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Biomedical subjects

A Gatta

Publications and source records attributed to A Gatta.

At least 19 recordsLinked to original sources
PubMed2006

Peripheral neurotoxicity of pegylated interferon alpha: a prospective study in patients with HCV.

OBJECTIVE: To assess whether pegylated interferon alpha (PEG-IFNalpha) may induce peripheral neuropathy or antibodies to peripheral nerve antigens in patients with hepatitis C virus (HCV) infection. METHODS: We studied 52 patients with HCV (38 men, 14 women; mean age 44.6 +/- 10.6 years) treated with IFNalpha. Before therapy (T(0)), patients underwent quantitative viral RNA determination, HCV genotype analysis, and neurologic and electrophysiologic evaluation. At the end (T(1)) and after therapy (T(2)), patients were neurologically and electrophysiologically re-evaluated. Antibodies to gangliosides and sulfatides were assayed by ELISA at T(0) and T(1). Twenty-three patients with HCV with comparable age, viral load, and genotype, not treated with IFNalpha, were studied as controls. RESULTS: Seven patients (six in IFNalpha, one control) had peripheral neuropathy at recruitment. No significant differences in the electrophysiologic measures were detected between T(0) and T(1) (repeated-measures analysis of variance [ANOVA]) in any of the 52 patients or in those with neuropathy at T(0). No changes were found at T(2), independent of the viral response to treatment. Two patients, one with neuropathy, had antiganglioside antibodies at recruitment. Two patients, one not treated with IFNalpha, developed low antibody titers during follow-up, without symptoms or signs of neuropathy. CONCLUSIONS: Pegylated interferon alpha therapy was not associated with the occurrence (or worsening) of peripheral neuropathy or antibodies to peripheral nerve antigens in patients with hepatitis C virus.

Adolescent↗
PubMed2006

The EEG assessment of low-grade hepatic encephalopathy: comparison of an artificial neural network-expert system (ANNES) based evaluation with visual EEG readings and EEG spectral analysis.

OBJECTIVE: The EEG provides an objective staging of hepatic encephalopathy (HE), but its interpretation may be biased by inter-observer variability. This study aims at comparing an entirely automatic EEG classification of HE based on an artificial neural network-expert system procedure (ANNES) with visual and spectral analysis based EEG classifications. METHODS: Two hundred and thirty-eight consecutive cirrhotic patients underwent closed-eye EEG. They were followed up for up to one-year to detect bouts of overt HE and death. The EEG was classified by ANNES, qualitative visual reading, main basic rhythm frequency and spectral analysis. The classifications were assessed on the basis of: (i) match with liver function, (ii) prognostic value and (iii) repeatability. RESULTS: All classifications were found to be related to the severity of liver failure, with cognitive findings and a history of previous bouts of HE. All of them had prognostic value on the occurrence of overt HE and on survival. The ANNES based classification was more repeatable than the qualitative visual one, and had the advantage of detecting low power EEG, but its efficiency in analyzing low-grade alterations was questionable. CONCLUSIONS: An entirely automatic - ANNES based - EEG classification of HE can improve the repeatability of EEG assessment, but further improvement of the device is required to classify mild alterations. SIGNIFICANCE: The ANNES based EEG grading of HE needs further improvements to be recommended in clinical practice, but it is already sufficient for detecting normal and clearly altered EEG tracings.

Electroencephalography↗
PubMed2006

Analysis of EEG tracings in frequency and time domain in hepatic encephalopathy.

Spectral EEG analysis in hepatic encephalopathy (HE) is usually performed disregarding the effect of epoch length, statistical errors and equipment noise. A study on these items was carried out. In addition, spectral analysis and a new analysis, performed in time domain, were compared in the assessment of HE. The EEG tracings of 73 cirrhotic patients with HE were analyzed. Artifact-free periods of about 1 min were selected. Equipment noise was measured by short-circuiting all the electrodes. The equipment noise was notable below 1.5 Hz; the best epoch length was 4s and the statistical errors were minimal for the band with the highest relative power. Nineteen per cent of the tracings were unstable. The spectral values were found to be related to liver function and to the degree of HE, whereas the relationship with psychometric variables was poor. The indexes computed by time-domain analysis were found to be better related to psychometric findings. We have provided information on the optimisation of spectral EEG analysis and presented a time-domain analysis giving results related to psychometric tests and liver function.

