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L Pagliaro

Publications and source records attributed to L Pagliaro.

At least 19 recordsLinked to original sources
PubMed1997

A randomized controlled trial of high-dose maintenance interferon therapy in chronic hepatitis C.

In chronic hepatitis C virus (HCV) infection, the rate of sustained response to interferon is low. We evaluated, in patients responding to a 26-week course of interferon, the effect of high-dose maintenance therapy in preventing relapse. Three hundred and ten patients with chronic HCV infection (38.3% with cirrhosis, 80.6% with HCV type 1) received interferon alfa-2b for 26 weeks (10 MU tiw for 8 weeks, then 5 MU tiw for 18 weeks). One hundred and twenty-four subjects (40%) normalized aminotransferases, and were allocated randomly either to continue on 5 MU tiw for a further 26 weeks (prolonged therapy group: 60 patients) or to stop interferon (brief therapy group: 64 patients). Fifty-two weeks after stopping interferon the overall sustained biochemical response rate was 13.2% (41/310). The number of patients with normal aminotransferases was comparable between the prolonged and brief therapy groups (30% vs. 35.9%, P = n.s.), and the rate of HCV-RNA clearance was similar (48.8% vs. 42.4%, P = n.s.). The timing of posttreatment relapse was not influenced by the duration of therapy. Fifty-nine patients (19%) did not complete therapy due to adverse effects. Multivariate analysis identified four features predicting sustained biochemical response in subjects normalizing aminotransferases under therapy: negative HCV-RNA at end of therapy, normal aminotransferases at 4 weeks of therapy, high baseline aminotransferases, and high baseline platelets. Infection with HCV type 1 was not a significant predictor of response, due to its high prevalence in our population (80.6%). It is concluded that in patients with chronic hepatitis C mostly infected by HCV type 1, a prolonged high-dose interferon course (900 MU over 52 weeks) did not increase the rate of sustained biochemical response and of HCV-RNA clearance in comparison to a brief course (510 MU over 26 weeks).

Adolescent↗
PubMed1997

The effect of interferon on the liver in chronic hepatitis C: a quantitative evaluation of histology by meta-analysis.

BACKGROUND/AIMS: Several randomized clinical trials of interferon in chronic hepatitis C have examined the histological changes in paired biopsy specimens. We have attempted a quantitative evaluation by meta-analysis. METHODS: Randomized Clinical Trials found by MEDLINE search were included if: a) they compared different IFN regimens with non-active treatment or with each other, b) they obtained biopsies before starting and at the time of stopping IFN in a sizable proportion of the treated and control patients, and c) they assessed the biopsy-specimens semi-quantitatively according to Scheuer's numerical scoring system or Knodell's Histological Activity Index, with quantitation of fibrosis and of lobular, portal and periportal necroinflammation. RESULTS: Seventeen trials were identified, in which 1223 adult patients had been studied. All trials homogeneously pointed towards a favorable interferon effect. The pooled data show a statistically significant histological improvement in treated patients as compared with controls for each of the four Histological Activity Index components and for the total Histological Activity Index score (overall improvement was -0.82 in favor of interferon, p<0.0001, 95% Confidence Interval -1.25 to -0.40). In the ten trials reporting histological changes separately in biochemical responders (primary and sustained responders) and non-responders, histological improvement was confined to the subset of biochemical responders. No change or very little change occurred in non-responders. CONCLUSIONS: Interferon treatment in chronic hepatitis C significantly improves liver histology. The effect of interferon is closely related to biochemical response. Studies assessing histological outcome 1 year or more after interferon treatment in long-term responders and comparatively in non-responders or relapsers would be important to confirm the regression of the necroinflammatory process in the former, as suggested by the normal serum alanine aminotransferase levels.

