PubMed Health⌕ Search

Biomedical subjects

G Pomier-Layrargues

Publications and source records attributed to G Pomier-Layrargues.

At least 55 records · Page 3Linked to original sources
PubMed1992

Transjugular intrahepatic portacaval stent shunt as a rescue treatment for life-threatening variceal bleeding in a cirrhotic patient with severe liver failure.

Variceal bleeding in cirrhotic patients with severe liver failure that is not controllable by endoscopic sclerotherapy is a life-threatening situation. We report the case of a patient with decompensated cirrhosis (Pugh class C) who bled repeatedly from gastric varices despite multiple sessions of sclerotherapy. The portal vein was catheterized by a transjugular approach. A tract between a hepatic vein and the portal vein was created after balloon dilatation, and this opening was stented with an expandable stainless steel Palmaz stent. The portal vein pressure decreased from 35 mm Hg to 19 mm Hg after shunting. Gastric varices also were embolized. Two months later, bleeding had not recurred; the shunt remained opened and the marked decrease in portal pressure still persisted. Endoscopy showed the disappearance of gastric varices. This procedures could become a life-saving therapeutic option for such critically ill cirrhotic patients.

Catheterization↗
PubMed1989

Pharmacokinetics of benzodiazepine antagonist Ro 15-1788 in cirrhotic patients with moderate or severe liver dysfunction.

Ro 15-1788, a benzodiazepine antagonist, has been advocated as a new treatment for hepatic encephalopathy. This drug is extensively metabolized by the liver in normal subjects. In the present study, we examined Ro 15-1788 disposition in eight healthy controls (Group I), eight cirrhotic patients with moderately impaired liver function (Pugh score less than 10, Group II) and eight patients with severe liver dysfunction (Pugh score greater than 10, Group III). The subjects of each group were age and sex matched. After an intravenous infusion of 2 mg Ro 15-1788 over 5 min, blood samples were taken at fixed intervals up to 7 hr after the infusion. Plasma levels of the drug were determined by capillary gas chromatography. In controls, Ro 15-1788 had a high plasma clearance [16.3 +/- 2.6 ml per min per kg (mean +/- S.D.)], a short half-life (45.7 +/- 8.5 min), a large volume of distribution (0.62 +/- 0.09 liter per kg) and a low plasma protein binding (45 +/- 6%). Plasma clearance was reduced markedly in both groups of cirrhotic patients (-57 and -74%, respectively); the volume of distribution was unchanged in Group II and moderately increased in Group III (+37%). The elimination half-life was markedly prolonged in Groups II and III (+66 and +210%, respectively). Plasma clearance and Pugh score were highly correlated in cirrhotic patients (r = 0.830, p less than 0.001). The plasma protein binding of Ro 15-1788 was lower in cirrhotics, resulting in a significant increase in the free fraction of the drug (+16% in Group II; +44% in Group III).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Drug disposition in patients with HBsAg-positive chronic liver disease.

Chronic infection with hepatitis B virus (HBV) results in a spectrum of hepatic abnormalities ranging from minimal liver dysfunction to severe liver failure. These patients provide an opportunity to examine the relationship between the evolution of the liver disease and the ability to metabolize drugs. We have examined hepatic drug disposition in patients with chronic persistent hepatitis, chronic active hepatitis, and cirrhosis due to HBV infection. Four model drugs were used: two low-extraction capacity-limited drugs (antipyrine and aminopyrine) and two high-extraction flow-limited drugs (ICG and lidocaine). The disposition of the four drugs tested was comparable to that of healthy controls in patients with chronic persistent hepatitis, chronic active hepatitis, and mild cirrhosis. In patients with severe cirrhosis (as defined by the presence of ascites, encephalopathy, or large esophageal varices), there was a significant impairment in the aminopyrine breath test (-31%) and in the clearance of antipyrine (-53%), lidocaine (-49%), and ICG (-54%). These results indicate that impairment of drug clearance occurs only late in the evolution of HBV-related chronic liver disease. This is in keeping with the known slow and insidious progression of the disease.

Adult↗
PubMed1987

Systemic and hepatic hemodynamics after variceal hemorrhage: effects of propranolol and placebo.

