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Biomedical subjects

B Champigneulle

Publications and source records attributed to B Champigneulle.

At least 19 recordsLinked to original sources

Short-term cardiovascular effects of somatostatin in patients with cirrhosis.

Somatostatin is used to treat variceal hemorrhage in patients with cirrhosis and portal hypertension. Its systemic hemodynamic effects, however, are not yet well defined. Since cardiomyopathy or pulmonary artery hypertension may occur in patients with cirrhosis, definition of the systemic hemodynamic effects of somatostatin or its analogue octreotide is of clinical importance. The aim of this study was to evaluate the effects of somatostatin, at different doses and under different conditions of administration, on the systemic hemodynamics in 17 patients with cirrhosis. Two sets of experiments were performed. In the first, eight patients received two different bolus doses (100 and 250 micrograms) of somatostatin. The second set of experiments was designed to study the hemodynamic effects of the combination of a bolus and an infusion of somatostatin. Nine other patients received one bolus of 250 micrograms of somatostatin, followed by a 250 micrograms/h infusion for 65 min. A second bolus of 250 micrograms of somatostatin was injected in these patients after 35 min of infusion. Before and for 30 min after each bolus, systemic hemodynamics were measured. Following a bolus of somatostatin, a dose-dependent decrease in heart rate (from 77 +/- 3 to 73 +/- 5 beats/min with 100 micrograms, and from 78 +/- 4 to 68 +/- 5 beats/min with 250 micrograms, p < 0.05) and increases in systemic and pulmonary artery pressures were observed. The combination of an infusion and a bolus of somatostatin significantly reduced the increases in systemic and pulmonary artery pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Studies on peroxisomes of colonic mucosa in Crohn's disease.

The etiology and pathogenesis of Crohn's disease, a chronic inflammatory bowel pathology, have not been elucidated yet. In particular, the behavior of peroxisomes in inflamed colonic mucosa has not been investigated despite their important role in cellular oxidative metabolism. Using cytochemistry at the ultrastructural level, we have observed these catalase-positive organelles. In addition, biochemical analyses have revealed the specific activities of catalase and cyanide-insensitive acyl-CoA oxidase. Mucosal biopsy specimens from inflamed and noninflamed areas of Crohn's patients were compared to control biopsies. We found that Crohn's disease was marked by an important diminution in the peroxisomal frequency per cell unit area. If catalase activity was not affected by this pathology, cyanide-insensitive acyl-CoA oxidase, an enzyme of the peroxisomal beta-oxidation system, was found diminished in inflamed and in noninflamed areas. In conclusion, our results showed that Crohn's disease is accompanied by peroxisomal modifications but the number and the enzyme activities of colonic peroxisomes are less deeply altered in Crohn's disease than during neoplasia. This fact suggests that a relation may exist between the degree of peroxisomal deficiency and the clinical severity of colonic disease.

Acyl-CoA Oxidase

Total effective vascular compliance in patients with cirrhosis: a study of the response to acute blood volume expansion.

Although arterial vasodilation is a well-known feature in patients with cirrhosis, the venous system remains unexplored. To measure total effective vascular compliance, a reflection of the properties of the venous system, rapid volume expansion (300 ml of a gelatin solution in 3 min) was performed in 23 patients. Eleven patients had compensated cirrhosis (Child-Pugh grade A or B), and eight had decompensated cirrhosis (Child-Pugh grade C). Four control patients had mild chronic hepatitis, normal hepatic venous pressure and normal liver architecture. Cardiac index, hepatic venous pressures, hepatic and azygos blood flow and renal plasma flow were measured before and immediately after volume expansion. Right atrial pressure was recorded during volume expansion. This allowed the calculation of total effective vascular compliance, which was higher in patients with decompensated cirrhosis than in those with compensated cirrhosis (4.65 +/- 4.21 vs. 1.34 +/- 0.63 ml.mm Hg-1.kg-1; p less than 0.05). In response to volume expansion, renal vascular resistance decreased significantly in patients with compensated cirrhosis, but not in those with decompensated cirrhosis (-30% +/- 33% vs. +2% +/- 23%; p less than 0.05). No change was seen in glomerular filtration rate. Systemic oxygen consumption increased in patients with compensated cirrhosis, but not in those patients with decompensated cirrhosis (25% +/- 33% vs. -4% +/- 9%; p less than 0.05). Although in all patients with cirrhosis volume expansion increased central venous pressures, azygos blood flow and the hepatic venous pressure gradient did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Hemodynamic effects of endotoxin and platelet activating factor in cirrhotic rats.