Adult↗
PubMed1997

Treatment of hepatocellular carcinoma: a systematic review of randomized controlled trials.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. Many treatments have been proposed but considerable uncertainty still remains about their effectiveness. In this review we evaluated the quality, clinical coherence, consistency and results of Randomized Controlled Trials (RCT) of non-surgical treatments for HCC. METHODS: Thirty-seven RCTs examining the effect of different treatments were retrieved using MEDLINE (November 1978 to December 1995) and a review of reference lists. Selected aspects of the quality of design, conduct and reporting were examined. The odds ratio for the probability of surviving up to one year was calculated according to the Mantel Haenszel Peto method and displayed using l'Abbe plots. RESULTS: The 37 RCTs overall included 2803 patients (median 56, range 20-289). Patients prognosis varied widely across studies which also failed to report on important information about their characteristics. Only 10 RCTs had an untreated control group; the remaining 27 compared different regimens of intravenous or intraarterial chemotherapy with or without embolization of hepatic artery, hormono- and immunotherapy regimens. Some evidence of a moderate benefit emerged only from RCTs using tamoxifen and transcatheter arterial embolization vs. no treatment in unresectable patients: pooled odds ratio for 1-year survival were, respectively, 2.0 (95% confidence intervals (CI) 1.1-3.6) and 2.0 (95% CI 1.1-3.6). At 2 years, however, pooled odds ratio were no longer statistically significant for tamoxifen 1.2 (95% CI 0.6-2.6) but was significant for embolization 2.3 (95% CI 1.2-4.6). No evidence of efficacy was detected for embolization as adjuvant therapy in resected or transplanted patients nor for chemotherapy added to intraarterial embolization. CONCLUSIONS: This systematic review of RCTs on HCC, mostly in non resectable patients, indicate that the non-surgical current treatments are ineffective or minimally and uncertainly effective. The three treatment modalities minimally and uncertainly effective (i.e., embolization, tamoxifen and IFN) can deserve further assessment by larger and methodologically more sound randomized trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Does regulatory protein play a role in glucokinase localization?

The enzyme glucokinase has recently been found to be largely responsible for glucose homeostatic responses of both the liver and pancreas. The mechanism(s) of these responses remains unknown but recent studies suggest that the intracellular localization of glucokinase, controlled by glucokinase regulatory protein, may be important. This protein is known to bind to and inhibit glucokinase in a phosphofructose-sensitive manner, and we present evidence for the interaction of these proteins with F-actin. Glucokinase regulatory protein gelled F-actin, and gelation was specifically inhibited by glucokinase and the regulatory protein effectors fructose-1-phosphate (F1P) and fructose-6-phosphate (F6P). These results suggest that glucokinase regulatory protein may play a role in metabolism-sensitive glucokinase localization in vivo.

Actins↗
PubMed1997

Treatment of small hepatocellular carcinoma associated with cirrhosis by percutaneous ethanol injection. A trial with a comparison group.

BACKGROUND: Ethanol injection has been reported to be effective in the treatment of hepatocellular carcinoma, but no controlled randomized trials have been performed. We therefore performed a trial comparing ethanol injection with an untreated, matched historical comparison group in the treatment of hepatocellular carcinoma. METHODS: From 1992 to 1993, 35 patients (14 Child's A and 21 Child's B cirrhosis) with small (< 4 cm) hepatocellular carcinoma associated with cirrhosis were treated by ethanol injection. Each patient was matched with an untreated case (followed up during the period 1984-89) for variables known to have independent prognostic value (age, Child's classification, number of lesions, alpha-fetoprotein, and modality of diagnosis). RESULTS: The 1-, 2-, and 3-year survival rates of ethanol-treated patients were 86% (95% confidence interval (CI), 69-94), 53% (95% CI, 34-68), and 33% (95% CI, 15-52), whereas the survival rates of the comparison group were 75% (95% CI, 56-85), 26% (95% CI, 13-41), and 14% (95% CI, 5-27) (P = 0.01). The 1-, 2-, and 3-year survival rates of Child's A were 100%. 87% (95% CI, 30-97), 71% (95 CI, 33-90), 71% (95% CI, 33-90) in the ethanol-treated patients and 92 (95% CI, 59-99), 43% (95% CI, 23-73), and 21% (95% CI, 23-72) in untreated patients. The 1-, 2-, and 3-year survival of Child's B patients were 76% (95% CI, 59-97), 32% (95% CI, 13-53), and 9% (95% CI, 0.8-33) in the treated group and 61% (95% CI, 40-83), 14% (95% CI, 3-32), and 9% (95% CI, 1-26) in the treated group. CONCLUSIONS: These data suggest that ethanol injection prolongs the life of patients with hepatocellular carcinoma associated with Child's A cirrhosis but seems not to influence the survival of Child's B patients.

Carcinoma, Hepatocellular↗
PubMed1997

Enalapril-associated acute pancreatitis: recurrence after rechallenge.

