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Biomedical subjects

N Dioguardi

Publications and source records attributed to N Dioguardi.

At least 19 recordsLinked to original sources

Hepatocellular carcinoma in Italian patients with cirrhosis.

BACKGROUND AND METHODS: Patients with cirrhosis of the liver are recognized as being at risk for hepatocellular carcinoma. The magnitude of the risk, the natural history of this disease, and the possibilities for detecting potentially curable tumors in patients in the Western world are unknown. To address these questions, we examined 447 Italian patients with well-compensated cirrhosis (which was of viral origin in 62 percent of them) from 1985 through 1990, performing serum alpha-fetoprotein assays and real-time ultrasonography every 3 to 12 months. RESULTS: Hepatocellular carcinoma was found in 30 patients (7 percent) at base line and in another 29 patients (7 percent of 417 patients free of tumor at base line) during follow-up periods averaging 33 months (range, 1 to 48). The cumulative hazard of the development of hepatocellular carcinoma during follow-up was higher among patients with persistently elevated serum alpha-fetoprotein levels (12 with tumors among 42 with such levels) than among those with fluctuating levels (11 among 82) or those with consistently normal levels (6 among 255). Only 17 patients had potentially operable tumors. The proportion of potentially operable tumors among those detected during follow-up was significantly lower than the proportion at enrollment (4 of 29 vs. 13 of 30, P = 0.027). The survival at one year of the 12 patients who underwent surgery was 67 percent, and the tumor-recurrence rate was 60 percent. Outcome was not appreciably different for the five patients who refused surgery. CONCLUSIONS: In the West, as in Asia, patients with cirrhosis of the liver are at substantial risk for hepatocellular carcinoma, with a yearly incidence rate of 3 percent. Our screening program did not appreciably increase the rate of detection of potentially curable tumors.

Adult

Modeling of biological and medical systems: a systemic strategy.

A strategy in the frame of General System Theory is proposed for the study of biological systems for medical purposes. Its definition and use requires in each experiment the collaboration between physician and system scientists and hence the definition of a common language, by which the real system under study is described. The strategy is based on three intermingled steps: first an ingenuous model is proposed, gathering all the medical knowledge about the studied system, organized within an informal frame derived from the state space approach. Next, a functional model is derived, enlightening the organization of the relations in the medical model. Finally, this organization is formalized by the most suitable algebraic tools, which are thereafter translated into APL programs. This last version is used for simulation, which is exploited not only as a tool to describe and make provisions on the dynamics of the models, but also to deepen and improve the knowledge about the observed system.

Computer Simulation

Atrial natriuretic factor in cirrhotic patients with tense ascites. Effect of large-volume paracentesis.

The plasma levels of atrial natriuretic factor in liver cirrhosis can be affected by various factors, such as ascites, renal function, use of diuretics drugs and dietary sodium intake. Moreover, the influence of high intra-abdominal pressure on cardiac atrial natriuretic factor release in patients with tense ascites has not been investigated. The aim of the present study was to evaluate the circulating levels of atrial natriuretic factor and their relationships to plasma renin activity, aldosterone concentration, and urinary sodium excretion in 45 cirrhotic patients divided into 4 groups: (a) cirrhotics without ascites; (b) nonazotemic cirrhotics with ascites; (c) cirrhotics with ascites and functional renal failure; and (d) cirrhotics with ascites taking diuretics. In some patients with tense ascites, atrial natriuretic factor was also measured after rapid abdominal relaxation by large volume paracentesis. Plasma levels of atrial natriuretic factor obtained in 13 healthy control subjects after 5 days on a 40-50 mEq sodium daily intake were 22.8 +/- 3.3 pg/ml. Mean plasma atrial natriuretic factor levels were normal in patients without ascites (35.1 +/- 11.4 pg/ml) and in those with ascites taking diuretics (27 +/- 9.2 pg/ml), but elevated in patients with ascites not taking diuretics (59.6 +/- 12 pg/ml) and in those with ascites and functional renal failure (58.5 +/- 16.6 pg/ml). These data show that plasma atrial natriuretic factor levels are elevated only in cirrhotic patients who are ascitic and not taking diuretics. In these patients atrial natriuretic factor levels were directly correlated with urinary sodium excretion, even though sodium balance was positive. This could be the consequence of the contrasting effects of antinatriuretic factors, as suggested by the inverse relationships between atrial natriuretic factor and urinary sodium on the one hand and plasma renin activity and plasma aldosterone concentration on the other. Twenty-six patients with tense ascites (12 taking diuretics and 14 not) were treated with rapid large-volume paracentesis (6500 +/- 330 ml of ascitic fluid removed in 168 +/- 16 min). At the end of the procedure, plasma atrial natriuretic factor levels had increased in all patients (from 45.5 +/- 10.1 to 100 +/- 17 pg/ml), whereas plasma renin activity and plasma aldosterone concentration had decreased (from 10.3 +/- 1.6 to 7 +/- 1.3 ng/ml/h, and 1160 +/- 197 to 781 +/- 155 pg/ml, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Aldosterone