Acute infections may influence the hemodynamic alterations of liver disease. Therefore, the hemodynamic effects of endotoxin (LPS E. coli 0111:B4) in conscious, normal, and cirrhotic rats were compared. Endotoxin decreased cardiac index in cirrhotic but not in normal rats. Although the effect of endotoxin on portal tributary blood flow was minor in all animals, a reduction in portal pressure was found in cirrhotic rats. Because the most marked hemodynamic effects were observed in cirrhotic rats, the second part of our study investigated whether platelet activating factor played a role in endotoxin-induced hemodynamic alterations in the cirrhotic model. Platelet activating factor reduced cardiac index and kidney blood flow but did not influence portal tributary blood flow. Two antagonists to platelet activating factor reduced the adverse renal blood flow lowering effects of endotoxin in cirrhotic rats. Thus, it is suggested that the hemodynamic changes observed in cirrhosis may be aggravated during acute infections. Under this condition, antagonists to platelet activating factor may be of benefit in the prevention of hemodynamic complications induced by endotoxin.

Animals

Effects of theophylline on hemodynamics and tissue oxygenation in patients with cirrhosis.

Since adenosine may play a role in the hyperdynamic circulation of cirrhosis, we examined the effects of theophylline (an adenosine receptor antagonist) on systemic and splanchnic hemodynamics, tissue oxygenation and sympathoadrenal activity in patients with cirrhosis and liver failure. Theophylline (aminophylline) was administered intravenously for 30 min. Six patients received a dose of 3 mg/kg and eight others a dose of 6 mg/kg. The low dose caused plasma theophylline concentrations of 7.4 +/- 1.8 mg/ml (mean +/- S.E.), and induced a significant increase in heart rate from 84 +/- 5 to 93 +/- 8 beats/min. This dosage did not significantly change other hemodynamic values, oxygen (O2) consumption, or sympathoadrenal activity. The high dose elicited plasma theophylline concentrations of 15.8 +/- 4.0 mg/ml. This dose significantly increased heart rate from 78 +/- 5 to 87 +/- 7 beats/min and significantly decreased right atrial pressure from 2.5 +/- 1.0 to 1.4 +/- 0.8 mmHg, stroke volume from 52 +/- 3 to 47 +/- 5 ml.beat-1.m-2 and systolic arterial pressure from 140 +/- 5 to 129 +/- 6 mmHg. In contrast, O2 consumption, sympathoadrenal activity, and all other hemodynamic values (including azygos blood flow) were not significantly modified. As a result, we conclude that, in patients with cirrhosis, theophylline may cause decreased stroke volume which lowers systolic arterial pressure. In our patients theophylline also had a positive chronotropic effect but no vasoconstrictor effect on systemic and splanchnic circulation. Finally, theophylline did not improve tissue oxygenation in patients with cirrhosis.

Adult

Hemodynamic and sympathetic responses to human atrial natriuretic peptide infusion in patients with cirrhosis.

