Biomedical subjects

M Torchio

Publications and source records attributed to M Torchio.

At least 19 recordsLinked to original sources

PubMed2001

A modular approach for representing and executing clinical guidelines.

In this paper, we propose an approach for managing clinical guidelines. We outline a modular architecture, allowing us to separate two conceptually distinct aspects: the representation (and acquisition) of clinical guidelines and their execution. We propose an expressive formalism, which allows one to deal with the context-dependent character of clinical guidelines and also takes into account different temporal aspects. We also describe our tool for acquiring clinical guidelines, which provides a user-friendly interface to physicians, and automatically detects many forms of syntactic and semantic inconsistencies in the guidelines being acquired. In the second part of the paper, we describe a flexible engine for executing clinical guidelines (e.g. for clinical decision support applications, for medical education, or for integrating guidelines into the clinical practice), focusing our attention on temporal issues.

Artificial Intelligence↗

PubMed2001

Evidence of an increased nitric oxide production in primary biliary cirrhosis.

OBJECTIVE: Although possible implications of nitric oxide in the pathophysiology of liver cirrhosis have been extensively studied, until now few articles have addressed the assessment of nitric oxide production in primary biliary cirrhosis. This study was directed to evaluate circulating nitrosyl-hemoglobin levels as well as neutrophil elastase and soluble adhesion molecule concentrations in this condition, by assuming these parameters as possible markers of either inflammatory response or neutrophil activation. METHODS: Laboratory investigations were performed in 30 patients with primary biliary cirrhosis, in 13 patients with postviral and/or alcoholic cirrhosis, and in a group of eight subjects with chronic hepatitis. RESULTS: Although no difference was detected with respect to chronic hepatitis subjects, higher levels of nitrosyl-hemoglobin adducts were found in primary biliary cirrhosis patients than in postviral or alcoholic cirrhotics and in normal subjects (3.55+/-1.75 arbitrary units vs 1.95+/-0.57 and 0.84+/-0.34, p = 0.0004 and p < 0.0001, respectively). Similarly, more elevated concentrations of neutrophil elastase (213.7+/-192.0 microg/L vs 51.1+/-34.3 and 38.0+/-11.5, p < 0.0001 and p < 0.0001, respectively) as well as of soluble forms of intercellular adhesion molecule 1 and endothelial-leukocyte adhesion molecule 1 were shown in primary biliary cirrhosis patients than in subjects with cirrhosis of other etiologies and in controls. CONCLUSIONS: Highly enhanced nitric oxide production in primary biliary cirrhosis could be related to the development of strong inflammation and at least partially to neutrophil activation, thus suggesting a putative role of these cellular mediators in the development of liver damage owing to their ability to synthesize and release a wide variety of important factors, including elastase and nitric oxide.

Adult↗

PubMed2000

Executing clinical guidelines: temporal issues.

In our previous work, we proposed a domain-independent language to describe clinical guidelines and a graphical tool to acquire them. In this paper, we describe an approach to execute clinical guidelines. We propose a flexible execution engine that can be used in clinical decision support applications, and also for medical education, or for integrating guidelines into the clinical workflow. We also focus our attention on temporal issues in the execution of guidelines, including the treatment of composite, concurrent and/or cyclic actions.

Databases as Topic↗

PubMed2000

Validation of ICTERUS, a knowledge-based expert system for Jaundice diagnosis.

The study aimed to describe an example of the assessment and validation of knowledge-based clinical expert systems. The paper focuses on ICTERUS, an expert system for jaundice diagnosis. It describes system design, the methodology applied for upgrading and validating the program, and the most important outcomes of the validation procedure. The clinical validation of the system on a very large European database (Euricterus Project) shows that diagnostic conclusions are reliable in about 70% of eligible cases. This figure appears acceptable for a system which provides decision support only on the basis of clinical data, assuming that the final decision is achieved under user responsibility. Expected biases, limitations and inconsistencies in the practical application of the system are discussed.

Analysis of Variance↗

PubMed1998

Prediction by mathematical simulation of different pathophysiological effects on D-sorbitol bioavailability.