Three patients with acute pancreatitis diagnosed while they were taking enalapril are described. In two of these patients, enalapril was the only drug taken immediately before the symptoms began, and other etiologies were accurately excluded. In the third patient, the relationship between enalapril and acute pancreatitis was shown by a rechallenge with the drug that resulted in severe acute pancreatitis. This report is a definite demonstration of the relationship between enalapril and acute pancreatitis. We suggest stopping treatment with enalapril in patients suspected of having acute pancreatitis. We also recommend not rechallenging patients with the drug because of the risk of inducing severe acute pancreatitis.

Acute Disease↗
PubMed1996

Health services: an Italian market.

One of the glories of Italy is its capacity to surprise. In out-of-the-way places extraordinary things are suddenly encountered; and this is hardly less true of science than of architecture or music or painting. Italian medicine can boast excellence in many quiet spots. Yet Italy's record in medical science and practice is perceived to be below par, and one reason may be a lack of central coordination--forgivable in a country that had fifty governments in half a century. The latest administration offers a rare chance of political stability and the prospect of reforms. In this profile of Italian medicine The Lancet's guide was Dr Giuseppe Remuzzi, whose central coordination was exemplary.

Acquired Immunodeficiency Syndrome↗
PubMed1996

The molecular nature of the F-actin binding activity of aldolase revealed with site-directed mutants.

We used site-directed mutagenesis of rabbit muscle aldolase, falling ball viscometry, co-sedimentation binding assays, and negative stain electron microscopy, to identify specific residues involved in the aldolase-actin interaction. Three mutants, R42A (Arg --> Ala), K107A (Lys --> Ala), and R148A (Arg --> Ala), had minimal actin binding activity relative to wild type (wt) aldolase, and one mutant, K229A (Lys --> Ala), had intermediate actin binding activity. A mutant with approximately 4,000-fold reduced catalytic activity, D33S (Asp --> Ser), had normal actin binding activity. The aldolase substrates and product, fructose 1,6-bisphosphate, fructose 1-phosphate, and dihydroxyacetone phosphate, reversed the gelling of wt aldolase and F-actin, consistent with at least partial overlap of catalytic and actin-binding sites on aldolase. Molecular modeling reveals that the actin-binding residues we have identified are clustered in or around the catalytic pocket of the molecule. These data confirm that the aldolase-actin interaction is due to specific binding, and they suggest that electrostatic interactions between specific residues, rather than net charge, mediate this interaction. Low concentration of wt and D33S aldolase caused formation of high viscosity actin gel networks, while high concentrations of wt and D33S aldolase resulted in solation of the gel by bundling actin filaments, consistent with a potential role for this enzyme in the regulation of cytoplasmic structure.

Actins↗
PubMed1996

Ascites, pleural, and pericardial effusions in acute pancreatitis. A prospective study of incidence, natural history, and prognostic role.

Ascites and pleural and pericardial effusions can be observed during acute pancreatitis. The aims of this study were to evaluate their incidence, natural history, and prognostic role in patients with acute pancreatitis. One hundred patients consecutively admitted with a diagnosis of acute pancreatitis were prospectively submitted to abdominal, pleural, and cardiac ultrasonography at admission and during follow-up. Ascites was found in 18 patients, pleural effusion in 20, and pericardial effusion in 17. Twenty-four patients of this series had severe pancreatitis; three of them died. All effusions disappeared spontaneously in patients who survived pancreatitis up to two months after dismissal. At multivariate analysis ascites and pleural effusion were demonstrated to be accurate independent predictors of severity. The respective odds ratios were 5.9 [95% confidence interval (CI), 1.5-23.0%) and 8.6 (95% CI, 2.3-32.5%). Furthermore the presence of pleural effusion, ascites, and pericardial effusion were associated with an increased incidence of pseudocyst during follow-up. Ascites and pleural and pericardial effusions are frequent during acute pancreatitis. Pleural effusion and ascites are accurate predictors of severity in these patients.

Acute Disease↗
PubMed1996

Transfusion-associated chronic hepatitis C: alpha-n1 interferon for 6 vs. 12 months.

