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Biomedical subjects

J P Pascal

Publications and source records attributed to J P Pascal.

At least 37 records · Page 2Linked to original sources
PubMed1996

Haemodynamic effects of molsidomine and propranolol in patients with cirrhosis.

Propranolol and molsidomine have both been shown to decrease the hepatic venous pressure gradient in patients with cirrhosis. The present study aimed at assessing the effects of the combination of these two drugs on splanchnic and systemic haemodynamics of cirrhotic patients. Fifteen patients with biopsy proven alcoholic cirrhosis had haemodynamic measurements under basal conditions, 60 min after oral administration of 4 mg molsidomine then 15 min after intravenous administration of 15 mg propranolol. As compared with baseline values, molsidomine was found to decrease mean arterial pressure (-7.9%, (P < 0.01), cardiac output (-7.3%, P < 0.01), pulmonary wedged pressure (-45.8%, (P < 0.05) and hepatic venous pressure gradient (-11.7%, P < 0.01). Propranolol decreased heart rate (-21%, P < 0.01), further decreased cardiac output (-20.6%, (P < 0.01) and hepatic venous pressure gradient (-10.5%, P < 0.01). As a whole, molsidomine plus propranolol decreased mean arterial pressure (-8%, P < 0.01), heart rate (-19%, P < 0.01), cardiac output (-26.5%, P < 0.01) and hepatic venous pressure gradient (-21%, P < 0.01). Pulmonary wedged pressure, liver blood flow and hepatic intrinsic clearance of indocyanine green were not significantly changed by the association of molsidomine and propranolol. We conclude that in patients with cirrhosis, molsidomine and propranolol potentiate their effects on hepatic venous pressure gradient. Such a combination could therefore prove useful in the treatment of portal hypertension.

Adrenergic beta-Antagonists↗
PubMed1995

[Transmission and prevention of viral hepatitis].

The ways of transmission of hepatotropic viruses are now fairly known. Populations at risk for these infections are precisely identified and preventive measures are efficient. Safe hygiene for oro-fecal as well as for sexual or blood transmission is accurately determined. Vaccines exist against some viruses. In the future, efforts will have to be made in several directions: a) education of individuals at risk, in order to further diminish the transmission of the viruses in these groups; b) identification of the mode of transmission of sporadic hepatitis which, so far, has escaped any prevention; c) design of a vaccine against virus C, which will make mass prevention possible.

Hepatitis A↗
PubMed1995

Weakness of mucosal barrier in portal hypertensive gastropathy of alcoholic cirrhosis. Effects of propranolol and enprostil.

BACKGROUND/AIMS: It has been suggested that the vulnerability of gastric mucosa is increased in patients with cirrhosis as a result of a PGE2 deficiency. Therefore, we evaluated whether PGE2 mucosal generation, and gastric potential difference - a reflection of the gastric mucosal barrier - were correlated to endoscopic features and whether these alterations could be alleviated. METHODS: The potential difference was measured before (basal) and after a stimulation test by aspirin. The serum levels of gastrin and glucagon were also determined. Finally, the effects of a 1-week administration of propranolol or enprostil were tested on potential difference. The endoscopic grade of portal hypertensive gastropathy was assessed according to McCormack et al. The results are presented respectively for controls, patients with mild gastropathy, and patients with severe gastropathy. Comparisons were made using variance or covariance analysis after adjustment with age. RESULTS: Basal potential difference was significantly different between the three groups: -30.6, -28.8, -24.9 mV, p <0.05, respectively. The effects of aspirin administration on potential difference parameters were significantly different between the three groups (irritability index: 35 +/- 25, 92 +/- 98, 114 +/- 74 mV2.min, p <0.05, respectively) when non-responders to aspirin were excluded. PGE2 mucosal generation was significantly increased in both the antrum (9.8, 19.5, 19.7 ng/mg proteins, p<0.05, respectively) and in the corpus (8.1, 14.0, 20.2 ng/mg proteins, p<0.05, respectively). PGE2 generation was not related to potential difference. Glucagon serum levels were related to the grade of gastropathy. A 1-week administration of 160 mg/d long-acting propranolol, 35 micro g/d enprostil or placebo did not significantly modify basal potential difference. CONCLUSIONS: Portal hypertensive gastropathy is characterized by a decreased potential difference proportional to the endoscopic severity. The gastric mucosa of patients with cirrhosis seems to be more susceptible to aspirin than that of healthy subjects. It appears that the role of PGE2 is controversial in portal hypertensive gastropathy. Propranolol and enprostil do not improve this decreased potential difference.

Adrenergic beta-Antagonists↗
PubMed1994

[Enterovenous fistula. An unusual complication of Crohn disease].

We report a case of enterovenous fistula in a young 22-year-old patient with Crohn's disease associated with jaundice. Ultrasound and computed tomography showed stationary gaz and barium in the liver. Pathological examination showed a fistula between the lumen of the inflamed segment of the ileum and the superior mesenteric venous system. This unusual finding in Crohn's disease may be a severe complication.

Adult↗
PubMed1993

Hemodynamic and pharmacokinetic study of tertatolol in patients with alcoholic cirrhosis and portal hypertension.