In this study a mathematical model was applied to predict how changes in hepatic extraction ratio (E), fractional portal inflow (P) and renal elimination ratio (R) may affect fractional D-sorbitol bioavailability in cirrhotic patients. D-sorbitol bioavailability was computed as the ratio between cumulative urinary outputs measured after infusion into the superior mesenteric (Uma) or the hepatic artery (Uha) and a systemic vein (Usv). The present work was aimed at explaining by mathematical simulation the very large difference observed in the regression lines when plotting Uma or Uha against Usv values. The study was performed by considering a pathophysiological model of the hepatic circulation and simulating independent variations of the above considered parameters or assuming particular pathophysiological conditions like hepatic arterialization and hepatofugal flow. Computational results account for the wide dispersion of experimental data obtained in previous studies and provide reasonable explanations of unexpected findings.

Biological Availability↗

PubMed1998

Arterial-venous shunting in liver cirrhosis.

Controversial data exist in the literature about the presence and clinical relevance of hepatic arterial-venous shunting. An interesting opportunity for reconsidering the problem has been provided by the use, in the study of liver function, of D-sorbitol, a substance whose first-pass hepatic extraction is very high in normal subjects, while being directly related to circulatory alterations in liver cirrhosis. Because of this property, the systemic bioavailability of D-sorbitol during hepatic arterial infusion can be assumed to reflect arterial-venous shunting. Thirteen biopsy-proven cirrhotic patients (ages 35-66 years), who required diagnostic arterial catheterization, entered the study. Patients were studied on two subsequent days, in which a sterile pyrogen-free solution (1.5%) of D-sorbitol was administered by direct low-rate infusion (15 mg/min for 20 min) into the hepatic artery and the systemic circulation, respectively. Urine samples were spontaneously collected for 8-hr periods before and during/after each infusion. The hepatic arterial bioavailability of D-sorbitol was calculated as the ratio between the net cumulative urinary outputs of D-sorbitol after infusions into the hepatic artery and the systemic vein. Observed values confirm the existence and the large variability (0-88.7%) of hepatic arterial-venous shunting in cirrhotic patients.

Adult↗

PubMed1998

Short-term effects of transjugular intrahepatic portosystemic shunt (TIPS) on functional liver plasma flow in patients with advanced cirrhosis.

AIMS/BACKGROUND: TIPS, an effective procedure applied for the treatment of complications of portal hypertension, is potentially followed by worsening of the hyperdynamic circulation of cirrhosis and the impairment of liver function. The aim of the present study was to evaluate short-term changes of functional liver plasma flow after application of TIPS, using the hepatic (extrarenal) clearance of D-sorbitol (S-HCl). METHODS: Twenty-five cirrhotic patients submitted to TIPS for prevention of variceal rebleeding entered the study. At steady-state, during constant infusion of a solution of D-sorbitol (25 mg/min), appropriate blood and urine samples were collected in order to calculate S-HCI before and 120 min after TIPS opening. In addition, the hepatic extraction ratio of D-sorbitol was directly measured at the level of the right (Er), where TIPS was applied, and of the left (El) hepatic veins; meanwhile the portocaval gradient (PCG) was registered, before and after stent dilation. A comparison of values obtained before and after TIPS application was performed by Student's t-test for paired data. RESULTS: After application of TIPS, a substantial reduction was observed in PCG (12.1+/-4.2 vs 24.8+/-4.3 mmHg; p<0.001) and Er values (20.6+/-14.8 vs 57.5+/-22.3 %; p<0.001) but not El values (47.4+/-22.0 vs 53.4+/-21.4 %; p=0.178). S-HCl measured 120 min after TIPS opening was not statistically different from pre-TIPS values (389.2+/-212.1 vs 394.6+/-152.7 ml/min; p=0.892), although S-HCl variations in Child-Pugh class B patients were positively correlated with portal pressure variations (r=0.63, p=0.016). CONCLUSION: Our results demonstrate that in patients with advanced cirrhosis, TIPS procedure, while effective in reducing portal hypertension, does not lead to alterations in the functional liver plasma flow within the first 2 h.

Aged↗

PubMed1998

Contextual and temporal clinical guidelines.

In this paper, we propose an approach for managing clinical guidelines. We sketch a modular architecture, allowing us to separate conceptually distinct aspects in the management and use of clinical guidelines. In particular, we describe the clinical guidelines knowledge representation module and we sketch the acquisition module. The main focus of the paper is the definition of an expressive formalism for representing clinical guidelines, which allows one to deal with the context dependent character of clinical guidelines and takes into account different temporal aspects.

Computer Systems↗

PubMed1993

Removal systems of immunoglobulin A and immunoglobulin A containing complexes in IgA nephropathy and cirrhosis patients. The role of asialoglycoprotein receptors.

