[Oral cimetidine does not induce hypersecretion of prolactin].
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Biomedical subjects
Publications and source records attributed to G Pomier-Layrargues.
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The authors have observed 5 cases of cholestatic jaundice with cytolysis during treatment with amineptine, a new tricyclic compound recently made available. The responsibility of the drug was virtually certain for the following reasons: (a) there was no other cause of jaundice, such as viral infection, gallstones, toxic agents or association with other hepatotoxic drugs; (b) clinical and biochemical findings were similar in all patients; (c) in 2 patients, reintroduction of the drug after temporary withdrawal resulted in rapid recurrence of the condition, with the same symptoms and course. The shorter delay (2 and 8 days instead of 11 and 18 days) between absorption of amineptine and reappearance of the symptoms in these two patients is suggestive of an immunoallergic mechanism.
The relative importance of portal hypertension and intrahepatic portal-systemic shunting in the pathogenesis of hyperglobulinemia is examined in 31 alcoholic cirrhotic patients and 6 patients with idiopathic portal hypertension. The degree of portal hypertension was evaluated by combined umbilicoportal and hepatic vein catheterization and the intrahepatic portal-systemic hunting was assessed by the Kupffer uptake of [125I]albumin microaggregates during a single passage through the liver. All patients had comparable severe portal hypertension and most had bled from ruptured varices; however, no demonstrable relationship could be found between portal hypertension and hyperglobulinemia. Elevated levels of serum gammaglobulins and immunoglobulins (mainly IgG) were observed only in cirrhotic patients, particularly those with markedly altered Kupffer cell uptake. It is concluded that intrahepatic portal systemic shunting as evaluated by the Kupffer cell uptake is more important than the collateral circulation secondary to portal hypertension in the pathogenesis of hyperglobulinemia in alcoholic cirrhotic patients.
Hepatic encephalopathy (HE) is currently felt to be secondary to a disturbance in the metabolism of cerebral catecholamines with a decline in dopamine and noradrenaline and a rise in the false neurotransmitter octopamine. The aim of this study was to evaluate brain tissue levels of dopamine, noradrenaline, and octopamine in patients with cirrhosis and HE. This study includes 34 patients: 22 were cirrhotic, 12 were control subjects. Among the 22 cirrhotic patients, 19 had HE, three did not. Tissue specimens were obtained at necropsy from the locus niger, caudate nucleus, hypothalamus, thalamus and frontal cortex, and from the frontal cortex during neurosurgical procedures. Our results showed that (1) dopamine and noradrenaline levels are identical in cirrhotic patients with or without HE and in patients without liver disease (P < 0.05); (2) octopamine levels are higher in control subjects than in patients with cirrhosis and HE. In conclusion, there is no decline in dopamine and noradrenaline levels in the brain tissues of cirrhotic patients with HE, and this is in contradication with the animal findings; octopamine levels are not raised. Hepatic encephalopathy in human liver cirrhosis does not seem to be secondary to a disturbance in cerebral catecholamines.
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The diagnosis of proctated jaundice is done in 50% of all cases by clinical examination; in 30% of all cases by peritoneoscopy; in the other 20% instrumental opacification of the biliary tract is required (before the laparotomy) in order to determine the site and the nature of the cholestasis. Among these instrumental devices, a transhepatic cholangiography with the Okuda needle allows biliary tract opacification in 98% of all cases if the obstacle is extra-hepatic and in 69% of all cases if the obstacle is intra-hepatic. This technique is easy to perform, without danger, and readily available to any physician. It should be performed after the peritoneoscopy and before the retrograde cholangiography.