Tertatolol, a recently developed beta 1-beta 2-blocker has two advantages: it does not induce withdrawal syndrome after abrupt cessation, and it preserves renal function. It has been suggested that the kinetics of tertatolol in patients with hepatic dysfunction are altered. Therefore, the hemodynamic effects and pharmacokinetics following the acute administration of tertatolol were studied in cirrhotic patients with portal hypertension. Systemic, splanchnic and renal hemodynamics were evaluated before and 30 min after the simultaneous administration of 2.5 mg tertatolol p.o. and 1.25 mg deuterated tertatolol i.v. in 10 cirrhotic patients with esophageal varices. The pharmacokinetics of tertatolol were evaluated over a 4-day period. Tertatolol significantly decreased heart rate (-22 +/- 10%), cardiac output (-26 +/- 8%), and hepatic blood flow (-27 +/- 23%). The hepatic venous pressure gradient decreased from 15.7 +/- 5.0 to 12.9 +/- 4.0 mmHg (-17 +/- 13%, P < 0.01). Three out of 10 patients were non-responders to tertatolol. Renal blood flow (-9 +/- 28%) and intrinsic hepatic clearance of indocyanin green (-9 +/- 25%) were not significantly modified. The duration of effective beta-blockade was far less than 12 h. Tertatolol was rapidly absorbed with a Cmax of 70 +/- 51 micrograms/l at a peak time of 0.75 +/- 0.26 h. In comparison with healthy volunteers referred to in literature sources, plasma clearance was reduced to 49 +/- 28 ml/min, bioavailability was increased to 72 +/- 20%, and the volume of distribution was increased to 50 +/- 34 l, probably due, in part, to a weaker protein binding -85%--effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1993

Diffuse vascular ectasia of the antrum, duodenum, and jejunum in a patient with nodular regenerative hyperplasia. Lack of response to portosystemic shunt or gastrectomy.

The case is reported of a 70 year old man who presented with severe anaemia because of chronic gastrointestinal blood loss. This loss was ascribed to vascular ectasia resembling the gastric antral vascular ectasia syndrome but extended to include the antrum, the duodenum, the jejunum, and, possibly, the cardiac area. This condition was associated with portal hypertension as a result of nodular regenerative hyperplasia. Consecutive treatments including sucralfate, prostaglandin E2, propranolol, organic nitrates, pentoxyphilline, corticosteroids, endoscopic sclerotherapy, portosystemic shunt, total gastrectomy, proved ineffective.

Aged↗
PubMed1993

[Treatment of hemorrhages by rupture of cardio-tuberous varices with transjugular intrahepatic portasystemic shunt].

Twelve consecutive patients admitted for bleeding from ruptured gastric varices were treated with transjugular intrahepatic portosystemic shunts and followed for a mean of 6 +/- 3 months (range: 8-293 days). The shunt was performed successfully in all 12 patients. The shunt occluded in 3 patients (respectively 19, 101 and 103 days after insertion) of whom one remained asymptomatic and two experienced rebleeding. Four patients presented with acute encephalopathy, spontaneously in two and after rebleeding in two. Three patients died, two after rebleeding and one of septic shock secondary to pneumonia. Overall, 9 patients survived a mean of 211 +/- 92 days with no rebleeding, 8 of whom have not yet experienced any complications. These results suggest that transjugular intrahepatic portosystemic shunts could be useful in treating hemorrhages from ruptured gastric varices and in preventing their recurrence.

Adult↗
PubMed1992

[Evaluation of the effects of molsidomine and propranolol-molsidomine combination on portal hemodynamics by pulsed Doppler ultrasound].

Molsidomine, a long acting vasodilator with antianginal properties, has been shown to decrease porto-hepatic pressure gradient in patients with cirrhosis. The present study aimed at assessing the effects of molsidomine, propranolol and of the association of these two drugs on portal vein blood flow as measured using Doppler and B-mode sonography. In 10 patients without liver disease (group 1), portal flow time average mean velocity (TAV) and portal vein blood flow (PVBF) were measured under basal conditions, 1 hour then 2 hours after ingestion of 4 mg of molsidomine. The same measurements were performed in 15 patients with cirrhosis (group 2) under basal conditions, 1 then 2 hours after double-blind administration of either molsidomine (10 patients) or placebo (5 patients). Fifteen further patients with cirrhosis (group 3) were studied after the double blind administration of 80 mg of propranolol and two hours later of 4 mg of molsidomine (10 patients) or placebo (5 patients); TAV and PVBF were measured under basal conditions, two hours after propranolol ingestion or placebo, then one and two hours after molsidomine or placebo ingestion. TAV and PVBF remained unchanged in patients treated with placebo. Molsidomine reduced TAV by 23.8 +/- 19.5% in group 1 (P < 0.01) and by 25.6 +/- 21.4% in group 2 (P < 0.01). In group 3, a 10% decrease was observed after propranolol (NS). When molsidomine was added, TAV was further decreased (-17.6 +/- 13.3% vs baseline, P < 0.01). PVBF remained unchanged in the three groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Beta-adrenergic-antagonist drugs in the prevention of gastrointestinal bleeding in patients with cirrhosis and esophageal varices. An analysis of data and prognostic factors in 589 patients from four randomized clinical trials. Franco-Italian Multicenter Study Group.

