PubMed Health⌕ Search

Biomedical subjects

Paul Calès

Publications and source records attributed to Paul Calès.

At least 19 recordsLinked to original sources
PubMed2006

Hemodynamic and antifibrotic effects of a selective liver nitric oxide donor V-PYRRO/NO in bile duct ligated rats.

AIM: To assess whether a liver specific nitric oxide (NO) donor (V-PYRRO/NO) would prevent the development of portal hypertension and liver fibrosis in rats with bile duct ligation (BDL). METHODS: Treatment (placebo or V-PYRRO/NO 0.53 micromol/kg per hour) was administered i.v. to rats 2 d before BDL (D-2) and maintained until the day of hemodynamic measurement (D26). Intra-hepatic NO level was estimated by measuring liver cGMP level. Effects of V-PYRRO/NO on liver fibrosis and lipid peroxidation were also assessed. RESULTS: Compared to placebo treatment, V-PYRRO/NO improved splanchnic hemodynamics in BDL rats: portal pressure was significantly reduced by 27% (P<0.0001) and collateral circulation development was almost completely blocked (splenorenal shunt blood flow by 74%, P=0.007). Moreover, V-PYRRO/NO significantly prevented liver fibrosis development in BDL rats (by 30% in hepatic hydroxyproline content and 31% in the area of fibrosis, P<0.0001 respectively), this effect being probably due to a decrease in lipid peroxidation by 44% in the hepatic malondialdehyde level (P=0.007). Interestingly, we observed a significant and expected increase in liver cGMP, without any systemic hemodynamic effects (mean arterial pressure, vascular systemic resistance and cardiac output) in both sham-operated and BDL rats treated with V-PYRRO/NO. This result is in accordance with studies on V-PYRRO/NO metabolism showing a specific release of NO in the liver. CONCLUSION: Continuous administrations of V-PYRRO/NO in BDL rats improved liver fibrosis and splanchnic hemodynamics without any noxious systemic hemo-dynamic effects.

Alkaline Phosphatase↗
PubMed2006

Current management of the complications of portal hypertension: variceal bleeding and ascites.

Portal hypertension is one of the main consequences of cirrhosis. It results from a combination of increased intrahepatic vascular resistance and increased blood flow through the portal venous system. The condition leads to the formation of portosystemic collateral veins. Esophagogastric varices have the greatest clinical impact, with a risk of bleeding as high as 30% within 2 years of medium or large varices developing. Ascites, another important complication of advanced cirrhosis and severe portal hypertension, is sometimes refractory to treatment and is complicated by spontaneous bacterial peritonitis and hepatorenal syndrome. We describe the pathophysiology of portal hypertension and the current management of its complications, with emphasis on the prophylaxis and treatment of variceal bleeding and ascites.

Algorithms↗
PubMed2006

Late onset of Wilson's disease in a family with genetic haemochromatosis.

We report the coexistence of Wilson's disease and genetic haemochromatosis in one family. The diagnosis of genetic haemochromatosis was established in a 52-year-old man. Among his siblings, one 57-year-old sister and one 55-year-old brother had decreased copper and ceruloplasmin levels in serum and increased urinary copper excretion. The sister shared the same human leucocyte antigen haplotypes and was homozygous for the HFE mutation C282Y, like the propositus. However, she had normal liver iron content and increased liver copper content. Her dietary copper intake was probably excessive. The association of Wilson's disease and genetic haemochromatosis is rare and has only been described twice. The onset of Wilson's disease after 50 years of age is rare; Wilson's disease should be considered in any patient with unexplained chronic liver disease; an excess in liver copper content might be induced by excessive dietary input in a susceptible individual.

Age of Onset↗
PubMed2005

Sources of variability in histological scoring of chronic viral hepatitis.