The simultaneous measurement of wedged hepatic vein pressure (WHVP) and portal vein pressure (PVP) was performed in 156 cirrhotic patients. In the 110 alcoholic cirrhotic patients (97 micronodular and 13 macronodular cirrhosis), WHVP and PVP were closely related (25.8 +/- 6.3 vs. 25.9 +/- 6.3 mm Hg; p = not statistically significant). The difference between the two parameters was greater than 4 mm Hg in only six patients. In the 46 patients with nonalcoholic cirrhosis (41 macronodular and 1 micronodular cirrhosis; 4 primary biliary cirrhosis), PVP was significantly higher than was WHVP (25.8 +/- 6.2 vs. 21.7 +/- 6.8 mm Hg; p less than 0.001); in 20 patients, PVP exceeded WHVP by more than 4 mm Hg, and the mean difference was 7.5 mm Hg. There was no correlation between the porto-hepatic gradient and total hepatic blood flow measured by the indocyanine green single injection method or the portal fraction of total hepatic blood flow measured by indicator dilution curves. It is concluded that: (i) measurement of WHVP in alcoholic cirrhosis provides a reliable estimate of the severity of the portal hypertension, and (ii) hemodynamic evaluation of nonalcoholic cirrhosis should include PVP measurement in order to avoid underestimation of the porto-hepatic gradient.
The aminopyrine breath test has been proposed as a quantitative test of hepatic function, but its long-term prognostic value in patients with cirrhosis has not been determined. The aim of this study was to examine the usefulness of the aminopyrine breath test in assessing prognosis and to compare it with traditional methods of evaluating liver function. One-hundred eighty-seven patients with histologically confirmed cirrhosis were studied prospectively. An aminopyrine breath test was obtained at the time of inclusion in the study and results were expressed as per cent of the dose excreted in 2 hr. At inclusion, the severity of liver disease was also assessed according to the Pugh modification of the Child-Turcotte classification based on ascites, neurological status, serum albumin, serum bilirubin and prothrombin time. Mean follow-up was 844 days. During that period, 59 of 187 patients died of their liver disease. Two-year survival decreased with increasing Child-Turcotte classification score: survival was 98% in Child Class A patients (n = 62), 66% in Child Class B (n = 76) and 36% in Child Class C (n = 49) (chi 2 = 65.6, p less than 0.001). Two-year survival also decreased significantly with increasing degree of aminopyrine breath test abnormalities: survival was 90% in patients with aminopyrine breath test greater than 4% (n = 56); 78% in patients with aminopyrine breath test = 2 to 4% (n = 66), and 43% in patients with aminopyrine breath test less than 2% (n = 65) (chi 2 = 36.9, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
We conducted a prospective, randomized single-blind trial of propranolol for the prevention of recurrent variceal bleeding. Seventy-nine patients shown to have variceal hemorrhage at endoscopy were included in the study within 72 hr following diagnosis. Fifty-seven patients had alcoholic cirrhosis, 10 cryptogenic cirrhosis, 6 posthepatitic cirrhosis, 4 biliary cirrhosis, 1 portal vein thrombosis without cirrhosis and 1 idiopathic portal hypertension. The severity of liver disease at inclusion was assessed according to the Pugh modification of the Child-Turcotte classification: 9 (11%) had Class A; 41 (52%) Class B, and 29 (37%) Class C disease. Patients were randomly assigned by sealed envelope to the propranolol group (42 patients) or the placebo group (37 patients). Propranolol dosage was titrated in order to produce plasma concentrations of propranolol of 50 to 150 ng per ml. beta-blockade was also confirmed by isoproterenol testing. The cumulative percentages of patients free of rebleeding 1 and 2 years after inclusion were 31 and 21% in the propranolol group, and 25 and 17% in the placebo group; both differences were not significant. Cumulative 1 and 2 years survival were also comparable: 64 and 54% in the propranolol group vs. 70 and 63% in the placebo group. There was no evidence for a therapeutic effect of propranolol after adjusting for potential confounding variables by multiple logistic regression. We conclude that propranolol is not effective for the prevention of variceal rebleeding, when administered early following the initial bleed, in cirrhotics unselected with respect to the severity of the liver disease.
