Endoscopic variceal ligation in prophylaxis of first variceal bleeding in cirrhotic patients with high-risk esophageal varices.

To determine the efficacy of endoscopic variceal ligation (EVL) in prophylaxis on the rate of first esophageal variceal bleeding, we conducted a prospective, randomized trial in 126 cirrhotic patients with no history of previous upper gastrointestinal bleeding and with esophageal varices endoscopically judged to be at high risk of hemorrhage. The end-points of the study were bleeding and death. Life-table curves showed that prophylactic EVL significantly diminished the rate of variceal hemorrhage (12/62 [19%] vs. 38/64 [60%]; P = .0001) and overall mortality (17/62 [28%] vs. 37/64 [58%]; P = .0011). The 2-year cumulative bleeding rate was 19% (12/ 62) in the EVL group and 60% (38/64) in the control group. The 2-year cumulative mortality rate was 28% (17/62) in the EVL group and 58% (37/64) in the control group. Comparison of Kaplan-Meier estimates of the time to death of both groups showed significantly lower mortality in the ligation group (P = .001). Patients undergoing EVL had few treatment failures and died mainly of hepatic failure. The lower risk in the EVL group was attributed to a rapid reduction of variceal size. Prophylactic EVL was more efficient in preventing first bleeding in patients with good condition (Child A) than in those with decompensated disease (Child B and C). We conclude that prophylactic EVL can decrease the incidence of first variceal bleeding and death over a period of 2 years in cirrhotic patients with high-risk esophageal varices.

Doridosine derivatives: binding at adenosine receptors and in vivo effects.

Doridosine, an adenosine analogue, causes, in vivo, hypotension, reduction of heart rates, muscle relaxation and anti-inflammatory effects through adenosine A1 and A2 receptors. A series of doridosine derivatives was synthesized in a search for compounds with more selective adenosine A1 receptor activity. These derivatives were characterized for binding to the respective adenosine receptors and for their cardiovascular effects. We used competition binding studies with highly selective radioligands: [3H]cyclohexyladenosine for adenosine A1 and [3H]CGS 21680 for adenosine A2 binding assays. The results for eight doridosine derivatives revealed that 1-cyclopropylisoguanosine (BN-063) and 1-allylisoguanosine (AZ-108-1) were more selective for the adenosine A1 receptor. In vivo, both BN-063 and AZ-108-1 caused significant bradycardia but no obvious effect on blood pressure. The bradycardia was almost completely blocked by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, a specific adenosine A1 receptor antagonist).