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Biomedical subjects

L Pagliaro

Publications and source records attributed to L Pagliaro.

At least 73 records · Page 4Linked to original sources

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↗

A computer-interfaced falling ball viscometer.

We have developed a system that greatly facilitates viscosity measurement under low-shear conditions, based upon a falling ball viscometer interfaced to a personal computer. Three optical sensors indicate the rate of passage of a steel ball falling through a micro-capillary tube, and a potentiometer detects the angle of the tube. The resulting data are passed from a custom program with a graphical user interface to a spreadsheet. The spreadsheet then calculates and stores a value for the viscosity of the sample, using the data passed to it from the viscometer, and a look-up table of stored slope and intercept values calculated from precision viscosity standards. We used the viscometer to determine the kinetics of actin polymerization, and to measure the viscosity of F-actin-aldolase gels. This system provides significantly greater reproducibility and speed in data acquisition than does the traditional 'eyeball and stopwatch' method, and data reduction is virtually instantaneous.

Actins↗

Terlipressin or vasopressin plus transdermal nitroglycerin in a treatment strategy for digestive bleeding in cirrhosis. A randomized clinical trial. Liver Study Group of V. Cervello Hospital.

Between 1988 and 1990 an unblinded, randomized trial of terlipressin or vasopressin plus transdermal nitroglycerin, as part of a treatment strategy including emergency sclerotherapy for actively bleeding varices, was conducted during 165 admissions in 137 patients with cirrhosis and upper digestive bleeding. Eighty-four patient admissions were assigned to terlipressin (2 mg every 6 h) and 81 to vasopressin (0.4 to 0.8 unit per min) plus transdermal nitroglycerin (20 to 80 mg). The two groups were comparable for relevant clinical data, but there were slightly more patients with hepatocellular carcinoma or terminal conditions in the terlipressin group. After the 24-h study period, failure to control bleeding was 20/84 (25%) in the vasopressin and 14/81 (17%) in the terlipressin group (p = 0.19). Corresponding figures for patients bleeding from varices (emergency sclerotherapy in 43 and 45, respectively) were 13/55 (24%) and 5/56 (9%; p = 0.035), from other sources 5/16 (31%) and 2/15 (13%; p = 0.23), from undefined sources 2/10 (20%) and 7/13 (54%; p = 0.1). In a logistic multivariate regression model the odds ratio for terlipressin adjusted for prognostic factors was 0.45 (p = 0.07). There were seven major side effects requiring treatment discontinuation in the vasopressin and one in the terlipressin group. These results suggest that terlipressin alone is as effective as vasopressin plus transdermal nitroglycerin, with less severe side effects, in 24-h control of upper gastrointestinal bleeding in patients with cirrhosis.

Administration, Cutaneous↗

Third-generation hepatitis C virus tests in asymptomatic anti-HCV-positive blood donors.

This study evaluated the performance of third-generation anti-HCV assays in blood donors who were positive by second-generation anti-HCV, and assessed any possible relationship between antibody patterns, HCV replication and liver damage. Fifty-two second-generation enzyme immunoassay-positive asymptomatic Italian blood donors were retested for anti-HCV by third-generation enzyme immunoassay and recombinant immunoblot assay (Ortho third-generation enzyme immunoassay, third-generation recombinant immunoblot assay), utilising recombinant C33c and NS5 and synthetic peptide C100 and C22 antigens, and for HCV-RNA by "nested" polymerase chain reaction with 5' region primers. Alanine aminotransferases were tested monthly for 6 months. Two out of 52 second-generation enzyme immunoassay-positive donors were third-generation enzyme immunoassay, third-generation recombinant immunoblot assay and HCV-RNA negative. Among 50 third-generation enzyme immunoassay-positive cases, two had a third-generation enzyme immunoassay optical density < or = 1: one was third-generation recombinant immunoblot assay and HCV-RNA negative, and the other was third-generation recombinant immunoblot assay "indeterminate" and HCV-RNA-positive. The remaining 48 cases had third-generation enzyme immunoassay optical density > 1: six were third-generation recombinant immunoblot assay negative (one HCV-RNA+ve), eight "indeterminate" (two HCV-RNA+ve) and 34 positive (22 HCV-RNA+ve). All "indeterminate" subjects reacted only to C22. HCV-RNA was positive in 22/34 cases with positive third-generation recombinant immunoblot assay (two or more Ags), 3/9 "indeterminate" and 1/11 negative. Alanine amino-transferases were abnormal in 13 cases with positive third-generation recombinant immunoblot assay, one was "indeterminate" and three were negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Fibre optic scrambling in light microscopy: a computer simulation and analysis.