Prevalence of antibodies to hepatitis C virus in Italian patients with hepatocellular carcinoma.

A sensitive radioimmunoassay was used to detect antibodies to hepatitis C virus (HCV) in patients with hepatocellular carcinoma and chronic hepatitis. HCV antibodies (anti-HCV) were detected in 86 of 132 patients with hepatocellular carcinoma with no relation to the presence or absence of hepatitis B surface antigen (HBsAg). The prevalence of anti-HCV was also high in patients with diseases thought to predispose to hepatocellular carcinoma, such as non-A, non-B chronic hepatitis and cirrhosis (74%). In HBsAg-negative patients with hepatocellular carcinoma the prevalence of anti-HCV was lower than that in patients with non-A, non-B chronic hepatitis (16% vs 55%); the prevalence of serum antibodies to hepatitis B core antigen (anti-HBc), a marker of hepatitis B virus infection, was 70% and 28%, respectively. In HBsAg-negative patients with hepatocellular carcinoma, anti-HCV and anti-HBc occurred together nearly three times as often as in patients with chronic hepatitis (54% vs 19%). These data indicate that, in Italy, HCV is an important factor associated with hepatocellular carcinoma and non-A, non-B chronic hepatitis.

Adult

Beta-blockade prevents recurrent gastrointestinal bleeding in well-compensated patients with alcoholic cirrhosis: a multicenter randomized controlled trial.

To assess the efficacy of beta-blockers in preventing rebleeding in selected cirrhotic patients and to compare the tolerance, safety and patient compliance of a selective and a nonselective beta-blocker, 94 patients were randomly assigned to propranolol (32 patients), atenolol (32 patients) or placebo (30 patients). Randomization was made at least 15 days after the bleeding episode. Propranolol was given orally at increasing doses until the resting pulse rate was reduced by approximately 25%. Atenolol was given at a fixed dose of 100 mg per day. Patients were followed up for a mean of 357 days. Rebleeding occurred in 14 patients in the placebo group, 10 in the atenolol group and eight in the propranolol group. The incidence of rebleeding was significantly lower in patients receiving propranolol than in those on placebo (propranolol vs. placebo: p = 0.01, logrank test). Atenolol was less effective than propranolol (atenolol vs. placebo: p = 0.065, logrank test). Bleeding-free survival was better for patients on active drugs than for those on placebo (propranolol vs. placebo = p = 0.01, atenolol vs. placebo: p = 0.05, logrank test). Retrospective analysis revealed that, whatever the type of treatment, abstinence from alcohol was crucial in preventing rebleeding. We conclude that beta-blocker treatment is effective in preventing rebleeding from esophageal varices in carefully selected alcoholic cirrhotic patients who survive at least 2 weeks after acute variceal hemorrhage and stop drinking.

Actuarial Analysis

Serum total lipids, lipoproteins cholesterol, apoproteins A and B in cardiovascular disease.

Serum total lipids and lipoproteins cholesterol were determined in 33 survivors of myocardial infarction (MI) and in 75 subjects with peripheral vascular disease (PVD). Measurements were also made by a quantitative immunological assay of Apoprotein A (Apo A) and B (Apo B). Apo A levels were significantly lower in cases than in controls. In those cases with low levels of Apo A, high density lipoprotein has a higher cholesterol content as compared with controls. A negative correlation between high density lipoprotein cholesterol and low density lipoprotein cholesterol was found in controls and PVD subjects. The findings suggest that Apo A is associated to MI and PVD and its quantitative determination is predictive of cardiovascular disease.

