PubMed Health⌕ Search

Biomedical subjects

F Ballet

Publications and source records attributed to F Ballet.

At least 37 records · Page 2Linked to original sources
PubMed1989

Effect of D-tryptophan-6-luteinizing hormone-releasing hormone on the tumoral growth and plasma sex steroid levels in cirrhotic patients with hepatocellular carcinoma.

Certain evidence suggests androgen dependence of hepatocellular carcinoma in cirrhotic patients. Consequently, it was postulated that antiandrogen therapy might be effective in the treatment of hepatocellular carcinoma. D-Tryptophan-6-luteinizing hormone-releasing hormone is a potent agonist analog of luteinizing hormone-releasing hormone which, when chronically administered, inhibits the pituitary gonadal axis and testicular androgen secretion in man. We studied the effects of D-tryptophan-6-luteinizing hormone-releasing hormone on tumoral growth in 17 male cirrhotic patients with hepatocellular carcinoma. After 3 to 6 months of therapy, no tumoral response was observed. Furthermore, measurements of plasma levels of testosterone, dihydrotestosterone, androstenedione, estradiol, estrone and sex hormone-binding globulin were performed before and 3 months after initiation of the antiandrogenic treatment. Before treatment, hypoandrogenism and hyperestrogenism were present; D-tryptophan-6-luteinizing hormone-releasing hormone induced a fall in plasma testosterone and dihydrotestosterone levels. Only a moderate decrease in estradiol and no modification of plasma estrone and sex hormone-binding globulin were found, indicating that the hyperestrogenemia of cirrhotic patients could be attributed to an increase in peripheral aromatization of androgens of adrenal origin. The inability of D-tryptophan-6-luteinizing hormone-releasing hormone to reduce the growth of hepatocellular carcinoma is not totally in disagreement with the concept of androgen dependence of hepatocellular carcinoma since D-tryptophan-6-luteinizing hormone-releasing hormone does not inhibit the production of androgens of adrenal origin.

Aged↗
PubMed1989

Evidence of the intact hepatocyte theory in alcoholic cirrhosis.

To improve our understanding of the predominant operational model involved in the decreased clearance in cirrhosis, hepatic clearance, the extraction ratio of indocyanine green, and liver plasma flow were estimated in cirrhosis, either with a method based on the Fick principle or with a pharmacokinetic method assuming a bicompartmental plasma elimination of the dye. The two methods gave similar values for clearance. In contrast, the pharmacokinetic analysis gave significantly (p less than 0.01) lower hepatic plasma flow values and significantly (p less than 0.01) higher extraction values than those obtained with the reference (Fick principle) method. The main finding of this work is that in these cirrhotic patients, as in normal subjects, 'cellular' extraction estimated by the pharmacokinetic method is in the range of 0.60-0.80, whereas the extraction by the entire liver, assessed by the reference method, is low. In chronic liver diseases such as cirrhosis these data support the predominance of the intact hepatocyte theory, which assumes the existence of intrahepatic shunts associated with normally perfused and normally extracting hepatocytes. In acute liver disease, a cellular damage could be superadded.

Adult↗
PubMed1988

Sex hormone imbalance in male alcoholic cirrhotic patients with and without hepatocellular carcinoma.

To investigate the possible role of sex-hormone imbalance in hepatocellular carcinogenesis in male alcoholic cirrhotic patients, we determined plasma levels of testosterone (T), dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone (DHA), estrone (E1), estradiol (E2), and sex-hormone-binding globulin (SHBG) in 15 men with alcoholic cirrhosis alone and in 15 similar men with alcoholic cirrhosis and hepatocellular carcinoma (HCC). The groups were matched for age and severity of liver disease using Child-Pugh scoring. Patients of both groups had evidence of hypogonadism with a decrease in plasma T levels (P less than 0.02) and of hyperestrogenemia with an increase in E1 (P less than 0.001), E2 (P less than 0.01), and SHBG (P less than 0.01) plasma levels compared with ten healthy age-matched controls. Cirrhotic patients with HCC had significantly lower plasma concentrations of T (P less than 0.02), DHT (P less than 0.01), and DHA (P less than 0.001) than patients with cirrhosis alone. However, the plasma concentrations of A, E1, E2, and SHBG did not significantly differ between these two groups. These results suggest a possible alteration of the estrogen-to-androgen ratio during carcinogenesis of the cirrhotic liver. This is shown by a greater reduction of circulating androgens and a similar elevation of estrogens in the group of cirrhotics with HCC.