Previous studies have established the reliability of percutaneous portal venous pressure measurement using a Chiba needle, a procedure requiring fluoroscopic guidance. Intrahepatic pressure has been advocated by some as a simple and safe index of portal venous pressure. The aim of this study was to examine the reliability of intrahepatic pressure measurement and its relationship to portal venous pressure. Fifty patients requiring liver biopsy were included: 29 with cirrhosis (n = 20 micronodular, n = 9 macronodular) and 21 with various hepatic disorders but no cirrhosis. The procedure was performed under fluoroscopic guidance, using a Chiba needle connected to a manometer by a saline-filled catheter. Immediately prior to biopsy, each patient underwent measurement of: (i) 3 to 5 separate intrahepatic pressures, the intraparenchymal site being inferred by the lack of blood or bile return; and (ii) portal and hepatic venous pressures, the intravascular position of the needle being ascertained by the reflux of blood and the vessel identified with injection of contrast. Intrahepatic pressure measurements showed great intraindividual variability (variation coefficient up to 115%). Mean intrahepatic pressure (13.19 +/- 8.32 mm Hg) was similar to portal venous pressure (14.43 +/- 6.10 mm Hg) in the noncirrhotics but significantly lower in the cirrhotics (intrahepatic pressure = 18.34 +/- 8.82 mm Hg, portal venous pressure = 22.52 +/- 9.47 mm Hg; p less than 0.01). The difference between these two parameters exceeded 3 mm Hg in 50% of patients (mean = 9 mm Hg, range = 4 to 19 mm Hg), both in cirrhotics and noncirrhotics.(ABSTRACT TRUNCATED AT 250 WORDS)
It has been suggested, from studies of a rabbit model of fulminant hepatic failure, that hepatic encephalopathy might be related to an increase in brain gamma-aminobutyric acid uptake through a more permeable bloodbrain barrier, leading to an overactivity of brain gamma-aminobutyric acid-mediated inhibitory neurotransmission. Five groups of dogs were studied: normal dogs, dogs with secondary biliary cirrhosis without and with hepatic encephalopathy and portacaval shunted dogs without and with hepatic encephalopathy. Brain gamma-aminobutyric acid and sucrose uptake was investigated using the multiple indicator dilution curve technique in unanesthetized dogs. Tracer doses of 99mTc-labeled albumin (extracellular reference substance), 3H-labeled gamma-aminobutyric acid and 14C-labeled sucrose prepared in autologous dog plasma were injected in one carotid artery, and dorsal sagittal sinus dilution curves were obtained. Uptake was calculated by comparing the areas under the 99mTc-labeled albumin and the [3H]gamma-aminobutyric acid (or [14C]sucrose) curves from appearance to peak height. After killing, brain gamma-aminobutyric acid levels were measured in the frontal cortex by high-performance liquid chromatography and glutamic acid decarboxylase activities using a radioenzymatic assay. Brain gamma-aminobutyric acid postsynaptic receptors were assessed using [3H]muscimol binding studies. There were no significant changes in cirrhotic and shunted dogs with or without hepatic encephalopathy with regard to brain gamma-aminobutyric acid and sucrose uptake, brain gamma-aminobutyric acid levels and glutamic acid decarboxylase activities. [3H]Muscimol binding studies did not show any changes in the number nor in the affinity of postsynaptic gamma-aminobutyric acid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
The integrity of GABA-A receptors and of central benzodiazepine receptors was evaluated in membrane preparations from prefrontal cortex and caudate nuclei obtained at autopsy from nine cirrhotic patients who died in hepatic coma and an equal number of age-matched control subjects. Histopathological studies revealed Alzheimer Type II astrocytosis in all cases in the cirrhotic group; controls were free from neurological, psychiatric or hepatic diseases. Binding to GABA-A receptors was studied using [3H]muscimol as radioligand. The integrity of central benzodiazepine receptors was evaluated using [3H]flunitrazepam and [3H]Ro15-1788. Data from saturation binding assays was analyzed by Scatchard plot. No modifications of either affinities (Kd) or densities (Bmax) of [3H]muscimol of central benzodiazepine binding sites were observed. These findings do not support recent suggestions that alterations of either high-affinity GABA or benzodiazepine receptors play a significant role in the pathogenesis of hepatic encephalopathy.