Inter-observer agreement on activity and fibrosis scores used in chronic viral hepatitis has only been studied under selected conditions. The aim of this study was to identify the sources of variability due to specimen characteristics and observers. This study included 254 liver specimens and 15 pathologists and used the Metavir score. In 44 specimens scored by 4 academic pathologists, agreement of Metavir score was good overall, but better for fibrosis (kappa = 0.59) than for activity (kappa = 0.43) and poor for lobular necrosis (kappa = 0.15). The mean agreement was better for senior (0.60 +/- 0.24) than junior pathologists (0.52 +/- 0.30, P < .05). Mean intrabserver agreement was better than inter-observer agreement (0.77 +/- 0.18 vs. 0.58 +/- 0.26, P < .01). In 157 specimens scored by 2 expert pathologists (one senior, one junior), agreement of Metavir score was only good but greatly improved after consensus reading (fibrosis: kappa = 0.48 and 0.77, activity: kappa = 0.44 and 0.70, respectively, before and after consensus). Several causes of disagreement were identified: specimen length, fibrosis class number, observer bias, and putative causes related to Metavir score or specimen. In an intercenter evaluation involving 59 specimens, 1 expert and 10 nonacademic pathologists, agreement was very poor and did not improve over 5 years for activity (kappa = 0.22-0.25) or fibrosis (kappa = 0.13-0.18). In conclusion, the level of experience (specialization, duration, and location of practice) has more influence on agreement than the characteristics of the specimen (length, fibrosis class number, miscellaneous factors). Agreement can be improved by experienced pathologist or consensus reading.

Academic Medical Centers↗
PubMed2005

A novel panel of blood markers to assess the degree of liver fibrosis.

The objective was to develop new blood tests to characterize different fibrosis parameters in viral and alcoholic chronic liver diseases. Measurements included 51 blood markers and Fibrotest, Fibrospect, ELFG, APRI, and Forns scores. The clinically significant fibrosis was evaluated via Metavir staging (F2-F4), and image analysis was used to determine the area of fibrosis. In an exploratory step in 383 patients with viral hepatitis, the area under the receiving operator characteristic (AUROC) curve for stages F2-F4 in a test termed the "Fibrometer" test combining platelets, prothrombin index, aspartate aminotransferase, alpha2-macroglobulin (A2M), hyaluronate, urea, and age was 0.883 compared with 0.808 for the Fibrotest (P = .01), 0.820 for the Forns test (P = .005), and 0.794 for the APRI test (P < 10(-4)). The Fibrometer AUROC curve was 0.892 in the validating step in 120 patients. The AUROC curve for stages F2-F4 in a test combining prothrombin index, A2M, hyaluronate, and age was 0.962 in 95 patients with alcoholic liver diseases. The area of fibrosis was estimated in viral hepatitis by testing for hyaluronate, gamma-glutamyltransferase, bilirubin, platelets, and apolipoprotein A1 ((a)R(2) = 0.645), and in alcoholic liver diseases by testing for hyaluronate, prothrombin index, A2M, and platelets ((a)R(2) = 0.836). In conclusion, the pathological staging and area of liver fibrosis can be estimated using different combinations of blood markers in viral and alcoholic liver diseases. Whereas the Fibrometer has a high diagnostic accuracy for clinically significant fibrosis, blood tests for the area of liver fibrosis provide a quantitative estimation of the amount of fibrosis, which is especially useful in cirrhosis.

Adult↗
PubMed2005

[Non-invasive diagnosis of portal hypertension in cirrhosis. Application to the primary prevention of varices].

