Philosophie zoologique; ou, Exposition des considérations relatives à l'histoire naturelle des animaux. Nouv. éd., rev. et précédée d'une introd. biographique par Charles Martins

Carvedilol for preventing recurrent variceal bleeding: Waiting for convincing evidence

“…These unique properties mean that carvedilol can reduce portal pressure both by decreasing portal-collateral blood flow (as all other NSBBs) and by diminishing the functional component of hepatic vascular resistance (the hepatic vascular tone) that is increased in cirrhosis and contributes to portal pressure elevation. 1 Because of these combined effects, carvedilol has the potential of causing a more-pronounced decrease in portal pressure than propranolol or nadolol, the current standard NSBBs for the treatment of PH. However, because its vasodilatory effect is not liver selective, carvedilol carries the risk of causing or intensifying systemic hypotension, a drawback for any vasodilator in patients with advanced cirrhosis because it may enhance sodium retention.…”

“…However, because its vasodilatory effect is not liver selective, carvedilol carries the risk of causing or intensifying systemic hypotension, a drawback for any vasodilator in patients with advanced cirrhosis because it may enhance sodium retention. 1,2 Previous studies in patients with cirrhosis indeed demonstrated that carvedilol causes greater falls in portal pressure than propranolol, and that this effect is achieved with relatively low doses (12.5-25.0 mg/day) that usually do not cause systemic hypotension and are well tolerated. [1][2][3] Reduction of the hepatic venous pressure gradient (HVPG) in these studies ranged between 16% and 43% with carvedilol versus 12%-13% with propranolol.…”

“…1,2 Previous studies in patients with cirrhosis indeed demonstrated that carvedilol causes greater falls in portal pressure than propranolol, and that this effect is achieved with relatively low doses (12.5-25.0 mg/day) that usually do not cause systemic hypotension and are well tolerated. [1][2][3] Reduction of the hepatic venous pressure gradient (HVPG) in these studies ranged between 16% and 43% with carvedilol versus 12%-13% with propranolol. Because the clinical efficacy of NSBBs decreasing the risk of variceal bleeding or rebleeding is tightly correlated with their capacity of decreasing the HVPG by more than 20% of baseline values or below 12 mmHg, 4 the available evidence strongly suggested that carvedilol had potential to achieve better clinical results than propranolol/nadolol and thus was well suited to be used in randomized, controlled trials (RCTs) for PH.…”

“…Because the clinical efficacy of NSBBs decreasing the risk of variceal bleeding or rebleeding is tightly correlated with their capacity of decreasing the HVPG by more than 20% of baseline values or below 12 mmHg, 4 the available evidence strongly suggested that carvedilol had potential to achieve better clinical results than propranolol/nadolol and thus was well suited to be used in randomized, controlled trials (RCTs) for PH. 1 The fact that only two relatively small RCTs with clinical endpoints have been performed so far probably reflects the difficulties in conducting investigator-initiated RCTs, because the pharma companies did not sponsor therapeutic studies using carvedilol in patients with cirrhosis. The funding difficulties encountered explain some of the limitations of these studies that go from the lack of HVPG measurements to being open comparisons of carvedilol versus other treatments, instead of double-blind face-to-face comparison versus other NSBBs, alone or on top of endoscopic therapy.…”

Revisiting Crick?s Dogma and the Impossibility of Reverse Translation

“…The possible existence of a protein > DNA order of information transfer could revitalize Lamarckism [26], which held that acquired characteristics might become inherited. We all know that Lamarck's ideas were thoroughly tested in practice by Lysenko [27], causing widespread death from hunger in his country.…”