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Biomedical subjects

E Pisi

Publications and source records attributed to E Pisi.

At least 19 recordsLinked to original sources
PubMed2000

Effect of increasing dose of interferon on the evolution of hepatitis C virus 1b quasispecies.

The effects of interferon therapy on hepatitis C virus (HCV) genome are still controversial in terms of biological and clinical significance. Changes in the quasispecies of the hypervariable (HVR) and non-structural 5A (NS5A) regions of HCV 1b were evaluated in nine patients treated with increasing doses of interferon and five untreated controls. HCV quasispecies were analyzed in HVR and NS5A by single-strand conformation polymorphism assay. The HVR quasispecies varied over time both in treated and untreated patients. However, at least one persistent strain was present in all patients. With low doses of interferon, variations in HVR complexity were found in seven of nine patients and in four patients new variants became detectable. A reduction in the heterogeneity of the HVR quasispecies was observed after increase of the interferon dose. In contrast, NS5A profiles remained unmodified in all but three cases in which direct sequencing showed no changes in amino acid sequences of the predominant strain. The results suggest that interferon sensitivity of some HCV strains may be dose dependent. The homogeneity of NS5A pattern populations during treatment suggests that interferon exerts much less pressure on this region.

5' Untranslated Regions↗
PubMed1998

Comparison of serum and liver hepatitis C virus quasispecies in HCV-related hepatocellular carcinoma.

BACKGROUND/AIMS: The hepatitis C virus (HCV) genome consists of quasispecies populations of heterogeneous variants, especially in the hypervariable region. To assess the profiles of viral quasispecies in HCV-related hepatocellular carcinoma, we studied the viral population patterns in serum and liver tissues of 13 HCV-positive patients with hepatocellular carcinoma developed on cirrhotic and non-cirrhotic livers (5 and 8 cases, respectively). METHODS: HCV genome heterogeneity was analyzed by polymerase chain reaction-mediated single-strand conformation polymorphism analysis, which showed multiple DNA bands representing different hypervariable region sequences. RESULTS: The HCV populations were different between tumorous and nontumorous tissues in 3/5 hepatocellular carcinomas with cirrhosis and in 6/8 without cirrhosis. At least one or more than one common band was detected in both compartments in all but one case. No significant differences in the complexity of HCV quasispecies were found in hepatocellular carcinoma with or without underlying cirrhosis. Comparison of the HCV quasispecies profiles in serum and liver tissues showed a different distribution of HCV variants between these two compartments in 6/7 patients. In four cases, both common and compartmentalized sequences were detected, whereas in two cases, both without cirrhosis, the HCV population in serum was completely different from that found in the liver. CONCLUSIONS: These results suggest that the complexity of HCV populations is influenced by the presence of hepatocellular carcinoma rather than by the severity of the underlying chronic liver disease. The different quasispecies patterns found in serum and liver may reflect different biological properties of circulating and intrahepatic HCV particles or the existence of extrahepatic sites of replication.

Aged↗
PubMed1997

Complete eradication of hepatitis C virus after interferon treatment for chronic hepatitis C.