AIMS: To compare the long-term effects of brief and prolonged therapy with alpha-n1 interferon for transfusion-associated chronic hepatitis C. METHODS: One hundred and sixteen subjects (male/female 48/68, mean age 46.9 years) were studied. Sixty patients were randomised to brief treatment (group 1: interferon 5 Mu/msq. t.i.w. for 2 months, then 3 Mu/msq. t.i.w. for 4 months), and 56 to prolonged treatment (group 2: interferon 5 Mu/msq. t.i.w. for 2 months, then 3 Mu/msq. t.i.w. for 10 months). All were followed for 12 months after stopping interferon. RESULTS: The early response rate was 47.4% (Group 1 [45%], Group 2[50%]. No "breakthrough" reactivations were observed. The early response rate was 19% in patients with and 63% in patients without cirrhosis. Twenty-three (19.8%) subjects stopped therapy. Among 54 evaluable early responders, 21 had a sustained response. The rate of sustained response was comparable in group 1 (18.3%) and group 2 (18.2%). All sustained response subjects and some non-responders were HCV-RNA negative at the end of follow-up. Histological improvement was seen only after sustained response. Cirrhosis developed in 20% of non-responders. Overall, interferon induced a long-lasting remission of chronic hepatitis C in about one of every five patients. CONCLUSIONS: In a population predominantly infected by hepatitis C virus type 1, 12 months of therapy with high doses of interferon does not confer any additional benefit on the early response or sustained response rates as compared to a 6-month course.

Adolescent↗
PubMed1996

HCV viraemia is more important than genotype as a predictor of response to interferon in Sicily (southern Italy).

BACKGROUND/AIMS: To investigate host- and virus-related factors predictive of early and sustained alanine aminotransferase normalization after interferon therapy for HCV-related chronic liver disease, in an area where genotype 1 is highly prevalent. METHODS: We studied 100 patients with HCV-RNA positive chronic liver disease (73 chronic hepatitis and 27 cirrhosis) undergoing alpha-interferon treatment. Thirty-four patients had an early response but relapsed, 15 patients remained into sustained response for at least 12 months after therapy, and 51 patients did not respond. Serum HCV-RNA levels were assessed by bDNA (Chiron), and genotype by LiPA (Innogenetics) and by sequencing of the 5' non-coding region. RESULTS: Mean pre-treatment HCV-RNA level (x 10(3) genome equivalents/ml +/- SD) was lower in sustained responders (3854 +/- 7142) than in relapsers (9587 +/- 10163) or in non-responders (5709 +/- 6618). HCV subtype 1b was highly prevalent (82%), while types 1a, 2a, 3 and 4 were rare (about 5% each). However, the prevalence of 1b was much lower (31%) under 40 years of age. The prevalence of subtype 1b among sustained responders (74%) was similar to that observed among relapsers (82%) or non-responders (84%), but some nucleotide substitutions in the putative RNA loop of the 5' non-coding region were seen only among relapsers or non-responders. Multiple logistic regression model showed that early response to interferon was predicted by absence of cirrhosis and a pre-treatment HCV-RNA level below 350. Sustained response to interferon was predicted by pre-treatment HCV-RNA level below 350 and a low fibrosis score. CONCLUSIONS: Among patients with hepatitis C from an area where subtype 1b is highly prevalent, absence of cirrhosis and low pre-treatment serum HCV-RNA level are the most important predictors of response to IFN. Some nucleotide substitutions found in the 5' non-coding region of subtype 1b are associated with non-response or relapse.

Adult↗
PubMed1996

Mortality in patients with Crohn's disease.

BACKGROUND: No data on mortality for Crohn's disease are available from southern Europe. METHODS: Five hundred and thirty-one patients with Crohn's disease were observed in our unit between 1973 and 1993. In 325 patients the first diagnosis was made in our hospital. In this consecutive incidence series, in which the follow-up was 99% complete, the standardized mortality rate (SMR) was calculated. RESULTS: Nine deaths were observed, against 9.25 expected. The SMR was 0.97 (95% confidence interval (CI), 0.4-1.8). The relative risk of dying was significantly higher in the female group in the first 5 years after diagnosis (SMR, 10.3; 95% CI, 2.30-30.2). There was an excess of deaths from tumors of the digestive organs (1 observed, 0.37 expected). CONCLUSIONS: These results show that in our geographic area the mortality from Crohn's disease was not increased as shown in other community studies.

Adolescent↗
PubMed1996

Fulminant hepatic failure in adult onset Still's disease.