Aged↗
PubMed2006

Electroencephalographic staging of hepatic encephalopathy by an artificial neural network and an expert system.

AIM OF THE STUDY: To provide an objective EEG assessment of hepatic encephalopathy (HE), we set up and tested an entirely automatic procedure based on an artificial neural network-expert system software (ANNESS). PATIENTS AND METHODS: A training set sample of 50 EEG (group A) and a test sample of 50 EEG (group B) of 100 cirrhotic patients were considered. The EEGs had been visually classified by an expert electroencephalographer, using a modified five-degree Parsons-Simith classification of HE. The efficiency of the ANNESS, trained in group A, was tested in group B. RESULTS: Both the ANNESS and the visually-based classifications were found to be correlated to liver insufficiency, as assessed by the Child-Pugh score (Spearman's coefficient rho=0.485, P<0.0001; rho=0.489, P<0.0001, respectively) and by the biochemical indexes of hepatic function (bilirubin: rho=0.31 vs. 0.27; albumin: rho=-0.13 vs. -0.18; prothrombin time rho=-0.35 vs. -0.52). The classifications were found to be correlated to each other (rho=0.84 P<0.0001, Cohen's kappa=0.55). However, the ANNESS overestimated grade 2 EEG alterations. CONCLUSION: An ANNESS-based classification of EEG in HE provided data comparable with a visually-based classification, except for mild alterations (class 2) that tended to be overestimated. Further optimization of automatic EEG staging of HE is desirable, as well as a prospective clinical evaluation.

Aged↗
PubMed2006

Switch therapy with ciprofloxacin vs. intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in patients with cirrhosis: similar efficacy at lower cost.

BACKGROUND: Intravenous administration of a third-generation cephalosporin is optimal antibiotic treatment for spontaneous bacterial peritonitis. AIMS: To compare an intravenous-oral step-down schedule with ciprofloxacin (switch therapy) to intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis, and to evaluate the impact of terlipressin and albumin in the treatment of type 1 hepatorenal syndrome on mortality. METHODS: A total of 116 cirrhotic patients with spontaneous bacterial peritonitis, were randomly given switch therapy with ciprofloxacin (61 patients) or intravenous ceftazidime (55 patients). All patients who developed type 1 hepatorenal syndrome were treated with terlipressin (2-12 mg/day) and albumin (20-40 g/day). RESULTS: Resolution of infection was achieved in 46/55 patients treated with ceftazidime (84%) and in 49/61 patients treated with ciprofloxacin (80%, P = N.S.). An intravenous-oral step-down schedule was possible in 50/61 patients (82%) who received ciprofloxacin; 45/61 patients (74%) were discharged before the end of antibiotic treatment and completed it at home. The mean saving per patient due to the reduction of hospital stay in the ciprofloxacin group was 1150 . Type 1 hepatorenal syndrome was treated successfully in 12/19 patients (63%). As a consequence, the in-hospital mortality rate due to infection was 10%. CONCLUSIONS: Switch therapy with cephalosporin is more cost-effective than intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in cirrhotic patients who are not on prophylaxis with quinolones.

Administration, Oral↗
PubMed2006

The use of prostaglandins in the immediate postsurgical liver transplant period.