Hepatic and systemic hemodynamics were measured in 19 cirrhotic patients with variceal bleeding enrolled in a controlled trial of propranolol for the prevention of rebleeding. The patients were studied on three separate occasions. The first study was performed before randomization within 24 h of the bleeding episode, once hemodynamic stabilization had been achieved. The second study was performed after 10 days of treatment, and the third after 6 mo without rebleeding. Propranolol dosage was titrated according to blood levels. Wedged and free hepatic venous pressures and the hepatic venous pressure gradient were recorded. Hepatic blood flow and cardiac output were also measured. Before treatment, the groups of patients treated with propranolol (n = 11) or placebo (n = 8) were comparable according to clinical, biochemical, and hemodynamic parameters. After 10 days, hepatic venous pressure gradient decreased similarly in the two groups (-20% in the propranolol group, -25% in the placebo group). Cardiac output fell only in the propranolol group (-40%). Hepatic blood flow remained unchanged in either group. After 6 mo, hepatic venous pressure gradient remained lower than the values from the first (within 24 h of bleeding) study in both the propranolol group (n = 5) and the placebo group (n = 6). Our results suggest that portal pressure increases shortly after hemorrhage with a return to baseline values 10 days later, and that propranolol does not further magnify these changes. Spontaneous changes in hepatic hemodynamics after variceal hemorrhage must be taken into account when evaluating the effect of pharmacologic agents on portal pressure.

Adult↗
PubMed1987

Emergency portacaval shunt for variceal hemorrhage. A prospective study.

Emergency portacaval shunt for variceal bleeding is associated with a high operative mortality, particularly if used as a last resort. Because of this, a strong case has been made against emergency shunt. This report describes an experience with emergency portacaval shunt for the treatment of variceal bleeding when used systematically after hemodynamic stabilization and control of the bleeding episode with balloon tamponade, if necessary, in patients with mild or moderate liver disease. The population studied comprised 62 consecutive patients who rebled from varices while participating in a controlled trial of propranolol for the prevention of rebleeding. Of the 62 patients, nine died of massive hemorrhage and 53 survived the hemorrhage. Of the 53 survivors, 11 had severe liver disease and were not considered for shunt surgery. Of the remaining 42 patients with mild or moderate liver disease, 36 had emergency central portacaval shunt. The interval between endoscopic diagnosis of variceal bleeding and surgery averaged 19 +/- 3 hours (mean +/- SE). The operative mortality rate, defined as in-hospital mortality, was 19%. One- and 2-year survival rates were 78% and 71%, respectively. The incidence of postoperative hepatic encephalopathy was 36%; all patients responded favorably to protein restriction and lactulose. Thus, under specific conditions, emergency portacaval shunt results in an acceptable long-term survival rate. In patients with mild or moderate liver disease, emergency portacaval shunt should be considered when other forms of treatment for the prevention of variceal rebleeding have failed.

Emergencies↗
PubMed1986

Effect of portacaval shunt on drug disposition in patients with cirrhosis.

To examine the consequences of liver blood flow variations on drug disposition in cirrhosis, we studied the effects of portacaval shunt on drug clearance in 35 cirrhotic patients. Lidocaine clearance and bioavailability, indocyanine green (ICG) clearance, aminopyrine breath test, and hepatic blood flow were measured before and 18 months after surgery. The patients were divided into two groups according to severity of disease: 14 patients (group 1) had slight liver dysfunction (ICG extraction ratio greater than 0.25) and 21 patients (group 2) had severe liver disease (ICG extraction ratio less than 0.25). After portacaval shunt the decrease in hepatic blood flow was similar for both groups (-65%). In group 1, ICG systemic clearance decreased from 9.10 +/- 0.68 to 4.40 +/- 0.34 ml/min . kg (p less than 0.05), whereas ICG intrinsic clearance remained unchanged; lidocaine systemic clearance decreased from 7.93 +/- 0.93 to 5.09 +/- 0.33 ml/min . kg (p less than 0.05), whereas lidocaine intrinsic clearance remained unchanged; bioavailability increased from 0.601 +/- 0.076 to 1, resulting in an abrupt reduction of oral clearance from 18.01 +/- 4.90 to 5.09 +/- 0.33 ml/min . kg (p less than 0.05). In group 2, ICG systemic clearance decreased slightly from 3.90 +/- 0.39 to 2.28 +/- 0.16 ml/min . kg (p less than 0.01) and ICG intrinsic clearance was not modified; lidocaine systemic and intrinsic clearance remained unchanged; and bioavailability increased from 0.779 +/- 0.229 to 1, resulting in a decrease of oral clearance from 7.68 +/- 1.65 to 4.23 +/- 0.37 ml/min X kg (p less than 0.05). The aminopyrine breath test was not affected by surgery in either group. We conclude that reduction of hepatic blood flow after portacaval shunt has only minimal effects on drug disposition in patients with severe liver disease, but results in a notable reduction in the clearance of high-extraction drugs in cirrhotics with mild liver disease.