Optical fibres bent in two mutually perpendicular planes have proven useful for randomizing illumination in light microscopes. These optical scramblers can increase the resolution and/or contrast obtained with several modes of light microscopy. Here, computer simulations are used to investigate several parameters affecting light randomization in curved optical fibres in order to further the theoretical basis for scrambler design. Light passing through 90 degrees bends of optical fibre of varying radii of curvature was modelled by ray tracing in two dimensions, and scrambling mechanisms were observed. The effects of varying the position and angle of entry of light on the phase and direction of propagation of the emergent light were determined. It was found that (a) thorough scrambling does not necessarily require high numerical aperture (NA) entry of light into the fibre, (b) considerable order persists after a single 90 degrees bend of an idealized fibre and (c) a higher degree of scrambling (at the cost of transmission efficiency) is achieved in more tightly curved fibres. The pathlength variations introduced by scrambling proved smaller than typical laser coherence lengths, requiring temporal scrambling (vibrating the fibre).

Computer Simulation↗

Interferon-alpha for chronic hepatitis C: an analysis of pretreatment clinical predictors of response.

To identify predictors of short-term and sustained ALT normalization after interferon treatment in adult patients with chronic hepatitis C, we performed a meta-analysis of individual patients' data, with construction and cross-validation of a prediction rule, in 361 patients from two randomized trials. In one trial, 116 subjects with transfusion-related chronic hepatitis C were treated with lymphoblastoid interferon (5 MU/m2 three times a week for 2 mo, then 3 MU/m2 three times a week for 4 or 10 mo). In the other study, 245 patients with community-acquired chronic hepatitis C received recombinant interferon-alpha 2b (10 MU three times a week for 2 mo, then 5 MU three times a week for 4 mo; then random allocation of subjects with normal aminotransferase levels to stop or continue interferon for a further 6 mo). Overall, 164 subjects (45%; 95% confidence interval, 40% to 50%) had short-term responses; 61 (18%; 95% confidence interval, 14% to 22%) maintained sustained responses. Sixty patients (17%; 95% confidence interval, 13% to 21%) withdrew from treatment because of side effects or subjective intolerance. Logistic regression analysis showed that short-term and sustained response were independently predicted by lobular structure on pretreatment liver biopsy (p < 0.0001) and by short disease duration, defined as the time elapsed since transfusion in posttransfusion cases or since the first observation of abnormal aminotransferase levels in cryptogenic disease (p < 0.01). Rules to predict short-term and sustained response to interferon were derived from these items, showing a discriminatory ability of 0.73 and 0.70.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Biliary sludge and gallstones in pregnancy: incidence, risk factors, and natural history.

OBJECTIVE: To evaluate the incidence and symptoms of and risk factors for biliary sludge and gallstones during pregnancy and to assess the natural history of these conditions in the first year after delivery. DESIGN: Cohort study. PATIENTS: A total of 272 pregnant women recruited in the first trimester. MEASUREMENTS: Biliary sludge and gallstones were diagnosed using ultrasonography, both during pregnancy and after delivery. Predictors of the presence or disappearance of sludge and stones were examined. MAIN RESULTS: Overall, from the first trimester of pregnancy until the immediate postpartum period, 67 women were newly diagnosed with biliary sludge, and 6 women were newly diagnosed with gallstones. The respective incidence rates were 31% (95% Cl, 25% to 37%) and 2% (95% Cl, 0.2% to 4%). During pregnancy, 28% of women experienced biliary pain, which was associated only with presence of stones. After delivery, 92 women had sludge and 23 had stones. Sludge disappeared in 61% of these women (Cl, 50% to 73%) after a mean follow-up of 5 months, and stones disappeared in 28% of women (Cl, 10% to 46%) after 9.7 months of follow-up. CONCLUSIONS: Biliary sludge occurred frequently during pregnancy but was generally asymptomatic and often disappeared spontaneously after delivery. Gallstones were much less frequent and were more likely to be associated with biliary pain.

Adult↗

Lactitol in treatment of chronic hepatic encephalopathy. A meta-analysis.

The efficacy and side effects of lactitol in the treatment of chronic hepatic encephalopathy was compared to that of other disaccharides in a meta-analysis of published randomized clinical trials (RCTs). The outcomes assessed were: (1) the rate of patients free from episodes of clinically detectable encephalopathy, and (2) the rate of patients free from one or more side effects in the different treatment groups. Four RCTs were eligible for analysis; in three lactitol was compared to lactulose, in one the alternative treatment was lactose in lactase-deficient patients. The methodological quality of these studies was high. Meta-analysis showed that lactitol was as effective as other disaccharides in the treatment of encephalopathy: pooled odds ratio was 0.83, 95% confidence interval was 0.38-1.82. Results were not sensitive to the use of alternative methods of counting and attributing events in these trials. Patients experienced fewer side effects during treatment with lactitol, but the pooled odds ratio was not statistically significant. In all studies lactitol was considered more palatable. Clinical effectiveness of lactitol, in long-term treatment of chronic encephalopathy, is similar to those of lactulose. It seems that lactitol has lower side effects than lactulose. Future RCTs with a double-blind design could be mainly aimed at evaluating the side-effect profile of the two disaccharides.

