Paolo Buonamico

Interobserver and interequipment variability of hepatic, splenic, and renal arterial Doppler resistance indices in normal subjects and patients with cirrhosis

BACKGROUND/AIMS Doppler arterial resistance indices are used to evaluate alterations in arterial hemodynamics in the liver, spleen, and kidney. The purpose of this study was to determine the interobserver and interequipment variability of hepatic, splenic, and renal arterial Doppler resistance indices, and the influence of a cooperative training program of the operators on the reproducibility of the results. METHODS In the first part of the study, hepatic (PI-L, RI-L), splenic (PI-S, RI-S), and renal (PI-K, RI-K) pulsatility and resistive indices were measured by echo-color-Doppler in eight control subjects and ten patients with cirrhosis by three operators using three different machines. In the second part of the study, measurements were taken by the three operators in nine controls and nine patients with cirrhosis, after cooperative training, with a single machine. RESULTS Significant interobserver variability was present for all parameters except RI-L. Significant interequipment variability was present for all parameters except PI-S and RI-S. Only 0-3% of variance was equipment- or operator-related, while 58-72% was patient-related. Hepatic and renal coefficients of variation were similar in patients with cirrhosis and controls, while splenic coefficients of variation were higher in patients with cirrhosis than in controls. After training, differences among operators disappeared for all variables except RI-K, and the operator-related component of variance nearly disappeared for all parameters. CONCLUSIONS Hepatic, splenic, and renal arterial resistance indices show small but significant interobserver and interequipment variability. Interobserver variability can be decreased to non-significant levels by a common training program. Thus, these indices can be widely applied to the study of arterial circulation in these organs.

Oxidation of circulating proteins in alcoholics: role of acetaldehyde and xanthine oxidase

BACKGROUND/AIMS This study aimed to evaluate the protein and lipid redox status in plasma erythrocytes and erythrocyte ghosts of alcoholics and of patients with non-alcoholic liver disease; we also investigated the relation to glutathione levels and the role of acetaldehyde and xanthine oxidase activity in plasma. METHODS Carbonyl and sulfhydryl proteins, glutathione and malondialdehyde levels and the activity of the circulating xanthine oxidase were determined in: active and abstinent alcoholics, patients with chronic viral hepatitis and healthy controls. RESULTS Active alcoholics showed a decrease of sulfhydryl protein and glutathione concentrations in plasma, erythrocytes and ghosts compared to the other groups. Also, an increase of the carbonyl protein and malondialdehyde levels and of the activity of circulating xanthine oxidase (9.2 +/- 1.8 nmol.min.ml, p < 0.001) were observed. Significant correlations between carbonyl protein and malondialdehyde concentrations in plasma (r = 0.775, p < 0.001), as well as between daily alcohol intake and carbonyl protein content in plasma (r = 0.879, p < 0.001) and erythrocytes (r = 0.605, p < 0.01) were observed. However, carbonyl protein levels did not correlate with the degree of liver injury. Incubation of plasma with acetaldehyde, but not with ethanol, significantly increased the carbonyl protein formation. Administration of N-Ethylmaleimide, a thiol depletor, or glutathione significantly increased or delayed, respectively, the carbonyl protein formation. CONCLUSIONS Proteins are oxidatively modified in plasma and erythrocytes of active alcoholics, whereas no such alterations are detectable in patients with non-alcoholic liver disease. Protein oxidation in alcoholics does not seem to result directly from ethanol; circulating xanthine oxidase, delivered from injured cells, may play a contributory role and glutathione appears to be directly involved in the protection of plasma proteins against acetaldehyde toxicity.