Adult

[Behavior of total lipids, cholesterol, lipoproteins and apolipoprotein A in the blood of subjects with acute hepatitis and chronic hepatopathy].

Serum total lipids, lipoprotein cholesterol, apolipoprotein A (Apo A) and liver function parameters have been investigated in patients with acute viral hepatitis and chronic liver disease. Hypertriglyceridaemia, absence of alpha and pre beta bands on the lipoprotein electrophoresis pattern, low level of Apo A, presence of abnormal lipoproteins (beta-VLDL and beta2-LP) were observed in the early phase of acute hepatitis. A positive correlation was found between Apo A and triglyceride bile acids, log total bilirubin, log SGPT. Lipoprotein abnormalities are probably due to low lecitin-cholesterol aciltransferasi activity. The reappearance of alpha lipoprotein and the increase of Apo A are sensitive indices of improvement of liver function. In chronic liver disease the levels of cholesterol and Apo A correlate with changes in the hepatocellular function.

Acute Disease

Serum total lipids, lipoprotein cholesterol, and apolipoprotein A in acute viral hepatitis and chronic liver disease.

Serum total lipids, lipoprotein cholesterol, apolipoprotein A (Apo A), and liver function tests have been investigated in patients with acute viral hepatitis and chronic liver disease. Hypertriglyceridaemia, absence of alpha and pre beta bands on the lipoprotein electrophoresis pattern, low level of Apo A, and presence of abnormal lipoproteins (beta-VLDL and beta2-LP) were observed in the early phase of acute hepatitis. A positive correlation was found between Apo A and high-density lipoprotein cholesterol, and a negative one between Apo A and triglyceride, bile acids, total bilirubin, and serum alanine aminotransferase. Lipoprotein abnormalities found in the early phase of acute hepatitis are probably due to low lecithin-cholesterol acyltransferase activity. The reappearance of alpha lipoprotein and the increase of Apo A are sensitive indices of improvement of liver function. In chronic liver disease low levels of cholesterol and Apo A indicate the severity of liver cell injury.

Apolipoproteins

Correction of abnormal coagulation in chronic liver disease by combined use of fresh-frozen plasma and prothrombin complex concentrates.

The effect on abnormal coagulation tests of infusions of fresh-frozen plasma (F.F.P), prothrombin complex concentrates, and a combination of these treatments was compared in 30 patients with chronic liver disease undergoing needle biopsy. A single dose of F.F.P. (12 ml/kg body-weight) was found to be the least effective therapeutic regimen. The concentrate containing factors II, IX, and X was also not adequate, but the additional administration of factor-VII concentrate corrected the prothrombin-time (P.T.) and "Normotest" (N.T.) in most patients. However, this regimen did not correct the prolonged kaolin activated partial thromboplastin-time (K.P.T.T.). The results of tests for exploring both the extrinsic (P.T. and N.T.) and intrinsic (K.P.T.T.) coagulation systems only became normal after the combined administration of a lower dose of F.F.P. (8 ml/kg body-weight) and of both concentrates (12 units/ml). There was no clinical or laboratory evidence of thrombotic complications. No patient developed acute hepatitis or hepatitis-B surface antigen in the twelve months after biopsy. These results indicate that prothrombin-complex concentrates in combination with F.F.P. may therefore be used to allow liver biopsy to be performed safely in patients presenting with severe coagulation defects.

Biopsy

[Controlled clinical trial of 2-mercapto-propionyl-glycine in chronic hepatopathies].

A controlled clinical trial comparing 2-Mercapto-Priopionyl-Glycine (2-MPG) plus B12 vitamin with B12 vitamin alone in chronic liver disease has been conducted in seven hospitals in Italy. Patients were divided into two groups on the basis of liver histology; group I included 26 patients showing histological evidence for chronic persistent hepatitis (C.P.H.) (according to De Groote et al.) whereas group II consisted of 54 patients with chronic aggressive hepatitis (C.A.H.) or compensated liver cirrhosis. Patients of each group were randomly allocated to 2-MPG plus B12 vitamin, or to placebo plus B12 vitamin, in a double-blind way. The drug (or placebo) was diluted in 500 ml of 10% Levulose, and administered intravenously; 1000 gamma of B12 vitamin were added to each bottle. Patients in the 2-MPG group received 2.5 gms of the drug daily; the treatment lasted for 30 days. The following parameters were checked in all patients on admission, and repeated at the end of treatment: Serum bilirubin, serum Cholesterol, A.P., BSP retention, Prothrombin time, S-GOT, S-GPT, Gamma-GT, Total serum Protein, serum electrophoresis, Immunoglobulins. Patients given 2-MPG showed significant decreases of serum transaminases, and improvement of BSP retention.

