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Biomedical subjects

G Molino

Publications and source records attributed to G Molino.

At least 37 records · Page 2Linked to original sources

Assessment of the hepatic circulation in humans: new concepts based on evidence derived from a D-sorbitol clearance method.

D-Sorbitol (SOR) is safe, is easy to measure, and has an exceptionally high extraction ratio in the normal liver of 0.93+/-0.05 (mean+/-SD). Together with the general interest in hepatic hemodynamics, these facts motivated us to review the usefulness of this compound for the assessment of liver plasma flow in humans. We concluded that in subjects without liver disease the nonrenal clearance of SOR-measured noninvasively-very closely approximates hepatic plasma flow. Because of its lower and more variable extraction ratio, indocyanine green should no longer be used without hepatic vein catheterization. Even in patients with cirrhosis, SOR exhibits higher hepatic extraction ratios than indocyanine green. To fully explore the potential of SOR in the evaluation of such patients attention needs to be paid to the complex changes in architecture and function occurring in this disease. In cirrhotics the noninvasively measured nonrenal clearance of SOR presumably approximates the flow through intact and capillarized sinusoids (functional flow) and reflects the amount of blood having functional contact with hepatocytes. The theoretic background of the method, its accuracy, further research needs, and potentials of various approaches are discussed in detail.

Coloring Agents↗

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↗

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↗

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↗

Hyperdynamic circulation in patients with cirrhosis: direct measurement of nitric oxide levels in hepatic and portal veins.

BACKGROUND/AIMS: Peripheral vasodilation represents the main vascular dysfunction associated with the hyperdynamic circulation of liver cirrhosis. This study was intended to measure directly regional and systemic levels of nitric oxide, a potent vasorelaxing mediator, in order to assess its role in the development of hemodynamic changes of cirrhosis. METHODS: We compared nitric oxide levels in the splanchinic and systemic circulation of 25 patients with cirrhosis undergoing transjugular intrahepatic portosystemic stent shunt and in the hepatic vein and peripheral blood of 10 patients without cirrhosis submitted to venous catheterization. Nitric oxide levels were measured through electron paramagnetic resonance spectroscopy as nitrosylhemoglobin complexes. RESULTS: Significantly higher nitric oxide levels were calculated in patients with cirrhosis with respect to controls, both in the peripheral and hepatic veins. In patients with cirrhosis, nitric oxide levels in the portal vein (3.44 +/- 2.17, expressed in arbitrary units) were higher than in the systemic circulation (1.89 +/- 1.15), but lower than in the hepatic vein (4.75 +/- 2.53; p < 0.001 by variance analysis). CONCLUSIONS: These data suggest that nitric oxide synthetic pathway activity as well as nitric oxide release are enhanced at the level of splanchnic vasculature and, more important, in the hepatic tissue, confirming evidence of the predominant role of nitric oxide in the pathogenesis of hemodynamic changes in patients with cirrhosis with portal hypertension.

Aged↗

Computerized approach to active and objective quality control of patient care.

The paper describes a quality control program based on the principles of clinical methodology and indicators defined by physicians and hospital administrators according to general as well as local needs. The program is supported by a knowledge-based system which can be used in two ways: with on-line helps and hints to ensure effective and efficient medical decisions on a simulated patient for training purposes; and without facilities supporting the user to be used on an on-line setting for performance evaluation. The quality control program includes the evaluation of effectiveness and efficiency of patient care with respect to the overall process, single hypotheses and individual decisions: the evaluation regards the number and reliability of activated hypotheses, costs, time spent, number and appropriateness of investigations. The overall process is recursive, in that the results of each cycle are used by physicians to define new goals and indicants for the next cycle; quality control is active because physicians under evaluation are directly involved in the definition of goals and indicants and in the evaluation of results; evaluation is objective because indicants are predefined, and evaluation criteria are transparent.

Artificial Intelligence↗

Assessment of functional liver mass and plasma flow in acromegaly before and after long-term treatment with octreotide.