INTRODUCTION: Experimental evidence has suggested that prostaglandins have positive effects on hepatic perfusion after transplantation. However, randomized clinical trials have failed to show their usefulness to decrease the incidence of primary nonfunction. In order to demonstrate its therapeutic role, we performed a clinical study in which PGE1 was administered only after the appearance of posttransplant liver dysfunction. MATERIALS AND METHODS: Forty patients with macroscopic signs of hypoperfusion or lacking bile production at the end of the operation (n = 24) or with an increase in transaminases and fall in biliary production in the first 24 hours postsurgery (n = 16) were administered alprostadil (PGE1; 0.01 mug/kg/min to the maximum plateau of 0.06 mug/kg/min). We measured the mean values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), activated thromboplastin time-ratio (aPTT-r), international normalized ratio (INR), bilirubin, creatinine and plasma nitrogen, PaO(2)/FiO(2) at the start of the treatment and every 6 hours for 48 hours, and daily diuresis. RESULTS: There appeared to be a significant decrease in AST, INR, aPTT-r, and creatinine clearance (P < .05), while there was a significant rise in the blood urea nitrogen (P < .001). ALT and bilirubin did not show significant variations. The PaO(2)/FiO(2) ratio showed a significant decrease (P < .001) in pulmonary vasodilatation. CONCLUSIONS: Prostaglandins used in the manner in our study showed a significant efficiency to improve liver dysfunction after transplantation.

Alprostadil↗
PubMed2005

Spontaneous regression of hepatitis B virus-associated cirrhosis developed in childhood.

We reported two cases of hepatitis B virus infection-related cirrhosis developed during childhood and followed up for more than 20 years. Both the subjects remained untreated, and ultimately regression of cirrhosis was documented by clinical (including ultrasound) and histological examination. Recent studies have already suggested that hepatitis B virus-related cirrhosis may regress after treatment, but this is the first demonstration that hepatitis B virus-associated cirrhosis developed in childhood may be a spontaneously reversible process. Subsidence of virus replication and of necro-inflammatory process and the efficiency of liver regeneration and repair might contribute to this favourable outcome.

Age Factors↗
PubMed2005

P300 latency for the diagnosis of minimal hepatic encephalopathy: evidence that spectral EEG analysis and psychometric tests are enough.

BACKGROUND: No gold standard exists to detect minimal hepatic encephalopathy. Event-related evoked potentials (P300 latency) were proposed as the best tool to assess this condition. EEG spectral analysis and psychometric evaluation are also used to assess minimal hepatic encephalopathy. AIMS: The present study aims at comparing these three techniques. PATIENTS: Eighty-six cirrhotic patients without overt hepatic encephalopathy were studied. METHODS: Patients underwent EEG spectral analysis, psychometric evaluation and P300. P300 latency was age-adjusted; psychometric tests were age- and education-adjusted. Values >2Z were considered to be altered. The alteration of at least two psychometric tests was considered for cognitive impairment. RESULTS: At least one of the three indexes was altered in 61% (CI95% = 49-71) patients; EEG spectral analysis was altered in 41% (CI95% = 30-52%) patients, psychometric performance in 34% (CI95% = 24-45%) and P300 latency in 13% (CI95% = 7-22%). P300 latency was altered only in the patients having EEG spectral analysis or psychometric alterations, but for two cases. Psychometric performance and EEG spectral analysis, but not P300 latency, were correlated with indexes of liver function. CONCLUSIONS: P300 latency provided little additional information and was less related to liver function than EEG spectral analysis and psychometrical investigation.

Aged↗
PubMed2005

Disagreement between acute and chronic haemodynamic effects of nadolol in cirrhosis: a pathophysiological interpretation.

BACKGROUND: The acute effects of beta-blockers may be different from chronic; mechanisms underlying this difference are poorly elucidated. AIM: To assess portal pressure and its pathophysiological determinants after acute and chronic administration of nadolol. METHODS: In 24 patients with cirrhosis and portal hypertension hepatic venous pressure gradient, portal blood flow and resistance to portal blood flow were measured before, 60-90 min after acute administration of nadolol, and after 1 month. Patients were good-responders if hepatic venous pressure gradient was < or =12 mmHg, or decreased by at least 20%. RESULTS: Eleven and 13 patients were good- and poor-responders to acute administration, respectively. Acute poor-responders showed a lower decrease in portal blood flow (P = 0.04) and a less evident decrease in mean arterial pressure (P < 0.001). Eleven and 13 patients were good- and poor-responders to chronic administration, respectively. Chronic poor-responders showed a larger increase in resistance to portal blood flow compared with good-responders (P = 0.01). Disagreement between acute and chronic effects was seen in 12 patients: six were acute good-responders chronic poor-responders and six were acute poor-responders chronic good-responders. Acute good-responders chronic poor-responders patients had the smallest decreases in portal blood flow and in mean arterial pressure after acute administration, while acute poor-responders chronic good-responders showed the largest (P = 0.05 and 0.01). CONCLUSIONS: Disagreement between acute and chronic effects of nadolol on hepatic venous pressure gradient is common. The mechanism responsible is complex, the acute effect being mainly modulated by arterial hypotension and the chronic effect by changes in portal resistance.