Aged↗
PubMed1988

Hepatic transport of bile acids in the isolated perfused rat liver. Structure-kinetic relationship.

We studied the transport kinetics of a series of bile acids from blood to bile in the isolated perfused rat liver in order to define better the relationship between chemical structure of bile acid molecules and efficiency of the overall hepatic transport process. BA studied were taurocholate (TC), glycocholate (GC), cholate (C), tauroursodeoxycholate (TUDC), ursodeoxycholate (UDC) and hyodeoxycholate (HDC). Estimates of intrinsic hepatic clearance (Cl(int)), maximal secretory rate (Vmax) were provided from the analysis of the relationship between bile acid removal rates and sinusoidal concentration under steady-state conditions. TC and TUDC had the highest Cl(int) (about 5 ml/min/g liver) and Vmax (about 800 nmol/min/g liver) followed in order by GC (1.71 ml/min/g liver; 442 nmol/min/g liver); C (1.25 ml/min/g liver; 252 nmol/min/g liver); HDC (0.86 ml/min/g liver; 238 nmol/min/g liver); UDC (0.72 ml/min/g liver; 176 nmol/min/g liver). The findings suggest that the efficiency of the overall hepatic transport of bile acids is highly dependent on their molecular structure and that conjugation has a more important effect on both Cl(int) and Vmax that the number or position of hydroxyl groups.

Animals↗
PubMed1988

The healing of colonic anastomoses after early intraperitoneal chemotherapy: an experimental study in rats.

Early postoperative intraperitoneal administration of 5-fluorouracil (5-Fu) is a logical adjuvant treatment of patients with resectable colonic cancers. It is easier and less invasive than the intraportal administration of the drug. However, before applying the procedure to humans it must be demonstrated than it does not disturb the healing of recent colonic anastomoses. Colonic sutures were performed in 78 male Wistar rats. The animals then either served as controls or received intraperitoneal 5-Fu during 5 days starting on the first, third, or seventh postoperative day. No statistical difference was observed between treated and control groups when observing the incidence of anastomotic spontaneous disruptures, anastomotic healing strength, or the weight of the animals. It is concluded that early intraperitoneal 5-Fu administration does not impair the healing of recent colonic anastomoses in rats.

Anastomosis, Surgical↗
PubMed1988

Relationship among beta-adrenergic blockade, propranolol concentration, and liver function in patients with cirrhosis.

In 20 patients with cirrhosis we studied the relationship among the efficiency of beta-adrenergic blockade induced by oral administration of 40 mg propranolol, the plasma level of propranolol, and the liver function. The beta-adrenergic blockade was studied 2 h and 8 h after propranolol administration and assessed by the cardiac chronotropic response to isoprenaline. Liver function was evaluated by a standard liver function test and the Child-Turcotte or Pugh score. The beta-adrenergic blockade and propranolol plasma concentration were higher 2 h than 8 h after propranolol administration. The beta-adrenergic blockade and the propranolol plasma concentration varied widely among patients. No significant correlation was found between the efficiency of beta-blockade and propranolol concentration. The beta-adrenergic response before propranolol administration was correlated with bilirubin level and Child scores, but no significant correlation was found between the beta-blockade and the severity of liver disease. These results suggest that in patients with cirrhosis, differences in response to propranolol are not related to differences in the severity of the liver disease or to differences in propranolol concentration.

Female↗
PubMed1988

Differential response of normal and cirrhotic liver to vasoactive agents. A study in the isolated perfused rat liver.

In cirrhosis, endogenous vasoactive agents could act as modulators of intrahepatic resistance and thus portal pressure. The aim of this work was to study the effects of norepinephrine, angiotensin II and arg8-vasopressin on intrahepatic portal resistance in isolated perfused livers from normal rats and rats with carbon tetrachloride-induced cirrhosis. Livers were perfused at a constant pressure and the measured variable was portal blood flow. Dose-response curves were obtained by cumulative addition of agonists to the perfusate. The three vasoactive agents increased resistance in normal and cirrhotic livers. The maximal amplitude of response was similar in normal and cirrhotic livers. The cirrhotic livers exhibited an increased sensitivity to norepinephrine, a decreased sensitivity to angiotensin II but an unchanged sensitivity to arg8-vasopressin. The shape of the dose-response curve for norepinephrine and arg8-vasopressin, but not for angiotensin II, was modified in cirrhotic livers. We conclude that the cirrhotic liver retains a strong vascular reactivity to vasoactive agents and particularly to norepinephrine.