BACKGROUND: The value of beta-adrenergic-antagonist drug therapy for the prevention of initial episodes of gastrointestinal bleeding in patients with cirrhosis and esophageal varices is uncertain, both positive and negative study results having been reported. METHODS: In this study, we analyzed data on individual patients from four randomized, controlled trials to assess the efficacy of this treatment. Of the 589 patients studied, 286 received a beta-adrenergic-antagonist drug (propranolol in 203 and nadolol in 83) and 303 received placebo. RESULTS: After two years, the mean (+/- SE) percentage of patients who had had no upper gastrointestinal bleeding was 78 +/- 3 percent in the beta-adrenergic-antagonist treatment group and 65 +/- 3 percent in the control group (P = 0.002). The percentage of patients without fatal bleeding was 90 +/- 2 percent in the treatment group and 82 +/- 3 percent in the control group (P = 0.01). The percentage of patients surviving after two years was 71 +/- 3 percent in the treatment group and 68 +/- 3 percent in the control group (P = 0.34). After age and severity of cirrhosis were taken into account, the survival rate was better in the treatment group (P = 0.09). The percentage of surviving patients who had had no bleeding after two years was 62 +/- 3 percent in the treatment group and 53 +/- 3 percent in the control group (P = 0.04). Both propranolol and nadolol prevented a first episode of bleeding. Severe cirrhosis and especially the presence of ascites were associated with bleeding (P less than 0.001) and death (P less than 0.001) in both groups. The efficacy of beta-adrenergic-antagonist therapy in the prevention of bleeding (P less than 0.001) and of fatal bleeding (P = 0.004) and in the prevention of bleeding or death (P = 0.005) was the same after adjustment for cause and severity of cirrhosis, ascites, and size of varices. CONCLUSIONS: Propranolol and nadolol are effective in preventing first bleeding and reducing the mortality rate associated with gastrointestinal bleeding in patients with cirrhosis, regardless of severity.

Adrenergic beta-Antagonists↗
PubMed1991

Systemic and splanchnic hemodynamic effects of molsidomine in rats with carbon tetrachloride-induced cirrhosis.

Molsidomine, a long-acting vasodilator mainly used as an antianginal agent, was reported to decrease the portohepatic venous pressure gradient in patients with alcoholic cirrhosis. This study investigated the effects of linsidomine, the active metabolite of molsidomine, on systemic and splanchnic hemodynamics in rats with CCl4-induced cirrhosis using the microsphere technique. Compared with placebo-treated rats, linsidomine-treated animals were found to have a significant decrease in portal venous pressure (-18%, p less than 0.01) and in mean arterial pressure (-16%, p less than 0.01), smaller peripheral resistances (p less than 0.01), greater portal venous inflow (p less than 0.05), smaller splanchnic arteriolar resistances (p less than 0.01) and smaller protocol-lateral resistances (p less than 0.05). Cardiac output, hepatic arterial blood flow, portal blood flow and estimated hepatic blood flow were not significantly different between the two groups of animals. Linsidomine-treated rats exhibited a trend toward greater collateral blood flow compared with controls, but this difference was not significant. We conclude that linsidomine decreases portal venous pressure by reducing portocollateral resistances without affecting liver blood flow. These effects should be beneficial for patients with cirrhosis and portal hypertension.

Animals↗
PubMed1990

[Non-surgical treatment of hemorrhage caused by portal hypertension in cirrhosis: hemostatic treatment, prevention of the first hemorrhage, prevention of recurrence].

Oesophageal varices are found in two-thirds of cirrhotic patients, and they bleed by rupture in only 50% of the cases. Each bleeding episode carries a mortality risk of about 30%. Recurrences occur in 70% of survivors. Patients with cirrhosis may be considered as being at risk of haemorrhage when large varices, notably with "red signs", are discovered at endoscopy. In two-thirds of the cases, the hemorrhage from ruptured oesophageal varices has stopped by the time emergency endoscopy is performed, but its severity mainly depends on its early recurrence. Haemostatic treatments are justified only in the presence of an active haemorrhage. The best method seems to be endoscopic variceal sclerotherapy carried out in a specialized centre by a centre by a trained endoscopist. The other methods should be used only when sclerotherapy has failed. The prevention of recurrences (secondary prophylaxis) mainly rests on the eradication of varices by endoscopic sclerosis. The addition of propranolol to treatment is probably useful. The seriousness of haemorrhages due to rupture of oesophageal varices justifies primary prophylaxis in patients with large varices found at endoscopy. At present, nonselective beta-blockers constitute the best method of primary prophylaxis. In about 1 out of 5 cases, haemorrhages in cirrhotic patients are due to a different lesion, such as ruptured gastric varices or gastric disease due to portal hypertension. The treatment of haemorrhages causes by these lesions has not been clearly defined, but surgical haemostasis is sometimes indicated in case of ruptures gastric varices.

Esophageal and Gastric Varices↗