Adult↗
PubMed1986

Intrahepatic circulation in liver disease.

Using the multiple indicator dilution approach, events occurring in the microvascular bed can be characterized in experimental animals with different types of cirrhosis and in man. Intrahepatic shunts can be found shunting blood away from sinusoids in both cirrhotic patients and cirrhotic animals. Such shunts were present in about one-third of cirrhotic patients with portal hypertension, and occurred mainly between the portal vein and hepatic veins. In cirrhotics, portohepatic anastomoses are usually large in diameter (more than 20 micron in diameter). Collagenization of the space of Disse and the progressive transformation of sinusoids into capillary-like channels decrease the extravascular space accessible to albumin and probably to other large molecules and protein-bound substances. However, unlike findings obtained in well-capillarized organs, these sinusoidal changes do not appear to limit the diffusion of sucrose, water, and lipophilic substances, such as lidocaine in the extravascular and intracellular spaces. The pattern observed for labeled sucrose curves following hepatic artery injection in cirrhotic patients could be secondary to the passage through the dense peribiliary capillary plexus originating from the enlarged arterial bed in cirrhosis. The difference in the perfusion of cirrhotic nodules with regard to the portal venous and hepatic artery routes introduces important new concepts in the overall mechanism of the elimination of endogenous and exogenous substances by the cirrhotic liver: blood entering the liver by the two afferent vessels will not flow through the same vascular bed before reaching the efferent hepatic veins.

Animals↗
PubMed1985

Treatment of acute hepatic encephalopathy in cirrhotics with a branched-chain amino acids enriched versus a conventional amino acids mixture. A controlled study of 70 patients.

Acute hepatic encephalopathy in 70 cirrhotic patients was monitored during parenteral administration of amino acids between January 1979 and January 1984. The diagnosis of cirrhosis was confirmed by needle biopsy, and HE by conventional clinical and EEG parameters. The infusion of AA solutions was initiated 48 h after admission and during a 5-day period: 34 patients received a control aminoacid solution, a commercially available AA mixture (Azonutril), and 36 patients a modified solution enriched in BAA prepared from crystallized AA dissolved in distilled water. The calorie intake for both groups was 1600 calories per day from glucose and lipid emulsion. No significant difference was noted based on clinical evolution, even though the plasma AAA/BAA ratio was corrected using the modified AA solution. Of the 34 patients in Group 1: 10 improved, 14 were unchanged, 10 deteriorated and 7 died. Of the 36 patients in Group 2: 12 improved, 14 were unchanged, 10 deteriorated and 7 died. EEG tracing evolved in parallel fashion. The authors conclude that modified AA solutions are ineffective in the treatment of acute hepatic encephalopathy in cirrhotic patients.

Acute Disease↗
PubMed1985

Hepatic circulation in cirrhosis.

Using the multiple indicator dilution approach, events occurring in the microvascular bed can be characterized and are compatible with the two kinds of anatomical alterations in cirrhotic livers: capillarization and intrahepatic shunts. The combination of these two kinds of alteration contributes to the progressive limitation of the blood-liver exchange. The decreased ability of the liver to clear endogenous and exogenous substrates in cirrhosis is generally thought to result from a reduction of liver cell mass and/or function. Our data suggest that abnormalities in the hepatic uptake of these substrates may also contribute to the impaired liver function in cirrhosis. Capillarization of the hepatic sinusoid is of particular importance in the overall process of elimination while intrahepatic shunts, when present, further exacerbate the functional effects of capillarization.