Hepatic involvement in hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is an autosomal-dominant vascular disease characterized by mucocutaneous or visceral angiodysplastic lesions (telangiectases and arteriovenous malformations) that may be widely distributed throughout the cardiovascular system. The recognition of mucocutaneous telangiectases, the occurrence of spontaneous and recurrent episodes of epistaxis, the presence of visceral involvement, and a family history of this disease are the clinical criteria that allow diagnosis. In comparison with skin, lungs, gastrointestinal tract, and brain involvement, hepatic involvement defined by clinical criteria alone has long been considered uncommon. Our experience with a large group of HHT patients, even those asymptomatic for liver involvement, demonstrates that it is more frequent than reported and is characterized by the presence of intrahepatic shunts, disseminated intraparenchymal telangiectases, and other vascular lesions. Congestive cardiac failure, portal hypertension, portosystemic encephalopathy, cholangitis, and atypical cirrhosis have been reported as possible serious complications related to this condition. Thus, a correct diagnosis is important, and diagnostic imaging has a fundamental role in detecting alterations involving the liver. The possibilities to perform a multiphasic study and to provide high-quality multiplanar and angiographic reconstructions, gives multidetector row helical computed tomography the ability to detect and characterize the complex anatomopathologic alterations typical of this disease.

Haemodynamic effects of propranolol, octreotide and their combination during fasting and post-prandial splanchnic hyperaemia in patients with cirrhosis.

Background/aims This double-blind study was designed to evaluate the haemodynamic effect of two drugs, propranolol and octreotide, and their combination in patients with cirrhosis. Methods Fifteen patients with cirrhosis were randomly assigned to two groups receiving either octreotide subcutaneously at 100 μg (`octreotide’ group, n = 9) or propranolol orally at 40 mg followed by a subcutaneous dose of octreotide (100 μg) after 1 h (`propranolol + octreotide’ group, n = 6); then, after 30 min, a standard meal was administered to both groups. The hepatic vein pressure gradient by hepatic vein catheterization, portal and superior mesenteric artery blood flow velocity, superior mesenteric artery pulsatility index by the echo-Doppler duplex system were recorded at baseline, 1 h after propranolol in the ‘propranolol + octreotide’ group, and in both groups 30 min after octreotide and 30 min after meal. Results At fast, propranolol was more active in decreasing portal pressure (from 16 ± 2.2 to 12.7 ± 3.8 mmHg, − 20%, P< 0.05) as compared to octreotide (from 18.6 ± 4.8 to 16.6 ± 4.3 mmHg, − 11%, P< 0.05). Conversely, octreotide was more active on the mean blood flow velocity of superior mesenteric artery (from 22.8 ± 5 to 19 ± 4.5 cm/s, − 17%;P< 0.05). Octreotide administration in patients receiving β-blockers showed, also, a trend to increase the mesenteric vascular resistances (pulsatility index from 3.14 ± 0.69 to 3.68 ± 1.29, +17%, not significant (NS)) which had not been affected by previous treatment with propranolol. After the meal, a reduction of the expected hyperaemic response occurred in both groups. Conclusions The combined acute haemodynamic effect of this association suggests the possible combination of these two drugs in critical situations, such as variceal bleeding in patients receiving β-blockers. The simultaneous use of echo-Doppler and hepatic vein catheterization permitted us a more complete analysis of the acute haemodynamic events.

Effect of chronic treatment with nadolol plus isosorbide mononitrate on liver blood flow and liver metabolic activity in cirrhosis.

OBJECTIVE To assess the long-term effect of the addition of long-acting nitrates to beta-blockers on liver blood flow and liver metabolic activity in patients with cirrhosis and portal hypertension. METHODS Eleven patients with cirrhosis and portal hypertension were investigated by using hepatic vein catheterization and indocyanine green (ICG) constant infusion on baseline conditions, after 1 month of treatment with nadolol, after 3 months of treatment with nadolol plus isosorbide mononitrate, and (in seven cases) after 1 year of combined treatment. RESULTS The hepatic venous pressure gradient decreased significantly after nadolol, and more so after addition of isosorbide mononitrate. Hepatic blood flow, and ICG intrinsic hepatic clearance did not change significantly, although few cases showed an increase or decrease in either parameter. A significant correlation was found between changes in ICG intrinsic hepatic clearance and in hepatic venous pressure gradient (r = 0.62, P = 0.04). CONCLUSIONS Liver blood flow and liver metabolic activity are not consistently affected by addition of isosorbide mononitrate to nadolol. Substantial decreases in portal pressure may be associated with a decrease in ICG intrinsic hepatic clearance.