Algorithms↗
PubMed1987

Is ursodeoxycholic acid an effective treatment for primary biliary cirrhosis?

The effects of ursodeoxycholic acid (UDCA, 13-15 mg/kg body weight daily) were prospectively evaluated in fifteen patients with primary biliary cirrhosis (PBC). The mean concentration of UDCA in serum expressed as the percentage of total bile acids rose from 0% at baseline to 58% (SEM 9%) after 2 years' treatment, whereas total serum bile acid levels did not change significantly. The proportion of patients with pruritus necessitating the use of cholestyramine was significantly lower at 2 years than at baseline. Standard liver function tests improved in all the patients. At 2 years the average activities of gamma-glutamyltranspeptidase, alkaline phosphatases, and alanine aminotransferase and bilirubin levels were reduced (respectively 78%, 65%, 68%, and 36% of pretreatment values). In three patients who agreed to interrupt the ingestion of UDCA for 3 months after 2 years' treatment there was clear deterioration in liver function tests, which again improved after reinstitution of UDCA. These results suggest that long-term UDCA might be a safe and effective treatment for PBC, but a randomised, controlled, double-blind trial is urgently needed.

Adult↗
PubMed1987

Hepatic extraction, metabolism and biliary excretion of doxorubicin in the isolated perfused rat liver.

The hepatic extraction, metabolism, and biliary excretion of doxorubicin (DX) were studied in the isolated perfused rat liver. Three doses of DX equivalent to 2, 20, and 100 mg/kg in rats were studied over a period of 3 h after bolus injection into the reservoir. DX and metabolites concentration in perfusate, bile, and liver were determined by high-pressure liquid chromatography. The hepatic extraction ratio was low (less than 0.24) and decreased progressively over the 3 h. The hepatic extraction and clearance were significantly lower at the highest dose. Doxorubicinol (DX-OL) was the only metabolite detected in the perfusate, accounting for less than 4% of the total AUC. Thirty-one to thirty-three percent of the dose was excreted into bile over 3 h as unchanged DX. This was reduced to 22% at the highest dose. Only 0.35%-1.33% of the dose was excreted as DX-OL. DX aglycones were found only in the liver, where they represented 20%-30% of the total fluorescence at 3 h. In conclusion, in this model DX has a low extraction ratio, is poorly metabolized and extensively excreted into bile.

Animals↗
PubMed1987

Hepatic uptake of sex steroids in men with alcoholic cirrhosis.

We attempted to determine to what extent the degree of liver function impairment might affect the hepatic uptake and, as a consequence, alter the systemic plasma levels of endogenous sex steroids in male patients with alcoholic cirrhosis. The plasma levels and hepatic uptake of the steroids dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone, estrone, estradiol, progesterone, and 17-hydroxyprogesterone were assessed. Systemic plasma levels of testosterone and dehydroepiandrosterone were significantly (p less than 0.05) reduced, whereas those of androstenedione, estrone, and estradiol were significantly (p less than 0.05) elevated in men with alcoholic cirrhosis when compared to controls. Sex hormone binding globulin levels were also significantly elevated (p less than 0.01). The hepatic uptake of sex steroids depended on the degree of liver function impairment as shown by the linear significant relationship between their hepatic extractions and that of indocyanine green (r = 0.74-0.92, p less than 0.05; except for dihydrotestosterone, r = 0.17, not significant). In addition, the hepatic uptake of sex steroids depended on the binding affinity to sex hormone binding globulin. The higher the affinity for sex hormone binding globulin, the lower the hepatic uptake influenced by liver function impairment. It was estimated that hepatic clearances accounted for only 20%-50% of the metabolic clearance of sex steroids. No significant relationship between plasma levels of sex steroids and their hepatic clearance was found. We show here that in alcoholic cirrhosis the extent of hepatic uptake of sex steroids depends partly on the degree of liver function impairment and partly on the degree to which they are bound to sex hormone binding globulin. Production rate or peripheral metabolism, or both, rather than hepatic uptake alone may account for the altered circulating levels of sex steroids.

