The effect of enprostil on duodeno-jejunal motility in man.

Motor changes could be involved in the pathogenesis of diarrhoea that complicates the treatment of ulcer disease by prostaglandins. Our aim was to assess the effect of enprostil, a synthetic analogue of PGE2, on duodeno-jejunal motility. During this randomized double-blind crossover study, two manometric recordings, each lasting 20 h (12.00-08.00 hours), were carried out during dosing with 35 micrograms enprostil b.d. or placebo (eight volunteers: part 1), or during dosing with 35 or 70 micrograms enprostil b.d. (nine volunteers: part 2). Subjects were only allowed a standard dinner at 18.00 hours. During fasting, in part 1, the number of phase 3 activity patterns (PIIIs) was higher with enprostil than with placebo (P less than 0.01), without any difference in their characteristics; the overall duration of phase 1 activity was longer with enprostil than with placebo (P less than 0.01). In part 2, during fasting the number and characteristics of the PIIIs were not different, but there was a dose-related increase in PI, and decrease in PII activity. Fed motor patterns did not differ between the two doses of enprostil.

Percutaneous ethanol injection vs. resection in patients with small single hepatocellular carcinoma: a retrospective case-control study with cost analysis.

BACKGROUND: Percutaneous ethanol injection and hepatic resection are the most widely used curative therapeutic options for patients with compensated liver disease and small hepatocellular carcinoma. AIM: To compare percutaneous ethanol injection and hepatic resection in a selected group of consecutive French patients with a single hepatocellular carcinoma, smaller than or equal to 50 mm, in terms of survival, recurrence rate of malignancy and direct costs. METHODS: The analysis of two contemporary cohorts of Child-Pugh A or B patients with a single hepatocellular carcinoma of < or = 50 mm treated by percutaneous ethanol injection (n=55) or hepatic resection (n=50). RESULTS: Long-term survival was not significantly different between the two groups when the size of hepatocellular carcinoma was less than 30 mm. However, the survival of patients with hepatocellular carcinoma larger than 30 mm was higher after hepatic resection than after percutaneous ethanol injection (P=0.044). The cumulative direct costs were significantly higher in patients treated by hepatic resection than in those treated by percutaneous ethanol injection regardless of the tumour size. The calculated costs per month of survival in patients treated with percutaneous ethanol injection and hepatic resection were 999 vs. 3865 euros, respectively (P < 0.001). CONCLUSIONS: Percutaneous ethanol injection is more cost effective than hepatic resection in patients with a single hepatocellular carcinoma smaller than 30 mm. However, in patients with a larger tumour, long-term survival is higher after hepatic resection.

[Ischemic colitic in the elderly: predictive factors of gangrenous outcome]. / Colite ischémique du sujet âgé: facteurs prédictifs de l'évolution gangreneuse.

OBJECTIVE: To better characterize the presentation of gangrenous and non-gangrenous ischemic colitis in subjects older than 60 years, and to identify risk factors of gangrenous outcome. METHODS: Retrospective analysis of 80 cases of ischemic colitis (22 male, 58 female; mean age 76.9 +/- 8.7 years) with 64 and 16 non gangrenous and gangrenous forms, respectively. RESULTS: Hematochezia and diarrhea were significantly less prevalent in gangrenous colitis compared to the non-gangrenous group (31.2% vs 81.2%, P < 0.0001 and 6.2% vs 53.1%, P < 0.0001, respectively), whereas nausea and vomiting, and hyperleukcocytosis were significantly more frequent in the former group (50.0% vs 18.7%, P < 0.01 and 93.7% vs 62.5%, P < 0.02 respectively). Hypertension (P < 0.03), angina (P < 0.05), history of cancer (P < 0.03) and age older than 90 (P < 0.002) were risk factors for gangrenous outcome. After multivariate analysis, only two independent factors were identified, i.e.: hypertension and history of cancer. These factors predicted gangrenous course in 85% of cases. CONCLUSION: Patients older than 60 years suffering from ischemic colitis are at high risk of gangrenous course if they have hypertension or history of cancer.

[The symptom index: progress in the analysis of esophageal pH metry]. / Le marqueur d'événements: un progrès dans l'interprétation de la pH-métrie oesophagienne.

Commercially available pH-monitoring systems include one or more event markers which should allow correlation between reflux episodes and symptoms. However, the clinical relevance of this feature has not yet been thoroughly investigated. In this prospective study, we attempted to establish whether the use of an event marker could improve the accuracy of intraesophageal pH-monitoring and if a correlation between symptoms, as detected by event markers and esophageal exposure to acid could be shown. One hundred seven patients were studied. Only 47 p. 100 used the event marker during 24 h pH-metry. There was no statistical significance in the incidence of gastroesophageal reflux (GER i.e. time spent below pH 4 greater than 4.2 p. 100), age and socioeconomic status between patients who used the marker and those who did not. A concordance index was calculated by dividing the number of reflux episodes associated with a marked event by the total number of marked events. In 50 p. 100 of the 16 patients who used the marker and had GER, the concordance index was greater than 75 p. 100. On the contrary, only 4 out of 35 patients without GER had a concordance index greater than 75 p. 100 (p less than 0.003). Finally, the index was less than 25 p. 100 in 4 patients with GER and in 22 without GER (p less than 0.02). The lowest pH reached within the esophagus was virtually identical during all the reflux episodes, regardless of marker pressing.(ABSTRACT TRUNCATED AT 250 WORDS)

[Multicenter prospective study of prognostic factors of gastroduodenal ulcer hemorrhages. Reevaluation of clinical and endoscopic factors in the era of endoscopic hemostasis]. / Etude prospective multicentrique des facteurs pronostiques des hémorragies ulcéreuses gastroduodénales. Réévaluation des facteurs cliniques et endoscopiques à l'ère de l'hémostase endoscopique.