The objective of this study was to assess the prognostic value of spontaneous portosystemic shunting and liver function for survival and spontaneous hepatic encephalopathy after end-to-side portacaval shunt in cirrhotic patients. One hundred ninety-eight patients with variceal hemorrhage as shown by endoscopy were evaluated. Forty-five were excluded because of uncontrollable hemorrhage; 84 were rejected because they were poor operative risk, had portal vein thrombosis or had been previously treated with beta-blockers, sclerotherapy or surgery. The remaining 69 patients were enrolled in this prospective study. There were 43 patients with alcoholic cirrhosis, 23 with cryptogenic cirrhosis and three with primary biliary cirrhosis. The severity of liver disease was assessed according to the Pugh classification: 37 patients (54%) had Pugh's score 5 to 7, 26 (38%) had 8 to 10 and six (8%) had 11 to 12. Indocyanine green intrinsic clearance was used as a probe of preoperative liver function and lidocaine systemic availability as an index of spontaneous preoperative shunting. All the patients underwent an elective end-to-side portacaval shunt. The length of minimal follow-up was 40 months. One-year survival was 76% and 5-year survival was 46%. During follow-up, 25 patients died from their liver disease and 11 patients died from various causes unrelated to their liver disease. Spontaneous chronic encephalopathy occurred in 16 patients (23%). Age, Pugh's score, active alcoholism, indocyanine green intrinsic clearance and lidocaine systemic availability were tested as prognostic factors in a multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Hepatic encephalopathy is a major complication of portal-systemic shunts with an incidence ranging up to 52%. A small fraction of these patients are refractory to medical therapy. Shunt ligation and colonic procedures are the main surgical approaches. The goal of the latter is to diminish the colonic absorption of nitrogenous substances which are involved in the pathophysiology of hepatic encephalopathy. Six patients, whose average age was 55.7 +/- 2.6 years, were operated for severe postshunt encephalopathy requiring 4.3 +/- 0.9 admissions for a total duration of 76 +/- 26 days over 1-11 years. One patient had undergone a splenoral shunt and 5 had a portacaval shunt. One ligation of the shunt and 5 colon exclusions were performed. The average postoperative hospital stay was 21.5 +/- 3.9 days. The mean follow-up was 47 +/- 20 months. The patient with the shunt ligation remains free of encephalopathy 94 months after the procedure and has not bled from his esophageal varices. Among the 5 colon exclusion patients, there were 1 death and 3 complications. Three patients were completely relieved of their hepatic encephalopathy. One of those 3 died of a subarachnoid hemorrhage 28 months after the surgery. The fourth still needs medication to control a persistent, although improved, encephalopathy that required 2 further hospitalizations. Colon exclusion is a useful intervention in very selected cases. It has a lower operative mortality than total colectomy and the advantage over shunt ligation of not reestablishing hypertension in the portal system.
PURPOSE: To evaluate the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) in the control of bleeding from ectopic varices. METHODS: From 1995 to 2004, 24 cirrhotic patients, bleeding from ectopic varices, mean age 54.5 years (range 15-76 years), were treated by TIPS. The etiology of cirrhosis was alcoholic in 13 patients and nonalcoholic in 11 patients. The location of the varices was duodenal (n = 5), stomal (n = 8), ileocolic (n = 6), anorectal (n = 3), umbilical (n = 1), and peritoneal (n = 1). RESULTS: TIPS controlled the bleeding in all patients and induced a decrease in the portacaval gradient from 19.7 +/- 5.4 to 6.4 +/- 3.1 mmHg. Postoperative complications included self-limited intra-abdominal bleeding (n = 2), self-limited hemobilia (n = 1), acute thrombosis of the shunt (n = 1), and bile leak treated by a covered stent (n = 1). Median follow-up was 592 days (range 28-2482 days). Rebleeding occurred in 6 patients. In 2 cases rebleeding was observed despite a post-TIPS portacaval gradient lower than 12 mmHg and was controlled by variceal embolization; 1 patient underwent surgical portacaval shunt and never rebled; in 3 patients rebleeding was related to TIPS stenosis and treated with shunt dilatation with addition of a new stent. The cumulative rate of rebleeding was 23% and 31% at 1 and 2 years, respectively. One- and 2-year survival rates were 80% and 76%, respectively. CONCLUSION: The present series demonstrates that bleeding from ectopic varices, a challenging clinical problem, can be managed safely by TIPS placement with low rebleeding and good survival rates.
Refractory ascites worsens the end-stage course of decompensated cirrhosis. Transjugular intrahepatic portasystemic shunt (TIPS) has been proposed to treat this condition with erratic success, inducing controversial reports on the risk-benefit ratio associated to this technique. In order to assess the usefulness of TIPS for this indication, this paper updates some definitions concerning the refractory ascites. We also analyze the main complications of TIPS and review some physiopathological pathways, taking peculiar interest in the Montreal experience.