counts at diagnosis and future complications. However, platelet count outside of the normal range during follow-up was associated with an immediate risk of major hemorrhage (P = .0005) but not thrombosis (P = .7). Elevated WBC count during follow-up was correlated with thrombosis (P = .05) and major hemorrhage (P = .01). These data imply that the aim of cytoreduction in essential thrombocythemia should be to keep the platelet count, and arguably the WBC count, within the normal range. This study is registered at the International Standard Randomized Controlled Trials Number Registry (www.isrctn.org) as number 72251782. © 2012 by The American Society of Hematology.
Blanchard A.,University of Paris Descartes |
Blanchard A.,Center dinvestigations cliniques |
Vargas-Poussou R.,University of Paris Descartes
Nephrologie et Therapeutique | Year: 2012
Extracellular content in magnesium represents about 1% of total body content, of which plasma magnesium is thus a poor reflect. Hypomagnesaemia is defined by a value lesser than 0.65 mmol/L. Its incidence in hospitalized patients ranges between 10 and 15%. Identification of the physiopathology of hypomagnesaemia relies first upon concomitant measurement of plasma and urinary magnesium concentration. Daily magnesium excretion lesser than 1 mmol/L or EFMg lesser than 1% sign extra renal origin, due to either low magnesium intake, low intestinal absorption of magnesium or derivation of extracellular magnesium toward bone, such as in bone reparation process after hyperparathyroidism surgery. Daily magnesium excretion higher than 2 mmol/L concomitant to hypomagnesaemia indicates native or acquired renal loss of magnesium. Congenital renal and extra-renal losses of magnesium are mainly related to rare monogenic disease, and are inconstantly associated with a renal loss of sodium, potassium and calcium. Recent progress in the genetics of this rare diseases have greatly improved the knowledge about proteins involved in intestinal abortion, renal renal tubular re-absorption of magnesium and its regulations. Hypermagnesemia is a rarer metabolic disorder than hypomagnesemia (about 5% of hospitalized patients). Asymptomatic below 2 mmol/L, it progressively alters neuromuscular transmission, autonomic sympathic activity and cardiac conduction, with vital risk above 7 mol/L. It is due to acute magnesium input into extracellular volume most often associated with a decrease in glomerular filtration rate, limiting the high physiological ability to excrete magnesium input. © 2012 Association Société de néphrologie. Publiépar Elsevier Masson SAS. Tous droits réservés.