Adult onset Still's disease (AOSD) is a well characterized rheumatoid disorder with frequent liver involvement. This is usually asymptomatic but severe hepatic failure has occasionally been reported. We describe a 44-year-old woman who developed acute liver failure 2 months after presenting symptoms of AOSD. Full etiologic evaluation was done and all other causes of liver failure were excluded. She underwent emergency orthotopic liver transplantation but developed disseminated intravascular coagulation with acute renal failure, seizures, and coma, and died after 48 hours.

Acute Kidney Injury↗
PubMed1995

Hepatitis C virus infection as a determinant of behavior in type 1 autoimmune hepatitis.

To determine if hepatitis C virus infection influences the behavior of type 1 autoimmune hepatitis and to assess the performance parameters of third-generation immunoassays for viral infection in this disease, 64 patients with different patterns of disease behavior were assessed retrospectively for antibodies to hepatitis C virus by third-generation enzyme-linked immunosorbent assay and recombinant immunoblot assay and for HCV RNA by polymerase chain reaction. Hepatitis C virus RNA was detected in seven patients (11%) and antibodies to hepatitis C virus were found in five (8%). All patients who had an acute onset of illness or who sustained remission after therapy lacked HCV RNA in serum. In contrast, four of 31 patients who relapsed (13%) and three of 17 patients who failed treatment (18%) had HCV RNA in serum. Patients with HCV RNA were indistinguishable from those without HCV RNA; in three patients, infection was recognized only by testing for HCV RNA. Four of seven patients with HCV RNA responded fully to corticosteroids, although each relapsed after drug withdrawal. Smooth muscle antibodies (43% versus 91%, P = 0.006) and concurrent smooth muscle and antinuclear antibodies (0% versus 60%, P = 0.003) occurred less frequently in patients with HCV RNA than in counterparts without HCV RNA. The specificity of the third-generation enzyme immunoassay was 98% and its overall predictability was 94%. Its sensitivity, however, was 57% and false positive results occurred in 20%. Hepatitis C virus infection is an uncommon determinant of disease behavior in type 1 autoimmune hepatitis, but it may be present in relapse or treatment failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

An optical pressure chamber designed for high numerical aperture studies on adherent living cells.

We have developed an optical pressure chamber designed for use with high numerical aperture oil immersion microscope objectives at working pressures up to 1,000 psi (67 atm abs). The chamber is optimized for studies of living, adherent, cultured mammalian cells using high resolution epifluorescence and phase contrast microscopy, and biophysical techniques such as fluorescence redistribution after photobleaching and optical trapping. The primary optical window assembly of the chamber can be removed and placed into a standard 35-mm tissue culture dish, allowing for culture, microinjection, and micromanipulation of adherent cells before they are loaded into the chamber. The chamber is designed to fit into a commercially available stage heater for temperature control, and we used a computer-controlled high pressure liquid chromatography pump for pressure control. A graphic software interface allows the user to program "dive" profiles and to link temperature and pressure data with digital image files of specimens under study. A minor modification of the present design will allow perfusion at high pressure.

Adhesives↗
PubMed1994

Smoking habits and recurrence in Crohn's disease.

BACKGROUND/AIMS: Smoking may be a risk factor for surgical recurrence of Crohn's disease. However, other variables associated with recurrence could be confounding factors for smoking. The aim of this study was to evaluate the role of smoking as an independent predictor of clinical, surgical, and endoscopic recurrence. METHODS: In a series of 182 patients who underwent surgery for Crohn's disease, a multivariate analysis was performed that included all of the significant variables associated with recurrence: sex, age at diagnosis, time between onset of symptoms and surgery, site of disease, indication for surgery, extent of disease, extraintestinal manifestation, and smoking habit. RESULTS: Independent predictors of clinical recurrence by the Cox proportional hazard model were smoking (hazard ratio, 1.46; 95% confidence interval [CI], 1.1-1.8), extraintestinal manifestations (hazard ratio, 1.61; 95% CI, 1.0-2.5), and extent of disease (hazard ratio, 1.57; 95% CI, 1.0-2.4). Smoking was the only significant predictor of surgical recurrence (hazard ratio, 2.0; 95% CI, 1.2-2.3). For endoscopic recurrence, logistic regression showed that smoking (odds ratio, 2.2; 95% CI, 1.2-3.8) and extent of disease (odds ratio, 2.6; 95% CI, 1.0-6.7) were predictive factors of recurrence. CONCLUSIONS: Smoking is an independent risk factor for clinical, surgical, and endoscopic recurrence in Crohn's disease.

Adult↗