BACKGROUND: Alpha-interferon therapy can lead to a persistent biochemical response, but discordant opinions have been expressed on the definition of sustained response and on the real possibility of complete eradication of hepatitis C virus (HCV). AIMS: To define the clinical, virological and histologic profiles of the patients with sustained response. PATIENTS: Twenty-eight patients with three different biochemical and virological patterns of response to interferon therapy (16 sustained responders, 6 responders with relapse and 6 non responders) were studied for a follow-up period of 36 months. METHODS: HCV-RNA sequences were investigated in serum, peripheral blood mononuclear cells and in liver tissue by means of reverse transcriptase-polymerase chain reaction, targeted to the 5' non coding region. Viral load in serum was quantified by branched-DNA signal amplification. HCV genotypes were evaluated using a line probe assay. RESULTS: All sustained responders showed persistent normal ALT values and loss of serum HCV-RNA during the treatment and in the entire follow-up period. The HCV clearance was also demonstrated in peripheral blood mononuclear cells and in liver tissue. Pre-treatment HCV-RNA quantitation showed that sustained responders had a significantly lower viral load compared to relapsers and non responders (p = 0.005). HCV genotyping showed that patients infected by genotypes 2a, 3a were more likely to achieve a sustained response. Interestingly, a prolonged response was also observed in the only three patients with pre-treatment detectable viral load infected by genotype 3a and in patients with genotype 1b and low viraemia levels. To assess the histologic outcome following HCV eradication, all sustained responders underwent a second liver biopsy in the follow-up period (6-18 months). Periportal necrosis and portal inflammation were significantly improved. CONCLUSIONS: Our results suggest that persistent loss of HCV-RNA in serum, peripheral blood mononuclear cells and liver as well as histologic improvement are consistent with the complete HCV eradication even from intracellular compartments and from potential extra-hepatic sites of viral persistence. Moreover, pre-treatment viral load, HCV infecting genotypes and histologic features may influence the clinical outcome of hepatitis C and the response to interferon therapy.

Adult↗
PubMed1996

Efficacy of a surveillance program for early detection of hepatocellular carcinoma.

BACKGROUND: Contrasting data have so far been reported on the utility and efficacy of screening patients with cirrhosis for early detection of hepatocellular carcinoma (HCC). The goal of this study was to evaluate the efficacy of a regular ultrasonographic and laboratory follow-up for the early detection of small HCC, and to identify parameters correlated with a higher risk of developing HCC. METHODS: One hundred and sixty-four consecutive patients with liver cirrhosis living in Emilia Romagna, Italy, were enrolled in the period 1989-1991. All patients underwent clinical, biochemical, and ultrasonographic evaluations at entry and at 3- and 6-month intervals during follow-up. RESULTS: By April 1995, 34 patients had developed HCC. In 76% of the patients, ultrasonography identified HCC when it was still single and small (< 4 cm). At discriminant, logistic regression and univariate analyses, sex and the entry concentration of alkaline phosphatase, alpha-fetoprotein, gamma-glutamyl transpeptidase, and albumin were associated with a higher risk of developing HCC, whereas at multivariate analysis (Cox's model), only sex and the entry concentration of alkaline phosphatase, albumin, and alpha-fetoprotein were independently and significantly related to the appearance of HCC. CONCLUSIONS: A regular ultrasonographic follow-up, timed at 3- to 6-month intervals according to the risk of HCC development in patients with cirrhosis, allows the detection of liver carcinoma at an early stage in a high proportion of patients, possibly improving the prognosis of the disease.

Adult↗
PubMed1996

Transdermal nitroglycerin in cirrhosis. A 24-hour echo-Doppler study of splanchnic hemodynamics.

BACKGROUND/AIMS: The present study was aimed to evaluate the 24-hour effect of transdermal nitroglycerin on splanchnic hemodynamics in cirrhotic patients. METHODS: Hemodynamic parameters (blood velocity and resistance indexes) were determined by means of pulsed echo-Doppler, a non-invasive method which proved to be useful to evaluate the effects of drugs on splanchnic vessels. Nine patients with biopsy-proven liver cirrhosis were studied. They were kept on a standard diet divided into 3 meals served at 8, 12 a.m. and 6 p.m. Echo-Doppler measurements were determined for 2 consecutive days at 7, 8, 9, 12 a.m, 1, 3, 6, 7, 9, 12 p.m. and again at 7 a.m. A transdermal nitroglycerin tape, capable of releasing 15 mg of the drug in 24 h, was applied to the skin of the chest at 7 a.m. of the second day. RESULTS: After nitroglycerin mean portal blood velocity and flow significantly decreased by 18 and 22%. Similarly superior mesenteric artery velocity decreased, while resistance indexes increased. ANOVA analysis showed a significant effect of the drug on superior mesenteric artery and portal flow, while the effect on hepatic artery flow and renal indexes were low. CONCLUSIONS: This study shows that nitroglycerin, given as transdermal long-acting system, significantly influences portal hemodynamics in liver cirrhosis. Its use, favoured by easy administration, may be proposed for long-term clinical studies to test its efficacy in preventing gastrointestinal bleeding.