Adult↗
PubMed1987

Norepinephrine: a potential modulator of the hepatic transport of taurocholate. a study in the isolated perfused rat liver.

The effects of norepinephrine on portal blood flow hepatic extraction and intrinsic clearance of taurocholate were studied in the isolated perfused rat liver. Livers were perfused at a constant pressure. [14C]Taurocholate was infused continuously at a rate of 0.6 mumol/min. Then, three increasing doses of norepinephrine were added to the perfusate. Norepinephrine induced a significant dose-dependent reduction in portal blood flow. In spite of this reduction, taurocholate extraction did not increase and intrinsic clearance decreased significantly. When portal blood flow was decreased mechanically, intrinsic clearance was, as expected, flow-independent. The effects of norepinephrine on portal blood flow and intrinsic clearance were antagonised by phentolamine but not by propanolol. Norepinephrine decreases independently both portal blood flow and the vectorial transport of taurocholate. These effects are mediated by alpha adrenergic receptors.

Animals↗
PubMed1986

Metabolism of doxorubicin and epirubicin in adult human hepatocytes in culture.

Epirubicin is the only anthracycline to be metabolized in humans through a glucuronidation pathway which is not observed in laboratory animals. In search of a model for the experimental study of this metabolism, we have observed that human hepatocytes in culture exhibited this pathway and could be of interest for the understanding of the metabolism of this new drug.

Cells, Cultured↗
PubMed1985

[Extensive liver cancer of undetermined origin. Diagnostic procedure].

In patients with isolated malignant tumoral hepatomegaly, the investigations performed should aim at excluding a primary carcinoma of the liver and concentrate on the search for primary tumours belonging to 2 main groups: tumours responsive to hormonal treatment or chemotherapy, and obstructive tumours amenable to local palliative measures. In all cases where simple, essentially clinical examinations fail to indicate the cause of the tumoral liver enlargement, further investigations should be based on the histopathological features of the metastases.

Hepatomegaly↗
PubMed1985

High-yield preparation of porcine hepatocytes for long survival after transplantation in the spleen.

The creation of an auxiliary liver by autotransplantation of liver parenchymal cells into the spleen has mainly been studied in rats for the treatment of acute liver failure. In order to apply this procedure to humans with chronic liver insufficiency the aim of this work was: To demonstrate that hepatocytes can survive for long periods after autotransplantation into the spleen; to increase the yield of the isolation of hepatocytes obtained from pig livers since this animal has a more fibrous liver than rats or normal humans and consequently one which is more difficult to dissociate. In 21 pigs isolated hepatocytes were obtained with in collagenase dissociation technique, the yield being 1-3 X 10(7) cells per gram of liver and the viability 70-95%. The hepatocytes survived and maintained normal morphological and histochemical characteristics up to 7 months after transplantation, the date of sacrifice of the last animal.

Animals↗
PubMed1984

Hepatic extraction of adriamycin in patients with hepatocellular carcinoma.

Adriamycin (ADR) is used in the treatment of hepatocellular carcinoma (HCC). HCC frequently occurs in association with cirrhosis of the liver. ADR undergoes an extensive hepatic metabolism and biliary secretion. Therefore ADR elimination could be impaired in patients with HCC. In this study we measured the hepatic extraction of ADR by catheterization of the hepatic veins in five patients with HCC associated with cirrhosis or chronic hepatitis. In all patients the hepatic extraction ratio of ADR was very low (less than 0.10) and in four patients it was 10% or less of that of indocyanin green. This suggests that an impairment of ADR hepatic transport exists in these patients.

Aged↗
PubMed1984

[Hepatocellular carcinoma with cirrhosis: treatment with doxorubicin. Phase II evaluation].

Twelve patients with unresectable hepatocellular carcinoma associated with cirrhosis were treated with Doxorubicin which was given intravenously (30 to 50 mg/m2) every three weeks. Six patients were given only one dose of Doxorubicin. No clinical response was observed. Five patients has serum alphafoetoprotein (AFP) determination during the treatment. AFP concentration rose in 4 patients and fell in 1 patient. Survival rate after 3 and 8 months of treatment was 58 and 33 per cent. These results suggest that Doxorubicin is not an effective treatment for hepatocellular carcinoma.

Carcinoma, Hepatocellular↗