BACKGROUND: Whereas the complex removal routes hypothesized for IgA containing immune complexes (IC) and macromolecules can be adequately analyzed by a recently proposed IgA1-IgG aggregate probe (Lab Invest, 66: 86-95), the relative significance of the asialoglycoprotein receptors in IgAIC clearance is still uncertain. EXPERIMENTAL DESIGN: The removal kinetics of 99mTc diethylenetriamine-pentaacetic acid-conjugated asialo alpha 1 acid glycoprotein (AAGP) and 123I-labeled IgA1-IgG aggregate were analyzed in 11 cirrhosis patients and 13 IgAN patients of comparable age. RESULTS: IgA1-IgG aggregate mean plasma clearance rate was delayed in IgA neuropathy (IgAN) patients (slope 0.038 minutes-1, range 0.027 to 0.053) compared with normals (0.047 minutes-1, range 0.038 to 0.053, p = 0.05). The liver was the main organ involved in the IgA1-IgG removal. When compared with normals, (34.3 minutes, range 29.8 to 42.2), the liver mean transit time (MTT) was significantly (p < 0.02) prolonged in IgAN patients (41.3 minutes, 33.6 to 52.3). Participation of spleen in clearance was observed in some patients and was almost invariably concurrent with normal clearance parameters. Conversely, 9 out of 11 cirrhosis patients had a remarkable splenic uptake, but the blood clearance rate was invariably delayed (0.022 minutes-1, 0.014 to 0.028, p < 0.003) and liver MTT extremely prolonged (122.4 minutes, 52.4 to 400, p < 0.003). In IgAN patients with delayed clearance of the IgA1-IgG aggregate, a distinct trend of progression towards renal failure was noted. AAGP clearance was also delayed in cirrhosis patients: slope = 0.166 minutes-1, 0.108 to 0.247, p = 0.05 as compared with both normals (0.230, 0.173 to 0.289) and IgAN patients (0.250, 0.184 to 0.254). Liver MTT in cirrhosis patients was extremely prolonged: 240.6 minutes, 132.5 to 400 minutes, p < 0.007 compared with both normals (90.0 minutes, 82.7 to 96.6) and IgA patients (92.2 minutes, 70.3 to 107.1). AAGP clearance parameters in normals and IgAN patients were not statistically different. MTT values of AAGP and IgA1-IgG aggregate were strictly related (p = 0.008), suggesting that asialoglycoprotein receptors are partially involved in the clearance of the IgA1-IgG aggregate probe. CONCLUSIONS: Some patients with IgAN have a prolonged circulation of an IgAIC miming probe, probably due to an impaired macrophage function. Other possibilities of prolonged circulation of IgAIC in these patients should imply an abnormal IgA glycosylation pattern that allows IC to escape from an effective asialoglycoprotein receptor system. In cirrhosis patients, all of the removal routes of IgA and IgA containing IC are greatly altered suggesting a causative role in the development of an associated, often clinically inapparent, glomerular disease.

Adult↗

PubMed1991

Combined evaluation of total and functional liver plasma flows and intrahepatic shunting.

A diagnostic protocol was studied, designed to evaluate the main parameters of liver circulation in man. A water solution of D-sorbitol (S) and indocyanine green (ICG) was infused intravenously in six controls and nine cirrhotics. Steady-state renal and hepatic S clearances as well as hepatic ICG clearance were calculated. In controls the values (mean +/- SD) of the independent measurements of S and ICG hepatic clearance were 978 +/- 107 and 519 +/- 142 ml/min, respectively, while in cirrhotic patients they were 554 +/- 238 and 231 +/- 90 ml/min. Owing to the kinetic properties of S, its hepatic clearance may be regarded as a measure of functional liver plasma flow (FLPF). The total liver plasma flow (TLPF) values (mean +/- SD), calculated according to Fick's principle, were 1091 +/- 157 ml/min (S method) and 1033 +/- 153 ml/min (ICG method) in controls, and 1251 +/- 554 and 1284 +/- 677 ml/min in cirrhotics. In controls, FLPF was found to be very close to TLPF. In cirrhotic patients the difference between TLPF and FLPF (ranging from 169 to 2093 ml/min when measured by S method) was considered as an approximate estimate of intrahepatic shunting. The procedure is safe and simple and may add a new dimension to the investigation of hepatic circulation.

Adult↗

PubMed1990

Educational applications of a knowledge-based expert system for medical decision making in hepatology.