To determine the potential usefulness of atrial natriuretic peptide (ANP) in patients with cirrhosis, we examined the effects of the infusion of a low dose of alpha-human ANP (alpha hANP, 25 ng.kg-1.min-1 for 30 min) on renal, splanchnic, systemic hemodynamics and sympathetic outflow in eight patients. Pulmonary arterial plasma ANP concentrations increased from 59 +/- 9 to 328 +/- 41 pg/ml (mean +/- S.E., p less than 0.05). Mean values of glomerular filtration rate and renal plasma flow were not significantly changed. Individual renal plasma flow responses differed from one patient to another. Renal plasma flow increased in two patients, decreased in three and did not change in the other patients. Renal plasma flow changes were correlated with basal renal plasma flow values (r = -0.938, p less than 0.05) but not with arterial pressure changes or renal vein plasma norepinephrine concentration changes. Azygos blood flow increased from 0.43 +/- 0.10 to 0.63 +/- 0.13 l/min (p less than 0.05) and the hepatic-venous pressure gradient decreased from 19.9 +/- 1.5 to 17.5 +/- 2.9 mmHg in post-infusion (p less than 0.05). Mean arterial pressure decreased significantly by 18% and cardiac output by 12%. Systemic vascular resistance and pulmonary arterial plasma norepinephrine concentrations were not significantly modified. Thus, in patients with cirrhosis, alpha hANP appears to have a direct vasodilating action on renal arterioles when basal renal vascular tone is high. In addition, although alpha hANP might exert a portal hypotensive action, alpha hANP induced arterial hypotension as a result of both low cardiac output and a lack of increased sympathetic vascular tone. The arterial hypotensive action may, thus, limit the therapeutic use of low doses of alpha hANP in cirrhotic patients.

Aldosterone

Relationship of insulin resistance to protein-energy malnutrition in patients with alcoholic liver cirrhosis: effect of short-term nutritional support.

Protein-energy malnutrition (PEM) and insulin resistance (IR) are common features of alcoholic liver cirrhosis (ALC). In order to determine a relationship between them, nutritional status and glucose homeostasis were studied in 26 patients with ALC. Nutritional status was assessed through dietary, anthropometric, and biological parameters. An IR index (M/I) was obtained from the euglycemic insulin clamp technique. M/I was significantly correlated with accurate markers of PEM (albumin, transthyretin, and retinol-binding protein) but not with other markers of liver dysfunction. Nine patients were studied before and after nutritional support: M/I was significantly improved as were serum markers of PEM. Other markers of liver dysfunction were also significantly improved. These findings suggest that PEM could be responsible, in part, for IR in patients with ALC who are frequently malnourished. Moreover, nutritional support improved insulin sensitivity in these patients.

Anthropometry

Adenosine and hemodynamic alterations in cirrhotic rats.

This study evaluated the hypothesis that adenosine may participate in the hemodynamic alterations observed in conscious unrestrained cirrhotic rats. In sham-operated rats, adenosine (20 micrograms.100 g body wt-1.min-1 iv) induced hyperdynamic circulation and significantly increased portal pressure, mimicking the hemodynamic changes observed in cirrhosis. Although adenosine significantly increased hyperdynamic circulation and portal pressure in cirrhotic rats, these changes were significantly less marked than in sham-operated rats. 8-Phenyltheophylline (20 micrograms.100 g body wt-1.min-1 iv), a specific and potent adenosine antagonist, significantly decreased portal tributary blood flow in sham-operated rats (-18.0 +/- 5.6%) but did not have a significant effect in cirrhotic rats. The limited effect of 8-phenyltheophylline was not due to an insufficient dose, since the dose administered antagonized the hemodynamic effect of exogenous adenosine up to 40 micrograms.100 g body wt-1.min-1. We conclude that in certain circumstances, although adenosine may aggravate the hyperdynamic circulation, in normal conditions, the hemodynamic alterations observed in cirrhotic rats are not mediated by adenosine.

Adenosine

Blood transcobalamin levels in malignant hepatoma.