Administration, Cutaneous↗
PubMed1996

Evaluation of a new endoscopic index to predict first bleeding from the upper gastrointestinal tract in patients with cirrhosis.

The aim of this study was to prospectively evaluate the usefulness of the Italian Liver Cirrhosis Project (ILCP) classification of esophageal varices, together with the gastric features of portal hypertension, in predicting the first upper gastrointestinal bleeding in cirrhosis. The efficiency of these endoscopic parameters in predicting bleeding was also compared with the efficiency of the North Italian Endoscopic Club (NIEC) index. Three hundred forty-four cirrhotic patients with esophageal varices but without any previous bleeding were enrolled in the study. The following endoscopic parameters of esophageal varices were recorded: location, size, occupancy, blue tone, and red color signs. Gastric varices were graded as absent or present, while congestive gastropathy was considered as absent, mild to moderate, or severe. All patients were followed until the first upper gastrointestinal bleeding and/or death, or for at least 24 months. No patient received any treatment to prevent bleeding. Sixty-five patients bled from the upper gastrointestinal tract during the study. Univariate analysis showed that all endoscopic parameters were predictors of bleeding. According to multivariate analysis (Cox's model), size, gastric varices and congestive gastropathy were the only independent predictors of bleeding, and the following prognostic index (PI) was developed: PI = (size x 0.0395) + (congestive gastropathy x 0.878) + (gastric varices x 0.705). This index, which was validated using a split-sample technique, and which appears to be superior to the NIEC index in predicting bleeding, may be useful in decision making for primary prophylaxis.

Adult↗
PubMed1995

HCV-associated liver cancer without cirrhosis.

Chronic infection with hepatitis C virus (HCV) is regarded as a risk factor for hepatocellular cancer, mostly in patients with liver cirrhosis. We looked for HCV genomes in the livers of patients with hepatocellular cancer who did not have cirrhosis to see whether HCV was directly oncogenic. Cancerous and non-cancerous liver tissue, and serum samples from 19 patients negative for hepatitis B surface antigen were analysed by polymerase chain reaction for the presence of HCV genome, HCV replication, HCV genotyping, and HBV genome. 13 of 19 patients were HCV RNA-positive in cancerous and non-cancerous liver tissue; 8 of 17 tested were anti-HCV positive. Among the 13 HCV RNA-positive patients, 11 had genotype 1b and 2 had genotype 2a. 7 of 13 serum samples were HCV RNA positive. 7 of 19 patients were HBV DNA positive in cancerous and non-cancerous liver tissue, 5 of them anti-HBc positive. 4 patients were both HCV RNA and HBV DNA positive and 3 were both HCV RNA and HBV DNA negative. Our results provide evidence for the association of HCV, mostly genotype 1b, with hepatocellular cancer without the intermediate step of cirrhosis.

Adult↗
PubMed1995

Structure and expression of the cyclin A gene in human primary liver cancer. Correlation with flow cytometric parameters.

BACKGROUND/AIMS: The cyclin A gene plays an important role in both the S and G2-M phases of the cell cycle, and has been identified at a site of hepatitis B virus DNA integration in a human liver cancer. We analyzed tumorous and non-tumorous samples from patients with primary liver cancer to determine whether a) the cyclin A gene is rearranged in liver tumors and b) the cyclin A transcript level correlates with the percentage of proliferating cells. METHODS: Samples from 43 patients were analyzed by Southern blot. Cyclin A RNA accumulation was evaluated in 18 cases by slot blot and correlated with the percentage of cells in S plus G2-M phases defined by flow cytometry. RESULTS: No rearrangement of the cyclin A gene was found in tumorous compared to non-tumorous tissue. A very strong positive correlation was found between the cyclin A RNA level and the cumulative percentage of cells in S plus G2-M phases (r = 0.99; p < 0.0001). CONCLUSIONS: This in vivo study shows that the expression of cyclin A RNA correlates with the percentage of proliferating cells in primary liver cancer. Thus, cyclin A is a new potential liver tumor cell proliferation index.