One of the major complications of cirrhosis is the occurrence of portal hypertension and esophageal varices. At present, universal endoscopic screening of esophageal varices is recommended in association to primary prophylaxis in patients at high risk of variceal bleeding. But this screening is invasive and could be not cost-effective. Besides, pre-primary phrophylaxis is not effective and hampared by side effects. So, non invasive diagnosis of portal hypertension might be useful. This one could depend on non invasive measurement of hepatic venous pressure gradient, but its application to screening is not well-documented and its use in treatment monitoring is debated. A second way could be non invasive diagnosis of large esophageal varices because of prognostic and economic issues. Indirect echographic markers of portal hypertension and esophageal varices (ascites, portal vein diameter > or = 13 mm, spleen length, maximal and mean velocimetry of portal vein flow, respectively < 20 cm/s and < 12 cm/s) could be useful. Among this parameters, spleen length is an independent predictive marker of esophageal varices. Besides, several direct or indirect blood markers of fibrosis have been tested. Platelet count is repeatedly a predictive marker of esophageal varices in multivariate analysis. The other predictive factors of esophageal varices could be: prothrombin time, splenomegaly, spider naevi, Child-Pugh class, bilirubinemia, platelet count/spleen diameter ratio and Fibrotest, but these data require validation. In summary, in regard to actual results, non invasive diagnosis of portal hypertension might be useful in esophageal varices screening, but the substitutes to endoscopy have limited place actually in clinical practice, and exclusive non invasive diagnosis of portal hypertension is not applicable; the only test that seems to be useful in clinical practice is conventional endoscopy awaiting the results of videocapsule.

Decision Trees↗
PubMed2004

Vascular involvement of the liver in Turner's syndrome.

Unexplained liver test abnormalities are frequent in patients with Turner's syndrome. This cohort study was performed to clarify the histopathologic features, causes, and long-term outcome of liver involvement in these patients. Thirty patients with persistently abnormal liver test results were followed-up for 8.8 +/- 5.2 years. Liver specimens were available in 27 patients. Marked architectural changes were present in 10 patients, including nodular regenerative hyperplasia in six, multiple focal nodular hyperplasia in two, and cirrhosis in two patients. These changes frequently were associated with obliterative portal venopathy lesions and with aortic malformations. There was mild to moderate portal fibrosis in 15 of the 17 other patients, inflammatory infiltrates in nine patients, and nonalcoholic fatty liver disease in 11 patients. Bile duct alterations resembling small duct sclerosing cholangitis were observed in 21 patients (with or without architectural changes). There was no viral, alcoholic, autoimmune, or drug-induced liver damage. Portal hypertension was observed in four patients with marked architectural changes, including three in whom refractory ascites or recurrent variceal bleeding developed, one of whom underwent transplantation. None of the patients without marked architectural changes experienced progressive or decompensated liver disease. There was no evidence of liver toxicity from estrogen replacement therapy. In conclusion, the main causes of liver involvement in Turner's syndrome are vascular disorders, probably of a congenital origin, and nonalcoholic fatty liver disease. In patients with vascular disorders, severe liver disease requiring liver transplantation may develop. Estrogen therapy does not appear to be pathogenically implicated.

Adult↗
PubMed2004

New Doppler ultrasound signs improve the non-invasive diagnosis of cirrhosis or severe liver fibrosis.

OBJECTIVES: To determine whether ultrasound and, particularly, new Doppler signs increased the diagnostic accuracy of the most accurate, currently available markers for the diagnosis of cirrhosis or severe fibrosis. METHODS: Thirty-two clinical (n = 4), biochemical (n = 11) and Doppler ultrasound (n = 17) variables were recorded in 106 patients with compensated chronic liver disease. Diagnostic accuracy was evaluated by discriminant analysis; first, globally, using all variables then by stepwise analysis. RESULTS: (A) Diagnosis of cirrhosis. Using Doppler ultrasound, diagnostic accuracy was 92% (95% confidence interval 81-98) globally, and 89% (76-95) with three variables (spleen length, hepatic vein spectrum and maximum portal vein velocity). Based upon clinical signs, diagnostic accuracy was 86% (77-92) globally, and 85% (76-91) with one variable (firm liver). Based upon biochemical parameters, diagnostic accuracy was 80% (70-88) globally, and 81% (72-88) with two variables (hyaluronate and platelet count). Based upon all parameters, diagnostic accuracy was 91% (79-96.5) globally, and 91% (79-96.5) with four variables (firm liver, hyaluronate, platelet and hepatic vein spectrum). On an intention to diagnose basis, Doppler ultrasound provided a lower independent contribution due to missing data. (B) In the diagnosis of severe fibrosis, diagnostic accuracy was 83% (69-92) globally, and 77% (62-87) with one variable. CONCLUSIONS: Cirrhosis can be correctly diagnosed in approximately 90% of patients with compensated chronic liver disease using a few Doppler ultrasound signs including a new sign, the hepatic vein spectrum. Doppler ultrasound could be used for the first line diagnosis and biochemical markers, such as hyaluronate, in patients with missing Doppler ultrasound data.