Alpha-Fetoprotein (AFP) levels measured by RIA show a strong sensitivity for the biological diagnosis of malignant hepatoma (MH). However, this parameter lacks specificity. Previous observations of an alteration in vitamin B12 metabolism in the presence of hepatoma led us to study vitamin-B12-binding proteins. Vitamin B12, also called cobalamin, is transported in the blood by two proteins or transcobalamins: one is haptocorrin (HC), which is linked to most of the cobalamin, and the other is transcobalamin II, which is involved in tissue exchanges. In this work, the levels of AFP and transcobalamins were determined by RIA and radioisotope dilution assay, respectively. They were measured in patients with MH (group A) and in patients with other liver diseases (group B). Compared with group B, group A showed a significant increase in total serum HC (p less than 0.005). In conclusion, it was observed that MH is accompanied by increased levels of HC. The origin of these changes could be due to either an increase in HC synthesis or a catabolic defect.

Carcinoma, Hepatocellular

Malabsorption of vitamin B12 in pancreatic insufficiency of the adult and of the child.

Vitamin B12 can bind two carrier proteins in the digestive tract, haptocorrin (R binder) and intrinsic factor, but only its binding to intrinsic factor allows its absorption. A malabsorption of vitamin B12 is observed in about 30% of adult patients with exocrine pancreatic insufficiency, using the Schilling test. None of the hypotheses that have tried to explain this malabsorption are entirely satisfactory. A failure to degrade haptocorrin can prevent the binding of vitamin B12 to intrinsic factor. It has also been suggested that pancreatic secretion could modify the structure of intrinsic factor, enabling the uptake of the vitamin B12-intrinsic factor complex by the ileum. Other factors can also affect the binding of vitamin B12 to intrinsic factor, such as the gastric pH and bile. The Schilling test is abnormal in nearly all cases of cystic fibrosis. One explanation could be the gastric hyperacidity observed in this disease. Despite the frequency of abnormal Schilling tests, vitamin B12 deficiency is very rare in cases of exocrine pancreatic dysfunction, in adults as well as in children with cystic fibrosis. The assimilation of this vitamin with a tracer included in food instead of the crystalline labeled cobalamin used in the Schilling test remains to be investigated.

Adult

Evaluation of fibrosis in the disse space in noncirrhotic alcoholic liver disease.

In 40 alcoholic noncirrhotic patients, we performed a liver biopsy and determined the wedged hepatic vein pressure, the free hepatic vein pressure, and the intrahepatic vein pressure. In 27 of them, the serum concentration of the N-terminal peptide of type III procollagen (PIIIP) and of the laminin P1 fragment was measured. All the liver biopsies were studied by light and transmission electronic microscopy. A score of collagenization of the Disse space (six classes) was performed using transmission electronic microscopy. 37 of the 40 patients had pathological collagenization of the Disse space which was correlated with intrahepatic pressure (p less than 0.01). The lamin P1 blood level in patients (1.38 +/- 0.51 U/ml) was increased, compared to the values of our controls (0.99 +/- 0.10 U/ml, p less than 0.01) and was correlated with the wedge hepatic vein pressure (p less than 0.01). The PIIIP blood level was not significantly increased except when Mallory bodies were found in hepatocytes (p less than 0.05). The laminin P1 blood level seemed to be a good biological marker for detection of liver fibrosis in long-term alcoholic intake.

Adult

[Prospective study of the function of the anal sphincter before and after hemorrhoidectomy].

A prospective study was carried out on the anorectal function in patients with hemorrhoids (group H, n = 25) versus normal controls (group T, n = 22) and on the effect at three months of hemorrhoidectomy on sphincter function and anal continence. Hemorrhoidectomy was performed by the same surgeon using the standard Milligan Morgan procedure in all cases. All patients and controls underwent an anal manometry, a measure of the length of the anal sphincter and a saline continence test. Anal resting pressure was higher in group H as compared to group T before hemorrhoidectomy (136 +/- 32 cm H2O vs 98 +/- 19 p less than 0.001). After hemorrhoidectomy, and resting pressure was significantly lower (141 +/- 21 cm H2O vs 106 +/- 25 p less than 0.01). Anal length was similar in group H and in group T (50.2 +/- 6.6 mm vs 45 +/- 5.5 NS) but decreased significantly after hemorrhoidectomy (41.9 +/- 7.6 vs 50.3 +/- 7.3 p less than 0.01). Ultraslow waves were more often observed in patients with piles (60 p. 100 vs 9 p. 100 of normal controls). After hemorrhoidectomy ultraslow waves were less commonly encountered (25 p. 100 p less than 0.05). Anal leakage during the saline continence test was observed in 12 and 82 p. 100 of patients before and after hemorrhoidectomy, respectively (p less than 0.001). No anal leakage was observed in the control groups. After hemorrhoidectomy the mean volume of anal leakage was of 190 ml. In 35 p. 100 of the patients, anal leakage occurred before the anal infusion of 500 ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Interobserver and intercenter agreement of gastro-esophageal endoscopic signs in cirrhosis. Results of a prospective multicenter study].