Blotting, Southern↗
PubMed1995

Functional hepatic flow and Doppler-assessed total hepatic flow in control subjects and in patients with cirrhosis.

Functional hepatic flow and total hepatic flow were determined by non-invasive techniques in 32 patients with cirrhosis and in 32 paired control subjects. Functional hepatic flow was measured by the hepatic clearance of D-sorbitol, while total hepatic flow was determined by pulsed echo-Doppler, as the sum of portal and hepatic arterial blood flow. Functional hepatic flow was significantly reduced in patients with cirrhosis (927 +/- 314 vs. 1287 +/- 315; p < 0.0001), while total hepatic flow was slightly increased (1511 +/- 540 vs. 1261 +/- 321 in controls; p = 0.028). In control subjects functional hepatic flow significantly correlated with total hepatic flow (r = 0.823; p < 0.001), while no correlation was observed in cirrhosis. Functional hepatic flow and the difference between total hepatic flow and functional hepatic flow significantly correlated with the Child-Pugh score in patients with cirrhosis. The data obtained in control subjects support the measurement of functional hepatic flow and total hepatic flow by non-invasive techniques. The finding that in cirrhosis functional hepatic flow is significantly decreased, while Doppler-assessed total hepatic flow is preserved or even increased, confirms that a relevant part of blood flowing through the liver is diverted by intrahepatic shunts. The simultaneous assessment of these two parameters by non-invasive techniques may be proposed as a reliable tool for the study of functional shunting of cirrhosis.

Adult↗
PubMed1995

Physical examination of the liver: is it still worth it?

OBJECTIVES: The aim of this study was to evaluate the actual role of physical examination of the liver in normal subjects and in cirrhotic patients. METHODS: One hundred healthy subjects and 100 patients with liver cirrhosis underwent a physical and an ultrasonographic evaluation of the liver by independent operators. Physical examination was performed by means of percussion and palpation to determine total liver span, liver span below the costal margin, and liver consistency. Total liver span, liver span below the costal margin, and liver volume were also determined by means of ultrasonography. RESULTS: The agreement between physical and ultrasonographic assessment of the liver span below the costal margin was poor in controls (chance corrected agreement index = 0.13) and excellent in patients (chance corrected agreement index = 0.93). Physical and ultrasonographic total liver span were correlated in patients with cirrhosis (r = 0.592) but not in controls (r = 0.205). Echo-measured liver span significantly correlated with the actual volume of the organ in both groups, whereas physical liver span significantly correlated with liver volume in cirrhosis but not in controls. The difference between actual liver volume and the value predicted by liver span was large. The cirrhotic liver was slightly reduced in size in comparison with that of healthy subjects and differed by an increase in consistency and a thickened edge. CONCLUSIONS: The bedside examination of the liver does not provide any accurate information regarding the actual volume of the organ. Its major role remains to define the characteristics of lower edge, mainly consistency, which may help in clinical diagnosis. Liver volume proved to predict prognosis in patients with cirrhosis, but its measurement needs quantitative, reproducible methods, which can be obtained only by imaging techniques.

Case-Control Studies↗
PubMed1994

A new risk of occupational disease: allergic asthma and rhinoconjunctivitis in persons working with beneficial arthropods. Preliminary data.

For some years, biological pest control has been re-evaluated as an alternative to the indiscriminate use of pesticides. The number of "bio-factories" in Europe has been constantly increasing and today more than 100 technicians work in mass rearing of arthropods. Seven cases of asthma and allergic rhinitis are reported in 13 workers engaged in the production of beneficial arthropods. The subjects suffered from attacks of asthma and rhinitis when they came into contact with eggs and scales or waste of Chrysoperla carnea, Leptinotarsa decemlineata, Ostrinia nubilalis and Ephestia kuehniella. These attacks occurred after an average exposure period of 18 months. A RAST test, prepared by Lofarma, was carried out on subjects' serum against the above-mentioned allergens and was positive in all symptomatic subjects (7 of 13) and negative in the others. This demonstrates IgE direct sensitization mediated by complete antigens.