Adult↗
PubMed2003

Respective roles of porto-septal fibrosis and centrilobular fibrosis in alcoholic liver disease.

In alcoholic liver disease, fibrosis classically begins around the centrilobular veins, while portal tract fibrosis is described as inconstant and septal fibrosis is a late event. The aim of this study was to compare the roles of centrilobular fibrosis (CLF) and portal tract/septal fibrosis (PTF) especially in alcoholic chronic liver disease. One hundred and sixty patients with alcoholic chronic liver disease and 83 controls with viral chronic hepatitis were included. The PTF score, derived from the Metavir score, CLF and the area of fibrosis, assessed by image analysis, were evaluated on liver biopsies in addition to blood markers of fibrosis. The correlation between the PTF score and the area of fibrosis was higher in alcoholic liver disease (r = 0.87, p < 10(-4)) than in viral chronic hepatitis (r = 0.66, p < 10(-4)). The PTF score correlated with the CLF score (r = 0.92, p < 10(-4)), serum hyaluronate (r = 0.76, p < 10(-4)), and the prothrombin index (r = -0.77, p < 10(-4)). Multiple regression analyses showed that the area of fibrosis was explained only by the PTF score and not by the CLF score. PTF appears more frequent than CLF in alcoholic chronic liver disease, suggesting that PTF may precede CLF. PTF is more responsible for the amount of fibrosis than CLF. The results of this study also validate the use of the Metavir fibrosis score in alcoholic chronic liver disease.

Biomarkers↗
PubMed2003

Hepatitis C, alpha interferon, anxiety and depression disorders: a prospective study of 71 patients.

This article presents a prospective study of 71 patients infected with chronic viral hepatitis C and treated with interferon alpha during one year. The objective was to assess the incidence and predictive factors of anxiety and depression symptoms during and after the therapy. Each patient received psychiatric assessment before, during and after treatment, with evaluations using Hamilton-anxiety and MADRS scales. Results confirm the great incidence of depression and anxiety not only during interferon alpha therapy but also after treatment is discontinued. Sleep disorders and MADRS ratings of M4 seem to be predictive of the therapy's side effects. Thus, there seem to be easily discernable parameters allowing depression and suicidal behaviour to be anticipated. This paper emphasises their possible occurrence after the treatment and, therefore, the need for routine assessments after treatment is discontinued. Teams comprising both hepatologists and psychiatrists should complete these assessments. This shows the necessity of interdisciplinary collaboration treatment of this kind.

Antiviral Agents↗
PubMed2003

Low-dose terlipressin improves systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats.