Functional liver mass and functional liver plasma flow (FLPF) were assessed in 11 patients with clinical features of acromegaly by determining galactose elimination capacity (GEC) and extrarenal clearance of sorbitol, before and 5 to 7 months after treatment with the long-acting somatostatin analog, octreotide (150 to 600 micrograms/d in three subcutaneous injections). Growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels, as well as liver size by ultrasound, were also recorded. Baseline GEC was increased in every patient but one, for a mean of 0.78 +/- 0.10 g/min (normal, 0.53 +/- 0.07; P < .01). At reevaluation after 5 to 7 months of octreotide treatment, a significant reduction of GEC was observed (0.62 +/- 0.08 g/min, P < .001). Changes of GEC paralleled those of GH (38.6 +/- 34.4 v 11.7 +/- 15.2 micrograms/L, P < .01) and IGF-I (5.0 +/- 1.7 v 2.7 +/- 2.2 U/ml, P < .001). Significant correlations were found between GEC and GH (r = .50, P < .05) and between GEC and IGF-I (r = .55, P < .01). FLPF, assessed by extrarenal clearance of sorbitol, was within the normal limit in all cases (0.98 +/- 0.19 v 0.97 +/- 0.12 L/min, NS) and remained normal after 5 to 7 months of octreotide treatment (0.99 +/- 0.11 L/min). Hepatic structure determined with ultrasonic scanning and conventional liver-function tests were basally normal in all patients, with a slight increase of liver volume in three cases. No change of biochemical and/or morphological features occurred during follow-up evaluation. The results support the hypothesis that GH and especially IGF-I enhance liver metabolic capacity; conversely, functional liver perfusion is largely independent of their actions. Our data also suggest that octreotide is unable to produce well-structured changes of liver circulation when administered long-term.

Acromegaly↗

Prognostic value of the galactose test in predicting survival of patients with cirrhosis evaluated for liver transplantation. A prospective multicenter Italian study. AISF Group for the Study of Liver Transplantation. Associazione Italiana per lo Studio del Fegato.

AIMS/METHODS: The present study aimed to examine whether the galactose elimination capacity can be used to predict the survival of patients with advanced liver disease. We studied 194 patients with cirrhosis, belonging to Child class B and C, for 2 years each. RESULTS: The overall probability of survival was 79% at 6 months, 72% at 1 year and 62% at 2 years. Variables significantly associated with the duration of survival, as assessed by univariate analysis, were the Child-Pugh score, presence of ascites, size of esophageal varices, prothrombin time, albumin, bilirubin, urea, creatinine, glucose and galactose elimination capacity. By a multivariable analysis, only Pugh score (p = 0.005), creatinine (p < 0.001), varices (p = 0.001) and galactose elimination capacity (p < 0.001) were independent predictors of mortality. The galactose elimination capacity was even more sensitive when the end-point was limited to deaths due to liver failure and hepatorenal syndrome. A new score obtained by summing the Pugh score with a score derived from galactose elimination capacity was quite simple and accurate for predicting survival. CONCLUSIONS: The quantitative measurement of liver function as the galactose elimination capacity could be of use to identify patients with cirrhosis and probable short survival who might benefit most from urgent transplantation.

Adolescent↗

Determination of functional portal-systemic shunting in patients submitted to hepatic angiography.

Angiographic visualization of the hepatic vascular bed by selective angiography can be profitably complemented with the evaluation of functional portal-systemic shunting by D-sorbitol bioavailability. Seventeen patients requiring diagnostic arterial catheterization were studied: most of them had biopsy-proven liver cirrhosis. Patients were studied at rest and after overnight fasting on two subsequent days, in which a sterile pyrogen-free solution (1.5%) of D-sorbitol was administered by direct infusion (15 mg/min for 20 min) into the superior mesenteric artery and an antecubital vein, respectively. The fractional bioavailability (Fma) of D-sorbitol was calculated as the ratio between the net cumulative urinary outputs obtained after infusion through the catheter into the superior mesenteric artery and the systemic vein, respectively. A good correlation was found between the estimated fractional portal-systemic shunting, which in the present study ranged between 1.4% and 96.7%, and a suitable index scoring the clinical evidence of collateral circulation. Since the hepatic removal of D-sorbitol is not affected by sinusoidal capillarization and its hepatic extraction ratio is quite high and only slightly modified by reduction in the number or functional activity of hepatocytes, the measured Fma can be assumed as a parameter reflecting the entity of portal-systemic shunting. The test is safe and inexpensive, and appears potentially useful in several situations in which portal-systemic shunting is pathophysiologically relevant.

Adult↗

Computer-aided diagnosis in jaundice: comparison of knowledge-based and probabilistic approaches.