ECHO DOPPLER DUPLEX SCANNER AND COLOR IN THE STUDY OF PORTAL HYPERTENSION

In the present state of the art, the Doppler duplex scanner provides much information about portal hypertension and its associated pathology, liver cirrhosis, hepatic malformations, vascular or avascular structures, hepatic transplants, and ascites. Its usefulness for experimental studies, providing new insight into the pathophysiology of this disease, has been proven. It is limited by the subjectivity of the conclusions, and by its poor feasibility in fat patients and those with excessive abdominal gas. However, the noninvasive nature of Doppler and its relative low cost make it a useful first step in the evaluation of portal hypertension.

Hepatic angiodynamic profile in paediatric patients with hereditary haemorrhagic telangiectasia type 1 and type 2

BACKGROUND Liver involvement is a common manifestation of hereditary haemorrhagic telangiectasia (HHT). Although a number of studies have been carried out in adult patients, no study has ever been focused on investigating HHT-related hepatic involvement in paediatric patients. The present study aimed for the first time to systematically estimate the prevalence of HHT-associated liver involvement and to characterize HHT-associated hepatic angiodynamic features in paediatric age. PATIENTS AND METHODS The study was designed as a cross-sectional survey in an HHT paediatric cohort, subclassified as HHT1 and HHT2 according to the mutated gene. The evaluation of the angiodynamic profile was performed by duplex ultrasound examination. Investigation by multi-slice computed tomography (MSCT) or magnetic resonance angiography (MRA) was performed in patients >12 years. RESULTS MSCT/MRA examination disclosed silent hepatic involvement in 7/20 (35.0 %) children, and nodular regenerative hyperplasia in two cases. Diameter of common hepatic artery was significantly larger in HHT2 (0.45 ± 0.15 cm) compared to HHT1 (0.33 ± 0.09, p < 0.01) and control children (0.32 ± 0.08, p < 0.05). None of the patients had clinical manifestations of liver involvement. Angiodynamic profiles were different between paediatric and adult HHT patients. CONCLUSIONS Liver involvement can be detected in paediatric HHT patients, albeit with a lower frequency compared to adults. Paediatric HHT2 children show a higher frequency of liver involvement and a trend to hepatic artery dilation when compared to HHT1 children.

Effect of chronic treatment with nadolol plus isosorbide-5-mononitrate on liver blood flow and liver metabolic activity in cirrhosis

OBJECTIVE To assess the long-term effect of the addition of long-acting nitrates to beta-blockers on liver blood flow and liver metabolic activity in patients with cirrhosis and portal hypertension. METHODS Eleven patients with cirrhosis and portal hypertension were investigated by using hepatic vein catheterization and indocyanine green (ICG) constant infusion on baseline conditions, after 1 month of treatment with nadolol, after 3 months of treatment with nadolol plus isosorbide mononitrate, and (in seven cases) after 1 year of combined treatment. RESULTS The hepatic venous pressure gradient decreased significantly after nadolol, and more so after addition of isosorbide mononitrate. Hepatic blood flow, and ICG intrinsic hepatic clearance did not change significantly, although few cases showed an increase or decrease in either parameter. A significant correlation was found between changes in ICG intrinsic hepatic clearance and in hepatic venous pressure gradient (r = 0.62, P = 0.04). CONCLUSIONS Liver blood flow and liver metabolic activity are not consistently affected by addition of isosorbide mononitrate to nadolol. Substantial decreases in portal pressure may be associated with a decrease in ICG intrinsic hepatic clearance.

Innovation in a traditional setting in Italy: A course on cerebral and peripheral arteriopathy diagnosis for family physicians

A new way of teaching GPs how to diagnose vascular disease is presented by the authors. The workshop for 30 family physicians was based on a more modern educational approach such as the use of television and small group teaching, in addition to traditional methods.The interesting aspects of the methodology used are described. If these methods are considered by themselves none of them will be completely sufficient; on the other hand, all of them have a specific role. On the basis of the success of this experience the authors suggest it as an excellent setting for medical education.