OBJECTIVE: Vasopressin has been used to treat arterial hypotension associated with hyperdynamic vasoplegic states, but detrimental effects on splanchnic circulation have been reported. We tested the effects of a low-dose vasopressin analogue, terlipressin (6 microg/kg), on systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats (lipopolysaccharide, 30 mg/kg in 1 hr). DESIGN: Prospective, randomized, controlled experimental study with repeated measures. SETTING: Investigational animal laboratory. SUBJECTS: A total of 77 rats were divided into five groups: group C, control (17 rats); group E, LPS (18 rats); group EF, LPS plus fluid challenge (18 rats); group EFT, LPS plus fluid challenge plus terlipressin (18 rats); and group ET, LPS plus terlipressin (seven rats). INTERVENTIONS: Rats were anesthetized, mechanically ventilated, and instrumented to measure heart rate, mean arterial pressure, and abdominal aortic and mesenteric vein indexed blood flows; ileal microcirculation was assessed by laser Doppler. After LPS infusion, rats experienced an endotoxic shock and were resuscitated after the allocation group. The fluid challenge was targeted to maintain mean arterial pressure of >90 mm Hg and aortic blood flow at baseline values. MEASUREMENTS AND MAIN RESULTS: Terlipressin significantly (p <.05) increased mean arterial pressure without decreasing indexed aortic blood flow and heart rate in the fluid-challenged endotoxic rats (EFT) compared with EF rats and had detrimental effects in hypodynamic endotoxic rats (ET). Fluid challenge significantly (p <.05) increased mesenteric vein blood flow in both the EF and EFT groups, and terlipressin had no detrimental effect on mesenteric blood flow. Terlipressin significantly (p <.05) increased ileal microcirculation in fluid-challenged endotoxic rats (EF and EFT) but not in hypodynamic endotoxic rats (E and ET). CONCLUSION: Low-dose terlipressin in fluid-challenged endotoxic rats improved systemic and splanchnic hemodynamics and improved the ileal microcirculation.

Animals↗
PubMed2003

Inter-observer and intra-observer variability in hepatology.

OBJECTIVES: A determination of the inter-observer variability is an important step before determining diagnostic accuracy and requires a specific methodology and statistical tests. The aim of this study was to report the results, characteristics and methodological quality of agreement studies performed in hepatology. METHODS: A search of published studies yielded 42 that could be used in this evaluation: three were clinical studies, 11 were in the field of endoscopy, 12 in histopathology and 16 in radiology. The studies were described with a grid of 28 items and evaluated with a quality score (QUAS; maximum, 35) including 22 items. RESULTS: The following agreement level was noted: intra-observer > inter-observer > inter-centre. The following signs had good agreement. Endoscopy: size and red signs of oesophageal varices; histopathology: cirrhosis, fibrosis and steatosis; Doppler: mean portal vein and superior mesenteric artery velocities, hepatic artery area and perfusion indexes. Frequent methodological weaknesses were noted. The real agreement (such as the kappa index excluding chance), and the prevalence of signs and biases were rarely assessed. Standardized observations (67% of the studies), blind assessment (48%), simultaneous observations (7%), and the recording technique were not frequently used. The mean QUAS was 13 +/- 6 with 17 +/- 4 in histopathology versus 11 +/- 6 in radiology (P < 0.05). Using multiple regression, four variables independently predicted the QUAS with R2 = 0.77: adapted tests, multiple observations, intra-class correlation coefficient and agreement proportion. CONCLUSIONS: Methodology was often insufficient. Agreement is often measured under biased conditions. Some areas were not or were rarely studied, e.g., biology and ultrasound. The agreement and QUAS were often poor, suggesting the need for studies with improved observation and methodological quality of agreement.

Esophageal and Gastric Varices↗
PubMed2003

[1,1, 1-trichloroethane-induced chronic active hepatitis].

1,1, 1-trichloroéthane is derived from carbon tetrachloride and has been widely used as an industrial solvent since 1954, because of its supposed lack of toxicity. However, several cases of central nervous system toxicity and heart disorders due to intoxication by 1,1, 1-trichloroéthane have been reported. Cases of liver injury are infrequent, with less than 10 cases, unlike 1,1, 2-trichloroéthane that it replaced. We report a case of hepatotoxicity probably due to 1,1, 1-trichloroéthane exposure, characterized by an original pathologic feature of chronic active hepatitis.

Adult↗