AIM: To evaluate in a prospective study the prognostic factors of recurrent bleeding and mortality in patients presenting with high risk peptic ulcer bleeding routinely treated by endoscopic hemostasis. PATIENTS AND METHODS: A multicenter study was carried out in 8 Western French hospitals in 144 patients with gastrointestinal bleeding peptic from ulcer type I or IIa, b as defined by Forrest classification. Thirty four and 38 parameters were studied respectively in order to predict recurrent bleeding and death. Significant predictive factors (P < 0.1) in univariate analysis were entered in a multivariate logistic regression analysis. RESULTS: Endoscopic hemostasis was performed in 108 of 144 cases (75%). Recurrent bleeding and death occurred in 39 (28%) and 22 cases (15%), respectively. By multivariate analysis, the only predictor of rebleeding was hypovolemia at admission. Predictors of death were ASA score, cardiovascular Goldman score and recurrent bleeding. In this study, prevalence of Helicobacter pylori infection was low (41%) but was not a predictive factor. CONCLUSIONS: In a selected population of peptic ulcer bleeding patients with high risk of rebleeding, prevalence of recurrent bleeding and death remains rather high, despite routine endoscopic hemostasis. In the era of endoscopic hemostasis, clinical parameters remain the best prognostic factors of peptic ulcer bleeding outcome.

[Meckel's diverticulum Diagnosed by CT-Enteroclysis]. / Diagnostic d'un diverticule de Meckel hémorragique par entéroscanner.

The authors report the case of a 24 year old woman presenting with acute lower GI hemorrhage caused by a Meckel's diverticulum. Diagnosis was made by CT-enteroclysis and confirmed at surgery. This new imaging technique will be briefly described and compared to the other more traditional small bowel imaging techniques. The authors will then present the CT-enteroclysis imaging features of this congenital anomaly.

Isosorbide mononitrate and propranolol compared with propranolol alone for the prevention of variceal rebleeding.

The aim of this study was to test the effectiveness of isosorbide-5-mononitrate (IM) as an adjunct to propranolol (PR) in the prevention of variceal rebleeding. Ninety-five cirrhotic patients with variceal bleeding were randomly assigned to treatment with PR + IM (46 patients) or PR alone (49 patients). Eighteen patients in the PR + IM group and 28 in the PR group had rebleeding during the 2 years after randomization. The actuarial probability of rebleeding 2 years after randomization was lower in the PR + IM group (40.4% vs. 57.4%) but the difference was not significant (P =. 09). However, the decrease in the risk of rebleeding reached statistical significance after stratification according to age, i.e. less than 50 versus >/=50 years old, (P =.03) or by adding an additional year of follow-up (P =.05). No significant difference was found in rebleeding index and survival. The multivariate Cox analysis indicated first, that both treatment (P =.03) and age (P =. 001) were factors predictive of rebleeding and second, that PR + MI reduced the risk of rebleeding by half (relative risk: 0.51, 95% confidence interval: 0.28-0.95). Seven patients in the PR + MI group and 1 patient in the PR group had to discontinue one of the drugs because of adverse events (P =.03). These results suggest that the addition of IM improves the efficacy of PR alone in the prevention of variceal rebleeding in cirrhotic patients. However no beneficial effects were observed on other parameters reflecting the efficacy of treatment.

Short-chain fatty acids do not alter jejunal motility in man.

Short-chain fatty acids (SCFAs) alter ileal and colonic motility, but their effects on duodenojejunal motility are unknown. Simultaneous jejunal manometric recordings and hydrogen breath tests after lactulose were performed in eight healthy subjects during continuous duodenal infusion of either saline or SCFAs. These experiments were conducted in the fasting state and postprandially. The effects of various boluses of SCFAs on duodenojejunal motility were also determined in six subjects. During the fasting period, the number and characteristics of migrating motor complex, prolonged propagated contractions, discrete clustered contractions, motility index, and orocecal transit time were similar during saline and SCFAs. Similarly, the motility index and the duration of the postprandial period were not different between SCFAs and saline after the meal. The motility index was significantly increased after each of the 100-ml boluses (saline or SCFAs), but was not altered after the 12.5-ml boluses, suggesting a volume-related effect. Thus, SCFAs do not seem to affect proximal small bowel motility in healthy humans.