Because of the diagnostic and prognostic value of gastroesophageal endoscopic signs in cirrhosis, we studied their interobserver and intercenter agreement. Fifty cirrhotic patients without previous digestive bleeding were included in this study. The gastroesophageal endoscopic examinations of these patients, recorded on video tape, were independently viewed by 12 observers belonging to different hospitals. Agreement was evaluated by the kappa index (k), the values of which were given with p less than 0.001. Agreement was good for the presence (k = 0.40) or the size (k = 0.51) of esophageal varices as well as for red signs on the mucosa overlying esophageal varices, but it was poor for the color (k = 0.10) or the extent (k = 0.20) of esophageal varices. Agreement was poor for all gastric signs: fundic varices (k = 0.35), red spots (k = 0.28), associated lesions (k = 0.27), mosaic pattern (k = 0.27), gastropathy (k = 0.11). The mean diameter of esophageal varices, evaluated without any scale, varied from 3.5 +/- 1.4 to 7.5 +/- 4.0 mm between the 12 observers (p less than 0.001). Agreement was maximum for the more developed grade of a sign and minimum for the intermediate grade. The value of kappa indexes in this intercenter study was compared to that obtained in a previous study from one institution: interobserver agreement was significantly better within one center than between different centers. In conclusion, intercenter agreement is good for the size of esophageal varices and the presence of red signs, and poor for all the other signs. The millemetric measurement of esophageal varices diameter, without any scale, appears to be unreliable.(ABSTRACT TRUNCATED AT 250 WORDS)

Esophageal and Gastric Varices

[Evaluation of exocrine pancreatic function by the haptocorrin degradation test of the duodenal fluid collected by endoscopy].

Two groups of biological methods are commonly used to evaluate the exocrine pancreatic function: tests which require tubes for the collection of duodenal juice and the tubeless tests which are indirect tests of pancreatic function. In this study we have attempted to improve a new test: the test of haptocorrin degradation (THD). This test measures the transfer of labelled cobalamin from haptocorrin to the intrinsic factor which is provoked by the degradation of the haptocorrin by proteases in the duodenal juice. We present the results of this test in 90 patients with chronic pancreatitis. THD was first assayed with basal duodenal juice collected by naso duodenal tubing during secretin cerulein stimulation. In this study the sensitivity and specificity of THD was 0.86 and 0.93, respectively. In the second part of this study we demonstrated that the means of collecting duodenal juice had no effect on the results of THD. Duodenal juice was collected during a secretin cerulein test or during a routine upper gastrointestinal endoscopy after pancreatic stimulation with secretin. The sensitivity and specificity of THD was 0.90 and 0.94, respectively, when duodenal juice was collected during endoscopy. THD was significantly correlated with the NBT-PABA test, steatorrhea, and with the activity of trypsin and chymotrypsin in the duodenal juice. In this study, NBT-PABA was less sensitive than THD for the diagnosis of chronic pancreatitis (sensitivity was 0.70 and 0.89, respectively). The specificity of THD was estimated at 0.94. THD seemed to be a valuable adjunct to test pancreatic function. As upper gastrointestinal endoscopy is usually performed in patients with proved or suspected chronic pancreatitis, THD seems to have a place of choice among the other tests of pancreatic exocrine function. Further evaluation of this test by a multicentric prospective trial is now needed.

Adult