Capillaries↗
PubMed1985

[Sclerosing cholangitis following surgical treatment of hydatid cysts of the liver. Probable role of the formol injection of bile ducts].

Three cases of secondary sclerosing cholangitis which developed during the early postoperative phase of surgical treatment of hydatid liver cysts are reported. The cysts had ruptured into the biliary tree and the treatment consisted of infection of formol into the cysts. Evolution was pejorative since one patient died within 3 months and the remaining two underwent liver transplantation following biliary sclerosis. An experimental protocol using dogs has shown that the injection of 5, 10 and 20 p. 100 formalin into normal bile ducts rapidly causes sclerosing cholangitis which often leads to death. In man, it is very likely that the contact of 2 p. 100 formalin with mucosal tissue damaged by episodes of cholangitis could result in sclerosing cholangitis. These observations should be sufficient to discourage the use of formalin to sterilize hydatid cysts of the liver.

Adolescent↗
PubMed1983

[Transparietal biliary drainage. 27 cases].

During a 2-year period, 27 patients with obstructive jaundice (due to cancer in 27) underwent transhepatic biliary drainage with an 85% success rate. Most of the failures occurred in early attempts and were due to lack of experience. In neoplastic obstructive jaundice, endoprosthesis proved superior to external drainage: jaundice regressed more frequently and more completely, the patients' comfort was improved, survival was significantly prolonged and complications were less frequent. Per-operative biliary drainage, used in a controlled trial, proved useless, as patients developed cholangitis.

Adult↗
PubMed1983

[Pharmacokinetics and metabolism of acetaminophen in normal, alcoholic and cirrhotic subjects].

It is well known that a chemically reactive metabolite of acetaminophen formed in the liver can cause hepatic necrosis. The amount of cysteine and N-acetylcysteine derivatives excreted in the urine is an index of the amount of reactive metabolite produced. We have examined the pharmacokinetics and the pattern of acetaminophen metabolites in the urine, in 6 healthy controls, in 9 alcoholic subjects without liver disease, and in 11 patients with alcoholic cirrhosis but abstaining from alcohol. In alcoholics, oral clearance of the drug was similar to that of control subjects, but the amount of cysteine and N-acetylcysteine conjugates excreted in urine was significantly increased. In cirrhotics, the clearance of acetaminophen was decreased by 50 p. 100, but the pattern of urinary metabolites was unchanged. These results support previous anecdotal reports of increased acetaminophen hepatotoxicity in alcoholic subjects.

Acetaminophen↗
PubMed1982

[Zieve's syndrome and acute alcoholic hepatitis (author's transl)].

Zieve's syndrome, characterized by jaundice, hyperlipaemia and haemolytic anaemia, usually develops in young, chronically alcoholic subjects with enlarged fatty liver. Hitherto, the course of the disease was considered favourable in most patients, with complete regression of clinical, biological and anatomical symptoms. However, the discovery of acute alcoholic hepatitis during repeat needle-biopsy of the liver confirms that in some cases steatosis may mask hyaline necrosis and neutrophil infiltration. Zieve's syndrome therefore is not benign but precedes acute alcoholic hepatitis episodes on a normal, fibrotic or cirrhotic liver.

Acute Disease↗
PubMed1981

Blood-brain transport of tryptophan and phenylalanine: effect of portacaval shunt in dogs.

The blood-brain uptake process for tryptophan and phenylalanine was investigated using the multiple-indicator dilution technique in 13 unanesthetized dogs with and without portacaval shunts. Tracer doses of labeled albumin (extracellular reference) and tryptophan or phenylalanine, prepared in autologous dog plasma, were injected into one carotid artery, and dorsal sagittal sinus dilution curves were obtained. Portacaval shunting was not associated with significant changes in the initial brain uptake ratio U for tryptophan or phenylalanine, despite increases in plasma phenylalanine and tyrosine. In the 13 dogs, U was not significantly correlated with the plasma levels of either the different branched-chain or aromatic amino acids or the molar ratio between these groups. These findings do not support the current hypothesis that the active transport of aromatic amino acids across the blood-brain barrier is increased after portacaval shunt. Our data suggest, instead, that the blood-brain uptake process for aromatic amino acids is linear and increases in shunted animals because their plasma levels are increased.

Animals↗