Single-dose pharmacokinetics of amprenavir, a human immunodeficiency virus type 1 protease inhibitor, in subjects with normal or impaired hepatic function.

Amprenavir (141W94) is extensively metabolized by P450 cytochromes, specifically, CYP3A4. Because hepatic insufficiency reduces P450-mediated metabolism, the concentrations in plasma of drugs metabolized through this pathway are often increased in subjects with liver disease. Following administration of a single, oral dose of 600 mg of amprenavir, pharmacokinetic parameters were determined for 10 subjects with severe cirrhosis, 10 subjects with moderate cirrhosis, and 10 healthy volunteers. Model-independent methods for determining the area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC(0-infinity)) showed an increase in amprenavir AUC(0-infinity) of 2.5-fold in the group with moderate cirrhosis and 4.5-fold in the group with severe cirrhosis compared with that in the control group of healthy volunteers (P < 0.05). AUC(0-infinity) was linearly related to the severity of liver disease, as assessed by the Child-Pugh score. Of the laboratory data used to calculate the Child-Pugh score, only the mean total bilirubin concentration showed a significant relationship with AUC(0-infinity). The relationship between the total bilirubin concentration and the AUC(0-infinity) of amprenavir was well characterized by a simple E(max) model, suggesting that the total bilirubin concentration may be a useful parameter for predicting the amprenavir AUC in subjects with hepatic insufficiency. Finally, the sera of cirrhotic subjects showed significant decreases in the levels of alpha(1)-acid glycoprotein, the primary plasma binding protein for amprenavir. On the basis of the results of this study, for an exposure equivalent to a clinical dose of 1,200 mg twice daily in subjects without cirrhosis, subjects with Child-Pugh scores of 5 to 8 should receive a twice-daily 450-mg dose of amprenavir, and subjects with Child-Pugh scores of 9 to 15 should receive a twice-daily 300-mg dose of amprenavir.

Does elective sclerotherapy improve the efficacy of long-term propranolol for prevention of recurrent bleeding in patients with severe cirrhosis? A prospective multicenter, randomized trial.

We conducted a prospective, multicenter, randomized trial to compare the efficacy of sclerotherapy plus propranolol with that of propranolol alone in the prevention of recurrent gastroesophageal bleeding in severely cirrhotic patients. For 2 yr (1987 to 1988) 131 patients (96% of whom were alcoholic) with Child-Pugh class B or C cirrhosis (56% were class B and 44% were class C) were randomly assigned to one of our two treatment groups after cessation of variceal bleeding, without hemostatic sclerosis, and were observed for at least 2 yr. Treatment observance was good in 89% of cases; alcohol withdrawal was observed in 62% of cases. Sclerotherapy was performed weekly with 1% polidocanol, and variceal obliteration was obtained in 83% of cases, in a mean number of four sessions. The cumulative percentages (expressed as mean +/- S.D.) of recurrent bleeding at 2 yr were 42% +/- 6% for propranolol plus sclerotherapy and 59% +/- 6% for propranolol alone (a nonsignificant difference). Twenty-eight patients from the propranolol group but only 12 patients from the propranolol-plus-sclerotherapy group had recurrent bleeding from esophageal variceal rupture (p less than 0.01). The total number of blood units per patient with recurrent bleeding was slightly but not significantly more important in the propranolol group (8 +/- 7) than in the propranolol-plus-sclerotherapy group (5 +/- 5; p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Early administration of vapreotide for variceal bleeding in patients with cirrhosis.

BACKGROUND: In patients with cirrhosis, pharmacologic or endoscopic treatment may control variceal bleeding. However, the effects of early administration of a somatostatin analogue followed by endoscopic treatment are unknown. METHODS: We studied the effects of treatment with vapreotide, a somatostatin analogue, begun before endoscopic treatment in 227 patients with cirrhosis who were hospitalized for acute upper gastrointestinal bleeding. The patients were randomly assigned to receive vapreotide (a 50-microg intravenous bolus followed by an infusion at a rate of 50 microg per hour for five days) or placebo within a mean (+/-SD) of 2.3+/-1.5 hours after admission. All the patients received endoscopic treatment a mean of 2.6+/-3.3 hours after the infusion was begun. After the exclusion of 31 patients whose bleeding was not caused by portal hypertension, there were 98 patients in each group. RESULTS: At the time of endoscopy, active bleeding was evident in 28 of 91 patients in the vapreotide group (31 percent), as compared with 43 of 93 patients in the placebo group (46 percent) (P=0.03). During the five-day infusion, the primary objective--survival and control of bleeding--was achieved in 65 of 98 patients in the vapreotide group (66 percent) as compared with 49 of 98 patients in the placebo group (50 percent) (P=0.02). The patients in the vapreotide group received significantly fewer blood transfusions (2.0+/-2.2 vs. 2.8+/-2.8 units, P=0.04). Overall mortality rates at 42 days were not significantly different in the two groups. CONCLUSIONS: In patients with cirrhosis and variceal bleeding, the combination of vapreotide and endoscopic treatment is more effective than endoscopic treatment alone as a method of controlling acute bleeding. However, the use of combination therapy does not affect mortality rates at 42 days.