Acute Disease↗
PubMed2005

Haeme oxygenase mediates hyporeactivity to phenylephrine in the mesenteric vessels of cirrhotic rats with ascites.

BACKGROUND AND AIMS: Haeme oxygenase could play a role in the pathogenesis of arterial vasodilation in cirrhosis. The aim of this study was to verify the role of haeme oxygenase in the hyporesponsiveness to phenylephrine of small mesenteric arteries in rats with CCl(4) induced cirrhosis, with and without ascites. METHODS: Pressurised small resistance mesenteric arteries were challenged with increasing doses of phenylephrine. Dose-response curves were evaluated under basal conditions, after inhibition of haeme oxygenase with chromium-mesoporphyrin, after inhibition of nitric oxide synthase (NOS) with N(G)-nitro-L-arginine-methyl-ester (L-NAME), and then after inhibition of both NOS and haeme oxygenase. Haeme oxygenase protein expression was also analysed. RESULTS: Twenty six control rats and 35 rats with cirrhosis (17 with and 18 without ascites) were studied. Response to phenylephrine was lower in non-ascitic and ascitic cirrhosis than in controls. Chromium-mesoporphyrin increased the response to phenylephrine only in ascitic cirrhosis (p<0.001). L-NAME increased the response to phenylephrine in controls (p<0.001) and in ascitic and non-ascitic cirrhosis (p = 0.002, p<0.001, respectively) but the final response in non-ascitic cirrhosis was similar to that of control rats while it remained impaired in ascitic cirrhosis. Addition of chromium-mesoporphyrin to L-NAME improved the response to phenylephrine in ascitic cirrhosis (p<0.01), with final values not different from those of the other two groups. Protein expression of the inducible isoform of haeme oxygenase was increased in the mesenteric vessels of cirrhotic rats. CONCLUSION: Haeme oxygenase mediates hyporeactivity to phenylephrine in the mesenteric vessels of experimental cirrhosis with ascites. NOS plays a major role only in the first stage of the disease.

Animals↗
PubMed2005

Comparison between nifedipine and carvedilol in the treatment of de novo arterial hypertension after liver transplantation: preliminary results of a controlled clinical trial.

There is no controlled clinical trial on the treatment of de novo arterial hypertension after liver transplantation (LT) a common complication using calcineurin inhibitors (CNI) for immunosuppressive therapy. The aim of this study was to compare the efficacy and safety of nifedipine, a calcium channel blocker, and carvedilol, an alpha1- and beta-blocker. The study included 50 patients who developed arterial hypertension after LT. The data on the first 30 patients who have completed 12-month follow-up are reported herein. Eighteen patients received nifedipine, and 12 patients received carvedilol. Patients were evaluated monthly at the outpatient clinic for 1 year. If patients developed severe adverse effects to nifedipine, they were switched to carvedilol and vice versa (therapy failure). The two groups were similar for clinical features, indications for LT, immunosuppressive therapy, and baseline blood pressures. A failure of treatment was observed in 9 of 18 patients treated with nifedipine (50.0%) and one of 12 patients treated with carvedilol (8%, P < .025). Nifedipine was effective in 4 of 18 patients, carvedilol, in 4 of 12 patients (22.21% vs 33.3%, P = NS). Two of the nine nonresponders to nifedipine responded to carvedilol. The efficacy of monotherapy was observed in 11 of 40 randomized patients (27.5%). Carvedilol monotherapy is as effective as nifedipine but far better tolerated.