Adult↗
PubMed1994

Prognostic significance of diabetes in patients with cirrhosis.

Alterations in carbohydrate metabolism are frequently observed in cirrhosis, and approximately 15% to 30% of patients have overt diabetes. In a retrospective and prospective study in cirrhosis, we analyzed the prognostic significance of diabetes, which was defined as the presence of hyperglycemia and overt glycosuria that in most cases required dietary restrictions or active treatment. The clinical records of all patients with cirrhosis admitted to our department for the period 1980 to 1985 were reviewed in 1985 and 1986, and surviving patients were prospectively followed up until December 1991. Final status could be obtained in 354 (98 with diabetes) of 382 eligible patients; 110 were alive at the end of follow-up. Prognostic factors were identified by Kaplan-Meier analysis, followed by Cox's stepwise regression. The model identified, in sequence, albumin, ascites, age, encephalopathy, bilirubin, diabetes, and platelets as prognostic factors. The larger mortality rate in patients with diabetes was not due to complications of diabetes but to an increased risk of hepatocellular failure. Diabetes was no longer a risk factor as a covariate in a subgroup of 271 patients when varices were added but was again significant when patients who died of gastrointestinal bleeding were excluded. The presence of diabetes, clinically detectable and often requiring adequate treatment, is a risk factor for long-term survival in cirrhosis.

Adolescent↗
PubMed1994

Different in situ expression of insulin-like growth factor type II in hepatocellular carcinoma. An in situ hybridization and immunohistochemical study.

Reexpression of the insulin-like growth factor type II (IGF-II) gene has recently been described in hepatocellular carcinoma (HCC). In this study, we used a nonisotopic in situ hybridization method to analyze the expression of IGF-II mRNA in a series of 28 HCCs arising on cirrhotic and noncirrhotic livers. An immunohistochemical method was used to detect IGF-II peptide. Hepatitis B virus (HBV) status and the histological differentiation degree were also evaluated. Increased expression of IGF-II mRNA was found in 4 of 28 HCCs, and 7 of 17 cirrhotic patients showed IGF-II mRNA in the cirrhotic nodules surrounding the HCC. A slightly higher rate of positivity for IGF-II mRNA was found in the HBV-negative patients than in HBV-positive ones. Positive immunostaining for the IGF-II peptide in the HCC and/or in surrounding cirrhotic nodules was found in 10 of 28 cases. The normal hepatocytes of the noncirrhotic patients were always negative for IGF-II peptide and mRNA. The similarities between our results and those from experimental models in woodchucks seem to support the concept that heterogeneous phenotypic groups could exist in human HCCs.

Carcinoma, Hepatocellular↗
PubMed1994

Kinetics of hepatic amino-nitrogen conversion in ageing man.

Previous studies have shown that hepatic function, quantitatively measured by dynamic liver function tests, progressively declines with ageing. Urea synthesis is a specific process taking place in the liver; a reduced urea synthesis in response to a protein-rich metal has previously been demonstrated in the elderly, but the process has never been standardized in relation to amino acid supply. We measured the hepatic conversion of alpha-amino nitrogen into urea nitrogen in response to alanine infusion in 32 subjects, with normal routine liver and renal function tests and without evidence of previous hepatic disorders, belonging to three different age-groups (< or = 55 years, 56-70, > or = 71). The functional hepatic nitrogen clearance was reduced on average by 20% in subjects aged 56-70 years, and by 30% in subjects over 70 years old in comparison to the age-group under 55 years (ANOVA: P = 0.0001), and significantly correlated with age (r = -0.684). No sex differences were observed on the effects of age on hepatic clearance. Also, liver volume, measured by ultrasonography, was reduced with advancing age, but the age-related decrease in hepatic nitrogen conversion was not primarily dependent on decreased liver volume. The measurement of functional hepatic nitrogen clearance has already been validated as a quantitative liver function test in clinical hepatology. In keeping with previous studies, the age-related decline in hepatic nitrogen conversion points to a decreased functional capacity of the ageing hepatic parenchyma.