Chronic Disease↗

Ursodeoxycholic acid for symptomatic primary biliary cirrhosis. Preliminary analysis of a double-blind multicenter trial. Italian Multicenter Group for the Study of UDCA in PBC.

The administration of ursodeoxycholic acid, a hydrophilic bile acid not hepatotoxic to humans, has been suggested for treatment of primary biliary cirrhosis to improve cholestasis and reduce hepatocellular damage. Efficacy of treatment has been studied mainly in patients with asymptomatic or early-stage disease. In January 1988, to establish the efficacy and safety of ursodeoxycholic acid in a population with more severe disease, we started a multicenter, double-blind, placebo-controlled trial in patients with symptomatic disease, that is, with pruritus or serum bilirubin exceeding 2 mg/dl. Forty-four patients were assigned to ursodeoxycholic acid, 500 mg daily (corresponding to about 8.7 mg/kg body weight in these patients), and 44 to a placebo. As planned at the beginning of the study, a preliminary analysis was performed when all patients had been followed for at least 6 months (33 patients up to 12 months). Pruritus, self-evaluated by the patients, and cholestyramine consumption, as recorded in a diary, decreased significantly (p < 0.01) in both groups. In patients who initially had abnormal levels, serum bilirubin decreased significantly (p < 0.05) in the ursodeoxycholic acid group compared to placebo. After 6 months the following were also significantly better in the ursodeoxycholic acid than in the placebo group: a composite weighted biochemical index taking into account the changes in serum bilirubin, alkaline phosphatase, gamma-GT and AST (p < 0.001); serum prealbumin (p < 0.05); IgG (p < 0.01) and IgM (p < 0.01) levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Bilirubin↗

Interferon treatment in patients with chronic hepatitis B: a meta-analysis of the published literature.

The randomised clinical trials testing the effectiveness of interferon treatment on Chronic Hepatitis B patients were reviewed by means of meta-analysis. Twenty-two trials, published between 1987 and 1990, have identified where 1290 adult patients had been studied. Overall, interferon increased the rates of serum HBV-DNA clearance and amino-transferases normalization about 3 times at one year. However, when an analysis of internal consistency, clinical relevance and methodology of these studies was made, the trials were not sufficient to confirm the clinical effectiveness of the treatment since they had been planned for short-term assessment based on biochemical and viral end points alone. The link of these end points to other outcomes of more obvious clinical relevance (i.e. evolution to cirrhosis or deterioration of cirrhosis, death) is, in fact, questionable and thus the value of a meta-analysis based on currently available trials is uncertain as a source for practical guidelines. We conclude that the effectiveness of interferon in patients with chronic hepatitis B has yet to be confirmed by long-term prospective studies which assess the outcome by clinically meaningful end points such as cirrhosis, liver failure, or death.

Adolescent↗

Clinical presentation and ultrasonography in the diagnosis of pancreatic cancer.

One thousand twenty patients consecutively admitted because of a clinical suspicion of pancreatic cancer were investigated to evaluate the accuracy of simple clinical, laboratory, and ultrasonographic data in the diagnosis of pancreatic cancer. Age, weight loss, recent-onset diabetes mellitus, palpable abdominal mass or gallbladder, elevated serum bilirubin or alkaline phosphatase levels, and ultrasonography were significant criteria in discriminating 80 pancreatic cancers from 940 controls. The most sensitive criteria were ultrasonography (83%), weight loss (66%), and bilirubin level of > 3 mg/dl (61%); the most specific were ultrasonography (99%), recent-onset diabetes (97%), and a distended palpable gallbladder (94%). Only ultrasonography demonstrated an elevated positive predictive value (86%), while weight loss, elevated bilirubin and alkaline phosphatase, besides ultrasonography had an elevated negative predictive value (95%). These results show that advanced pancreatic cancer may be excluded with simple clinical and laboratory data; ultrasonography can confirm the diagnosis with a high degree of accuracy. We suggest that the results of any new diagnostic tests for pancreatic cancer be compared with these clinical findings.

Adult↗

Immunoblotting as a confirmatory test for antimitochondrial antibodies in primary biliary cirrhosis.