Blood Pressure↗
PubMed2004

Overexpression of squamous cell carcinoma antigen variants in hepatocellular carcinoma.

Pathogenetic mechanisms of hepatocellular carcinoma (HCC) are still unclear and new tools for diagnostic and therapeutic purposes are ongoing. We have assessed whether squamous cell carcinoma antigen (SCCA), a serpin overexpressed in neoplastic cells of epithelial origin, is also expressed in liver cancer. Squamous cell carcinoma antigen was evaluated by immunohistochemistry in 65 HCCs of different aetiology and in 20 normal livers. Proliferative activity was assessed using MIB-1 antibody. In 18 surgical samples, tumour and nontumour liver tissue was available for SCCA cDNA amplification and sequencing. Squamous cell carcinoma antigen was detected in 55 out of 65 (85%) tumour specimens, but in none of the 20 controls. In the majority of the cases, the positive signal was found in the cytoplasm of more than 50% of the hepatocytes. Low or undetectable SCCA (score or=2 (mean+/-s.d.: 2%+/-2.4 vs 7.5%+/-10.3, P<0.05). Squamous cell carcinoma antigen mRNA could be directly sequenced in 14 out of 18 liver tumours but in none of the corresponding nontumour samples. From sequence alignment, a novel SCCA1 variant (G(351) to A) was identified in five cases, while SCCA1 was revealed in six cases and SCCA2 in three cases. In conclusion, SCCA variants are overexpressed in HCC, independently of tumour aetiology. A novel SCCA1 variant has been identified in one third of liver tumours.

Adult↗
PubMed2004

Surface expression of squamous cell carcinoma antigen (SCCA) can be increased by the preS1(21-47) sequence of hepatitis B virus.

A variant of the serpin squamous cell carcinoma antigen (SCCA) has been identified as a hepatitis B virus binding protein and high expression of SCCA has recently been found in hepatocarcinoma. Since HBV is involved in liver carcinogenesis, experiments were carried out to examine the effect of HBV preS1 envelope protein on SCCA expression. Surface and intracellular staining for SCCA was assessed by FACS analysis. Preincubation of HepG2 cells and primary human hepatocytes with preS1 protein or with preS1(21-47) tetrameric peptide significantly increased the surface expression of SCCA, without modification of its overall cellular burden, suggesting a surface redistribution of the serpin. An increase in HBV binding and internalization was observed after pre-incubation of the cells with preS1 preparations, compared to cells preincubated with medium alone. Pretreatment of cells with DMSO, while not influencing SCCA basal expression, was responsible for an increase in the efficiency of HBV internalization and this effect was additive to that obtained after incubation with preS1 preparations. In conclusion, the HBV preS1(21-47) sequence is able to induce overexpression of SCCA at the cell surface facilitating virus internalization, while the increased efficiency of HBV entry following DMSO addition is not mediated by SCCA.

Antigens, Neoplasm↗
PubMed2003

Portal hypertension and portal hypertensive gastropathy in patients with liver cirrhosis: a haemodynamic study.

BACKGROUND/AIM: The relationships between the levels of portal hypertension and the morphologic alterations of gastric mucosa in patients with liver cirrhosis--generally described as portal hypertensive gastropathy--are poorly defined. PATIENTS: In total, 62 patients with cirrhosis of different aetiologies, were examined by endoscopy and measurement of portal hypertension by hepatic venous pressure gradient. RESULTS: Portal hypertensive gastropathy was observed in 49 cases; six patients showed gastric antral vascular ectasia always associated with gastric lesions described as severe portal hypertensive gastropathy with different localizations. Hepatic venous pressure gradient showed severe portal hypertension in 37 cases, and averaged 17.7 +/- 4.3 mmHg. It was much higher in patients with severe lesions (p=0.0004). Hepatic venous pressure gradient in patients with endoscopic signs of isolated antral gastropathy was lower (p=0.04) than in those with isolated lesions in body-fundus. No relationship was found between hepatic function, as assessed by the Child-Pugh score, and portal hypertensive gastropathy. CONCLUSIONS: The present data suggest that the severity of portal hypertensive gastropathy is related to portal hypertension, but portal hypertension is not the sole determinant of the occurrence of endoscopic abnormalities of gastric mucosa. The derangement of liver function does not appear to play any role in the occurrence of portal hypertensive gastropathy.