An expert system for medical decision making in hepatology has been developed with the aim of assisting medical education. The knowledge representation is based on different slots respectively concerned with structural and protypical description, and system control. Reasoning is performed at two levels considering in sequence syndromes and diseases. Explanations are available at any time during the reasoning process. Educational facilities are provided by using the help sections of the system, which include definitions and descriptions of finding in both health and disease, as well as summaries defining essential clinical and pathophysiological features of all diagnostic hypotheses. The system provides the following educational functions: support to medical decision making, differential diagnosis, knowledge-base consultation, system description and clinical simulation. A good correspondence was found between the conclusions and suggestions provided by the system and those of the attending physicians. The program, which was written in PROLOG and developed under MS-DOS Operating System, runs on IBM-compatible personal computers equipped with hard-disk and mouse.

Computer Systems↗

PubMed1989

PEPTY: a knowledge-based program for assisting medical reasoning in peptic diseases.

PEPTY is a program developed with the aim of providing a diagnostic and therapeutic assistance in managing peptic diseases. Its theoretical basis is an accurate analysis of current concepts in peptic disease diagnosis and treatment. This was done by reviewing recent literature and consulting skilled gastroenterologists. The decision tree includes three sections dealing with diagnostic, therapeutic and monitoring problems. The diagnostic section starts by evaluating clinical data from patient history and physical examination; the diagnostic hypotheses given at this level are refined and eventually confirmed by further information in the following section. Here the decision tree becomes modular in that a proper therapeutic and monitoring pathway is defined for four disease classes: gastroduodenal peptic ulcer and duodenitis, gastro-oesophageal reflux, erosive gastritis, and chronic antral gastritis. In the therapeutic section a cost-benefit analysis of possible therapeutic choices is always performed, but the final decision is made by the user. Complications, side effects and treatment efficacy are also considered and the program finally suggests the appropriate maintenance treatment. Patient data display, storage and retrieval, and explanation facilities are supplied. The system can provide a 'second opinion' in the medical practice and may be a useful learning tool for medical students.

Artificial Intelligence↗

PubMed1987

Hepatic clearance of D-sorbitol. Noninvasive test for evaluating functional liver plasma flow.

The hepatic clearance of D-sorbitol, a natural polyol which is metabolized by the liver, was studied in normal and cirrhotic subjects after bolus intravenous injection (2 g) and during constant infusion (54 mg/min) with the aim of providing a noninvasive and simple measure of functional liver plasma flow. The high hepatic extraction of D-sorbitol and the dose-independence of its clearance pointed to a flow-dependent clearance regimen. The renal excretion was taken into account when computing the hepatic clearance. Day-to-day reproducibility of the test was good. No significant difference was found when the hepatic clearance was measured by bolus injection or constant infusion methods. As measured by the bolus injection method, the mean (+/- SD) hepatic clearance in the normal subjects (911 +/- 137 ml/min) was significantly greater (P less than 0.001) than that of the cirrhotics (456 +/- 181 ml/min).

Humans↗

PubMed1987

Non-invasive evaluation of portal-systemic shunting in man by D-sorbitol bioavailability.

Portal-systemic shunting is an important circulatory abnormality in patients with cirrhosis. This study explores the potential of the natural polyol D-sorbitol as test compound for non-invasive assessment of shunting. Ten normal subjects, 10 patients with cirrhosis and 12 cirrhotics with surgical portacaval shunts were studied after oral and intravenous administration of a 2 g dose of sorbitol. As measured by the H2 breath test, removal from the intestinal lumen was complete in both groups. Bioavailability of sorbitol, calculated as ratio of the areas under the plasma concentration/time curve after p.o. and i.v. administration, was zero in normal subjects, 0.29 +/- 0.15 in cirrhotic patients, and 0.38 +/- 0.11 in patients with portacaval shunts. Calculation of bioavailability on the basis of urinary outputs of sorbitol gave similar results. It is concluded that the bioavailability of sorbitol reflects portal-systemic shunting, although the relatively low figures suggest some degree of sorbitol metabolism by enterocytes.

Adult↗

PubMed1986

Sorbitol clearance: a parameter reflecting liver plasma flow in the rat.