The study reported in this paper is aimed at evaluating the effectiveness of a knowledge-based expert system (ICTERUS) in diagnosing jaundiced patients, compared with a statistical system based on probabilistic concepts (TRIAL). The performances of both systems have been evaluated using the same set of data in the same number of patients. Both systems are spin-off products of the European project Euricterus, an EC-COMAC-BME Project designed to document the occurrence and diagnostic value of clinical findings in the clinical presentation of jaundice in Europe, and have been developed as decision-making tools for the identification of the cause of jaundice based only on clinical information and routine investigations. Two groups of jaundiced patients were studied, including 500 (retrospective sample) and 100 (prospective sample) subjects, respectively. All patients were independently submitted to both decision-support tools. The input of both systems was the data set agreed within the Euricterus Project. The performances of both systems were evaluated with respect to the reference diagnoses provided by experts on the basis of the full clinical documentation. Results indicate that both systems are clinically reliable, although the diagnostic prediction provided by the knowledge-based approach is slightly better.

Artificial Intelligence↗

Effects of nifedipine on functional liver plasma flow in normal subjects and in patients with cirrhosis.

The short-term effects of nifedipine (10 mg administered sublingually) on functional liver plasma flow, measured by calculating the extrarenal clearance of sorbitol, were investigated in 12 normal volunteers and 40 patients with cirrhosis scored according to Child-Pugh classification. Nifedipine significantly increased functional liver plasma flow in healthy subjects (23%, p < 0.0001) and in patients with cirrhosis in the Child-Pugh class A group (19%, p < 0.001); in patients in the Child-Pugh class B group functional liver plasma flow was not modified, whereas in the patients in the Child-Pugh class C group it was significantly reduced (-7%, p < 0.02). The mean arterial pressure showed a significant reduction in all groups studied. According to the pathophysiologic meaning of functional liver plasma flow, it is suggested that nifedipine meets criteria for an ideal test substance to evaluate the functional reserve of the liver. Furthermore, when used with the Child-Pugh classification, its effect on functional liver plasma flow may be useful to improve the efficiency of the Child-Pugh classification, in establishing the prognosis of patients with cirrhosis.

Adult↗

LIED--liver: information, education and diagnosis.

In this paper we describe LIED (Liver: Information, Education and Diagnosis), a diagnostic expert system devoted to medical education in the field of hepatology. LIED combines the facilities of a traditional expert system for clinical diagnosis with several modules designed for educational purposes. The goal of such modules is to train physicians, in particular as regards the improvement of their problem solving ability (at the end of their curricula students in medicine usually lack experience in organizing an efficient and accurate diagnostic process). Training on real and simulated cases has been widely recognized as a proper approach to clinical experience. The architecture of the diagnostic system is introduced, which forms the core of LIED, and which has been derived from our previous experience, and the various educational functions are discussed that were developed on top of the basic architecture.

Computer Simulation↗

Computer assisted development of diagnostic expert systems. A domain-independent package (EMPTY) for acquisition and use of expert's medical knowledge.

The package EMPTY has been developed with the aim of providing a tool based on well assessed methodological principles which can support both the organisation and use of medical knowledge for diagnostic and educational purposes. EMPTY is domain-independent and results in two interactive programs: ASK guides the acquisition of medical knowledge and RUN supports medical decision-making and provides facilities for medical education. The knowledge bases developed on ASK have a standard formal structure: they include taxonomies, definitions and descriptions of diseases, clinical findings and investigations; production rules for activation and refinement of diagnostic hypotheses; frame-like profiles of diseases; and quantitative criteria for scoring the clinical evidence on the base of available data.

Computer-Assisted Instruction↗

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↗

A computer-based approach to education and training in clinical gastroenterology.

Computer systems adapted to gastroenterology can effectively assist in organization of knowledge, clinical reasoning and competence, and manual skills. Computer-based methods and tools for medical education comprise systems for computer-assisted instruction (CAI), systems for clinical simulation (CS), and expert systems (ES). Computer-based methods in medical education are now so well defined and assessed that their use should be considered the necessary goal for coming years.

Computer-Assisted Instruction↗

Application of artificial intelligence techniques to a well defined clinical problem: jaundice diagnosis.

Jaundice is a very common medical condition, in which pathophysiological knowledge has been quite well assessed and clinical features are usually well known. However, incorrect conclusions are sometimes reached in medical practice which can lead to serious implications. Thus, jaundice diagnosis appears as one of the medical situations which might be substantially improved by computer assistance. The present study is aimed at describing and discussing in what way a computer program supporting medical decision making in jaundiced patients can be developed on the basis of advanced Artificial Intelligence methods. To this extent methodological problems concerned with the organization and the formalization of medical knowledge have been outlined with some detail. The resulting expert system is expected to become a well assessed and potentially useful tool for both medical decision making and medical education.

Algorithms↗

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↗

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↗