Endoscopy, Digestive System↗
PubMed2003

Neuropsychological-neurophysiological alterations and brain atrophy in cirrhotic patients.

Psychometric performance has been reported to be related to brain atrophy in cirrhotics, but the relationship between brain atrophy and EEG findings is still unknown. The aim of this study was to ascertain the relationship among brain atrophy, EEG, and cognitive performance in cirrhotics. Sixty-eight cirrhotics (age = 55 +/- 10 years; males-66%) underwent psychometric evaluation (Symbol Digit Test, Trail Making Test-Part A, Scan test), EEG recording and spectral analysis (S-EEG), and brain CT scan. Central brain atrophy was ascertained by the following indexes of brain atrophy: the Evans' index, the bicaudate index, the cella media index, the bifrontal index, and the ventricular index; cortical brain atrophy by the sulci index. The severity of liver failure was assessed by the Child-Pugh score: 18% of patients were Child-Pugh Class A, 50% Class B, and 32% Class C. Central and cortical atrophies were found to be correlated with age, but not with the Child-Pugh score. Psychometric performance and the EEG mean dominant frequency (MDF) were found to be correlated with brain atrophy. Multivariate analysis showed that a poor psychometric performance was independently predicted by EEG slowing (MDF: p < 0.01) and by central brain atrophy (cella media index: p < 0.01). In conclusion, brain atrophy was associated with a poor psychometric performance and EEG alterations in cirrhosis. Both brain atrophy and EEG alterations independently predicted cognitive dysfunction in cirrhotic patients.

Adult↗
PubMed2002

Role of spleen enlargement in cirrhosis with portal hypertension.

The possible relationships between splenomegaly and portal hypertension have been analysed in patients with cirrhosis. In this condition, splenomegaly is not only caused by portal congestion, but it is mainly due to tissue hyperplasia and fibrosis. The increase in spleen size is followed by an increase in splenic blood flow, which participates in portal hypertension actively congesting the portal system.

Endothelins↗
PubMed2001

High levels of soluble tumor necrosis factor superfamily receptors in patients with hepatitis C virus infection and lymphoproliferative disorders.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is associated with a variety of extrahepatic disorders that may relate to direct or indirect effects of virus infection. Increased levels of soluble forms of tumor necrosis factor (TNF) receptors I and II, found in lymphoproliferative and infectious diseases, can interfere with TNF induced apoptotic cell death. The aim of the present study was to evaluate soluble TNF family receptors levels in lymphoproliferative disorders associated with HCV infection. METHODS: One hundred and forty-nine subjects were studied, including 120 anti-HCV positive patients (60 without lymphoproliferative manifestations, 47 with type II cryoglobulinemia and 13 with low-grade B-cell non-Hodgkin's lymphoma (B-NHL)) and 29 anti-HCV negative subjects (19 with low-grade B-NHLs and ten normal controls). RESULTS: Soluble forms of TNF receptor I, TNF receptor II and Fas were significantly higher in HCV positive patients compared with normal controls. The highest levels were found in patients affected by type II cryoglobulinemia or HCV positive lymphoplasmacytoid lymphomas (LP-NHLs), while HCV positive patients without type II cryoglobulinemia or with other B-NHLs had lower values (P < 0.01). CONCLUSIONS: Among HCV infected individuals, very high levels of soluble TNF receptors are significantly associated with type II cryoglobulinemia and LP-NHLs, suggesting that they may be involved in these proliferative disorders.

Adult↗