According to the clearance concepts, the functional liver plasma flow may be directly measured from the plasma kinetics of any substance whose hepatic intrinsic clearance largely exceeds liver perfusion. The present study was designed to ascertain the requirements for the reliability of D-sorbitol plasma clearance in evaluating changes of liver perfusion in the male Wistar rat. The plasma disappearance curve of D-sorbitol (3 mg/100 g b.w. by bolus i.v. injection) followed a first order kinetics and fitted a two-compartment model. Very similar estimates of D-sorbitol plasma clearance were obtained by applying the area under the curve method to data obtained by the trapezoidal rule and by compartmental analysis. D-sorbitol hepatic extraction was almost complete in controls and in rats submitted to porta-caval shunt and hepatic artery ligation, while significantly decreased after partial hepatectomy. Renal output never exceeded 10% of the administered amount. No in-vivo diffusion into red cells was observed. In controls, the functional liver plasma flow, as measured by D-sorbitol clearance was 2.83 +/- 0.68 ml/min/100 g (mean +/- SD). Significantly lower values were found in rats submitted to porta-caval shunt (1.19 +/- 0.38), hepatic artery ligation (2.06 +/- 0.53), and partial hepatectomy (1.03 +/- 0.44).

Animals↗

PubMed1983

Pirenzepine does not impair liver blood flow in the rat.

The present study was performed with the aim of establishing whether the muscarinic-receptor antagonist pirenzepine impairs liver blood flow, as previously observed for H2-blockers. For this purpose, two different doses of pirenzepine (0.3 and 0.6 mg/100 g b.w. respectively) were administered to two groups of rats. Liver plasma flow was measured 30 min after treatment by the new sorbitol clearance test which is simple and does not require hepatic vein catheterization. The results were compared with those obtained in a control group and in a group treated with cimetidine. It was shown that, compared to the control group in which the observed functional liver plasma flow was 5.0 +/- 1.3 ml/min/100 g b.w. (MV +/- SD), rats treated with either dose of pirenzepine showed no significant impairment of liver perfusion. On the other hand, cimetidine treatment produced a significant reduction (p less than 0.001) of functional liver plasma flow. Our results show that pirenzepine treatment does not significantly impair liver functional activity through reduced liver perfusion. They also suggest that muscarinic receptors are probably not involved in the control of splanchnic blood flow.

Animals↗

PubMedDate not supplied

D-sorbitol plasma disappearance rate: an index to evaluate changes in liver circulation.

The hepatic clearance of D-sorbitol was proven to be a reliable parameter for evaluating the functional liver plasma flow. Twenty-five normal subjects and 50 cirrhotic patients were studied in order to assess if the measure of the plasma disappearance rate of sorbitol can be used as a simpler procedure to evaluate changes in liver perfusion and to predict modifications of drug bioavailability due to circulatory events. The plasma disappearance rate was calculated between 10 and 20 min after intravenous administration of a 2-g dose because in this time interval plasma levels were in the optimum range for the chemical assay, and the plasma concentration/time curve fitted a decreasing exponential function. Plasma disappearance rate values were found to correlate significantly (r = 0.666, p less than 0.001) with sorbitol hepatic clearance, as calculated after the 2-h test. The test had a good day-to-day reproducibility both in normal subjects and cirrhotic patients. In 5 patients submitted to surgical side-to-side portacaval shunt, decreases of plasma disappearance rate and sorbitol hepatic clearance showed no significant difference. Mean values (+/- SD) of D-sorbitol plasma disappearance rate were 0.048 +/- 0.014 min-1 in cirrhotic patients, and 0.081 +/- 0.014 min-1 in normal subjects (p less than 0.001).

Blood Flow Velocity↗

PubMedDate not supplied

Diagnostic value of prealbumin and retinol-binding protein in acute and chronic liver diseases.

Prealbumin (PA) and retinol-binding protein (RBP) serum concentrations have been determined in 161 patients with different chronic and acute liver diseases and in 49 healthy controls. Their possible role in clinical practice as liver markers of hepatic biosynthesis in comparison with other traditional tests: albumin, pseudocholinesterase and clotting factors II, VII and X associated activity (Hepato-Quick) was investigated. PA and RBP were always highly intercorrelated and significantly decreased in acute viral hepatitis, steatosis, chronic persistent and active hepatitis, cirrhosis, hepatic tumors and primary biliary cirrhosis. Among the different tests, PA and RBP presented the best values of specificity (0.98 and 0.97, respectively), sensitivity (0.77 and 0.73) and positive (0.99) and negative prediction (0.57 and 0.46). In chronic liver diseases PA and RBP distinguished more efficiently than the other biosynthetic markers among diseases with different degree of severity. In acute viral hepatitis the behavior of PA and RBP, followed for 4 consecutive weeks, was similar to that of Hepato-Quick and better than the other tests in reflecting the clinical course of the disease.

Acute Disease↗