Aged↗
PubMed1994

[Ultrasonographic evaluation of gallbladder and gastric emptying after ingestion of water with various saline compositions].

OBJECTIVE: Evaluation of gallbladder and gastric emptying after ingestion of a saline enriched water ("Acqua Santa" di Chianciano) in comparison with a commercial oligomineral water. STUDY DESIGN: A 40-minute blind prospective study. LOCATION: The study was performed at the Terme of Chianciano (Siena) for subjects of group A and at the Institute of Clinica Medica Generale and Terapia Medica of the University of Bologna for subjects of group B. PATIENTS OR PARTICIPANTS: Two groups of healthy subjects were studied. Each group consisted of 12 subjects without gallbladder disease. EXPERIMENTAL PROTOCOL: Fasting subjects of group A ingested alternatively, for two consecutive mornings, 400 ml of the saline enriched water at the natural temperature of 33 degrees C or 400 ml of oligomineral water warmed to the same temperature. Subjects of group B ingested the same waters at 18 degrees C. METHODS: Gastric and gallbladder emptying were evaluated, after ingestion of the different waters, by means of ultrasonography. RESULTS: In both groups gallbladder emptying was significantly higher after ingestion of the saline enriched water. On the other hand gastric emptying was similar with both waters. CONCLUSIONS: This study demonstrated that saline enriched water determines a greater emptying of the gallbladder in comparison with an oligomineral water. This effects is not related to gastric emptying but rather it is due to a higher concentration of saline components and thus to their possible effect on gallbladder motility.

Adult↗
PubMed1993

Prognostic significance of portal hemodynamics in patients with compensated cirrhosis.

The prognostic value of portal hemodynamics, measured by pulsed echo-Doppler, was prospectively evaluated, together with clinical, biochemical and endoscopic parameters, in a series of 50 consecutive patients with compensated cirrhosis. After a mean follow-up of 6 years, 25 patients had died, all from complications of liver disease. Among conventional variables, the step-wise Cox model showed that only the Child-Pugh score independently predicted death (chi 2 = 18.66; p < 0.001). When hemodynamic parameters were added to the Child-Pugh score in the same model, portal blood velocity was shown to add prognostic significance (improvement in chi 2 = 14.06; p = 0.0002; Wald test). The present study shows that a portal blood velocity below the lower limit of controls (10 cm/s) characterizes patients with shorter survival, and suggests that this non-invasive parameter should be associated to the Child-Pugh score in the evaluation of patients with cirrhosis.

Adult↗
PubMed1993

Vegetable versus animal protein diet in cirrhotic patients with chronic encephalopathy. A randomized cross-over comparison.

In a randomized cross-over comparison, the effects of a mainly vegetable protein diet were compared with an animal protein diet in eight patients with cirrhosis and chronic permanent encephalopathy, under optimum lactulose therapy. After a run-in period, patients were fed two equi-caloric, equi-nitrogenous diets for 7 days (71 g total proteins), containing either 50 g protein of animal origin or 50 g vegetable proteins. In the last 3 days of each period, nitrogen balance was significantly better during the vegetable protein diet (+0.2 (SD 1.4) g vs. -1.7 (2.4); P < 0.01), the difference being entirely due to a reduced urinary nitrogen excretion. Average daytime integrated blood glucose was slightly higher during vegetable proteins, whereas insulin, plasma amino acids and ammonia were lower. The clinical grading of encephalopathy improved slightly on vegetable proteins, and psychometric tests improved significantly, but remained grossly abnormal. Compliance to dietary manipulation was good. The data prove that a mainly vegetable protein diet is worthwhile in cirrhotic patients with chronic encephalopathy under optimum lactulose therapy. Improved nitrogen balance may be related to more effective nitrogen use for protein synthesis, probably due to blunted hormonal response, and largely outweighs the effects on encephalopathy.

Aged↗