Primary biliary cirrhosis is characterised by the presence of antimitochondrial antibodies which are directed against components of mitochondrial dehydrogenase complexes. The specificity of antimitochondrial antibodies for primary biliary cirrhosis as detected by immunoblotting was investigated. Commercially available preparations of pyruvate and oxo-glutarate dehydrogenases and beef-heart mitochondria were used as source of antigens. Sera from 47 primary biliary cirrhosis patients (46 of whom were antimitochondrial antibody positive by immunofluorescence), 16 non-primary biliary cirrhosis patients (antimitochondrial antibody positive by immunofluorescence), 23 liver-kidney microsomal antibody positive chronic active hepatitis patients, and 32 patients with connective tissue diseases were examined. Of the 47 subjects with primary biliary cirrhosis, 43 (91%) and 13 (28%) tested positive by immunoblotting for pyruvate and oxo-glutarate dehydrogenase, respectively. Only three primary biliary cirrhosis patients were negative for both antigens, including the only one shown to be antimitochondrial antibody negative by immunofluorescence. The other two patients were positive by immunoblotting with beef-heart mitochondria. In contrast, only three of 16 (19%) non-primary biliary cirrhosis patients who were antimitochondrial antibody positive by immunofluorescence tested positive by immunoblotting (for both pyruvate dehydrogenase and beef-heart mitochondria). None of the 23 liver-kidney microsomal antibody positive and the 32 patients with rheumatic diseases were positive by immunoblotting with any antigen. Our data show that immunoblotting with commercially available oxo-acid dehydrogenases is a reproducible method for the detection of antimitochondrial antibodies highly specific for primary biliary cirrhosis.

Adult↗

[Ademetionine: the state of the art and future prospects].

Ademethionine is a biological molecule mostly produced in the liver and involved in several metabolic pathways. Two of them, the transmethylation and the transulfuration pathways, are particularly important for the physiological activity of the hepatocyte. The first one is responsive for the methylation of membrane phospholipids, a reaction which restores the membrane fluidity and therefore allows a normal and correct role of the hepatocyte. The transulfuration pathway leads to the synthesis of compounds such as glutathione and taurine, which are involved in detoxication processes. Patients with liver diseases of different etiology, and especially patients with chronic diseases, have endogenous ademethionine deficiency. This leads to a malfunctioning of the hepatocyte, which ends up to be damaged in its structure and normal activity. Besides the overplus of methionine, not used for the synthesis of ademethionine, gives rise to high plasma levels of the amino acid. The pharmacological supply of ademethionine enhances the two metabolic pathways and avoids the overplus of methionine. The regeneration of transmethylation and transulfuration restores the normal secretory and excretory activity of the liver cell, and therefore leads to a resolution of cholestasis and removal of toxic compounds from liver parenchyma and plasma. Several experimental and clinical studies have shown the therapeutic efficacy and tolerability of ademethionine in hepatopathic patients with cholestasis. Preliminary experimental data suggest for ademethionine not only an anticholestatic effect, but possibly an anti-fibrotic one.

Chronic Disease↗

Prevention of first bleeding in cirrhosis. A meta-analysis of randomized trials of nonsurgical treatment.

OBJECTIVE: To assess the effectiveness of beta-blockers and endoscopic sclerotherapy in the prevention of first bleeding and reduction of mortality in patients with cirrhosis and esophagogastric varices. DATA SOURCES: Pertinent studies were selected using MEDLINE (1980 to 1990), reference lists from published articles or reviews, and congress abstract lists. STUDY SELECTION: Randomized trials comparing beta-blockers or sclerotherapy with a nonactive treatment. Nine randomized clinical trials of beta-blockers and 19 trials of sclerotherapy were reviewed. Seven trials of beta-blockers and 15 of sclerotherapy were published as full papers. DATA EXTRACTION: Crude rates of bleeding and death in treated and control groups were extracted from each trial by three independent observers according to the intention-to-treat principle. The quality of published papers was systematically assessed and scored. DATA SYNTHESIS: The Mantel-Haenszel-Peto method was used for statistical evaluation of heterogeneity and for pooling of the results. No substantial heterogeneity was found, and the incidence of bleeding in trials of beta-blockers was significantly reduced (pooled odds ratio, 0.54; 95% CI, 0.39 to 0.74), particularly in patients with large or medium-sized varices or in those with varices and a hepatic vein pressure gradient above 12 mm Hg; however, only a trend toward reduced mortality was obtained. Sclerotherapy trials were highly heterogeneous in the direction of the treatment effects on both bleeding (pooled odds ratio, 0.6; CI, 0.49 to 0.74) and mortality (pooled odds ratio, 0.76; CI, 0.61 to 0.94). The quality of the trials and the rate of bleeding in the untreated groups were the major sources of heterogeneity. The favorable results of sclerotherapy were obtained in trials with high bleeding rates among controls; several of these trials had a low quality score. CONCLUSIONS: Beta-blockers may be recommended for prevention of first bleeding in cirrhotic patients with varices who have a high risk for bleeding. The effectiveness of sclerotherapy remains undetermined. Further trials in high-risk patients may prove useful if improved criteria to predict bleeding risk become available.

Adrenergic beta-Antagonists↗