Amino Acids, Sulfur

Rosette inhibition test in chronic liver disease.

A role has recently been assigned to cell-mediated immunity in chronic liver diseases in addition to the well-known alterations of humoral immunity. We now report the results of the rosette inhibition test for the evaluation of T-lymphocyte "sensitization" in patients with different chronic liver disorders. A cell-mediated immune reaction was found in 81% of patients with chronic active hepatitis and in 71% with primary biliary cirrhosis, whereas patients with chronic persistent hepatitis showed no reaction. The correlation with the incidence of hepatitis B antigen showed that T-lymphocyte sensitization was more frequent in the group of HB-positive patients. Finally, improvement of the test was observed in four out of nine patients given immunosuppressive treatment.

B-Lymphocytes

[Double-blind polycentric study of the action of S-adenosylmethionine in hepatic cirrhosis].

Two comparable groups of patients with hepatic cirrhosis of different genesis in a compensation phase have been treated for 30 days with S-adenosylmethionine and vitamine B-12 (28 cases) or with vitamine B-12 alone (25 cases). The drugs were given by slow intravenous route at the daily dose of 150 mg of SAMe and 2000 gamma of vit. B-12 or of 2000 gamma of vit. B-12 alone, in two adminstrations. An evaluation of the results was carried out mostly on the laboratory data testing the liver function. Only the group of patients who had received SAMe showed significant modifications of all the parameters considered. This is confirming SAMe ability to restore hepatocyte activity bringing also to normal the protein synthesis.

Aged

[Bile secretion].

The canaliculus is the primary site for the formation of bile. Here, active secretion of bile acids creates an osmotic gradient between bile and blood, crossed passively by water and solutes. Numerous experimental data point to the existence of a canalicular bile fraction that is independent of the active transport of bile acids and related to active sodium secretion. The bile ducts are not mere conduits for the passage of bile, but can also change its volume and composition by means of both absorption and secretion. Nervous, vascular, hormonal and pharmacological factors serve to modify bile secretion. In most cases, however, their mechanism of action is virtually unknown.

Adenosine Triphosphate

[Incidence of HBsAg in persons living with HBsAg carriers].

The prevalence of HBsAg was studied, by Counterelectrophoresis and Radioimmunoassay, in 232 household contacts of 65 HBsAg carriers. The overall incidence of HBsAg in household contacts was 14,65%, as compared with the generally accepted figure of about 1% in the general population in Italy. As far as the prevalence of HBsAg and abnormal liver function tests is concerned, no differences were found between contacts of carriers with Chronic Active Liver Disease and contacts of asymptomatic carriers. The prevalence of HBsAg was similar in spouses (13,5%) and in blood relatives (15,3%) of carriers. It is concluded that: 1) Household contacts of HBsAg carriers are at higher risk of acquiring HBsAg infection than the general population. 2) Such risk is not increased by the presence of Chronic Active Liver Disease in the index cases. 3) Further studies are required in order to clarify the relative roles of environmental and genetic factors as determinants of HBsAg transmission.

Adult

A computer-assisted study of macrophage behavior in HBV and nAnB related infectious chronic active hepatitis.

Activated intralobular macrophages were quantified as their lysozyme contents in liver biopsies from patients with chronic HBV and nAnB active hepatitis, and subjects with no evident liver histological damage. There were more macrophages (0.62 +/- 0.06/2,500 mu 2) with a larger area (20.36 +/- 0.87 mu 2) in HBV-related chronic active hepatitis than in controls (0.21 +/- 0.04/2,500 mu 2 and 16.01 +/- 1.48 mu 2), whereas in nAnB chronic active hepatitis their numbers were similar to that in the controls (0.22 +/- 0.03/2,500 mu 2) and their area was smaller (11.68 +/- 0.79 mu 2).

Biopsy