Bile acid malabsorption in progressive systemic sclerosis.
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Biomedical subjects
Publications and source records attributed to P Pazzi.
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The pH values in 203 patients with various gastroduodenal pathologies were measured by means of a glass electrode inserted into the bioptic channel of the gastroscope. Analysis of the results confirms what we know of pH variations in gastric or duodenal ulcer cases and shows where perendoscopic pH measurements may be used beneficially. In particular it was found that mucous pH is not affected by H2 antagonists if these are taken more that 12 hours before the examination. Perendoscopic pH measurement appears to be a valuable tool in screening stomach lesions at risk in cases of chronic gastritis, since it facilitates the identification of atrophic or metaplastic lesions.
Total bile acid concentrations were estimated in fasting serum samples from 251 patients with chronic liver disease and 108 controls without liver disease, together with conventional liver tests. Serum bile acids level was significantly higher in patients with liver disease than in control group. Fasting serum bile acid concentration was raised in 172 of the 251 patients with impaired hepatic function (68.5%). Only gamma-glutamyltranspeptidase and transaminase tests exhibited a higher abnormality frequency. Two-hour postprandial serum bile acid concentrations were measured in 78 patients: the meal test shows a rise in sensitivity (+26.9%). Our results confirm that serum bile acids concentration represent a sensitive and reproducible test for hepatobiliary disorders.
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This study reports the results of an evaluation of the effectiveness and tolerability of rifaximin, an intestinal topical antibiotic. It was administered using a nasogastric tube in patients with severe enterocolitis and bacterial superinfections causing intestinal inflammatory diseases and portosystemic encephalopathy. The drug proved highly effective clinically and produced neither local nor systemic side-effects.
Chronic liver diseases are potentially evolving clinical situations which, independently by the etiology, could proceed towards progressive liver structural and functional impairments. The only efficient treatment is orthotopic liver transplantation. Chronic liver diseases, and up to 40% of liver cirrhosis, are initially asymptomatic, but cirrhosis is the most frequent cause of death among non-neoplastic digestive diseases. Important elements complicating a decompensated liver cirrhosis are ascites, hepatic encephalopathy, digestive bleeding and jaundice. Acute liver failure (ALF) is the expression of a clinical state, that is common to many conditions sharing severe liver structural and functional impairments. In patients affected by decompensated liver cirrhosis, ALF could be triggered by several factors, while the death is caused by bleeding episodes, hepato-renal syndrome, spontaneous bacterial peritonitis or hepatocarcinoma. In patients affected by chronic liver diseases, the diagnosis of ALF is based on progressively increasing jaundice, encephalopathy and coagulopathy. Recent clinical trials have evaluated the efficacy of extrahepatic liver support systems, either artificial or bio-artificial, in treating episodes of ALF in chronic liver patients. The preliminary results indicate a potential use of such systems in blood detoxification, but they also showed limits in increasing patient survival.
Previous attempts in improving the outcome of acute liver failure patients were based on extracorporeal artificial systems such as hemodialysis, hemoperfusion, plasmaperfusion, hemoadsorbtion and plasma exchange. Despite more than 30 years of research and development in this field, an artificial liver has still not become a reality, since purely artificial support systems have shown only minor improvement in patient's survival, and orthotopic liver transplantation is the only effective cure. This review takes a critical look at past and present concepts for an artificial liver support system, evaluating the advantages and disadvantages of the aforementioned techniques. Progress in methods and techniques for maintaining long-term hepatocyte culture in vitro indicate the potential use of isolated liver cells in bioartificial liver support systems. Recent studies suggest the use of traditional artificial liver support systems, such as hemoadsorbtion or plasma-absorbtion on activated charcoal particles or synthetic ion-exchange or neutral resins to improve and prolong the efficiency of the so-called hybrid or bioartificial liver, in which isolated hepatocytes are used.
Isolated hepatocytes in culture represent an idoneous system for the study of liver physiology and metabolism. Furthermore, they are also widely utilized in pharmacological and toxicological study, in evaluating xenobiotic substance effects on the liver. In this paper, we reviewed the enzymatic methods for liver cell isolation in some mammalian species, as well as the techniques for qualitative and quantitative evaluation of cell number, vitality, purity, morphology and function. Recently, there has been a renewed interest in hepatocyte transplantation and hepatocyte-based liver support systems. From a clinical point of view, isolated hepatocytes could be useful in temporarily substituting an acutely damaged liver, a liver affected by a chronic pathology, or to correct an inherited liver disease carrying a severe metabolic derangement. Early experimental results of allogeneic hepatocyte transplantation, as well as the first clinical trials of bioartificial liver support systems employing xenogeneic hepatocytes are promising and contribute to maintain that interest in liver cell isolation and purification methods.
Hepatocyte based artificial liver support systems are under investigation to support acute liver failure patients. The main purpose of such systems is to serve as a bridge to liver transplantation, or to promote spontaneous liver recovery. Limitation in mass-transfer capacity makes hollow-fiber bioreactors unsuited for long-term functioning of hybrid devices. We developed a novel radial-flow bioreactor in which the fluid perfuses the module from the center to the periphery, after having diffused through a space occupied by a three-dimensional structure filled with the hepatocytes. Five grams of freshly isolated porcine hepatocytes were seeded into uncoated, woven-non woven, hydrophilic polyester fabric, overlaid by two polyethersulfone membranes. Liver cells were perfused with 37 degrees C-warm, oxygenated, serum-free tissue culture medium, in which NH4Cl and Lidocaine were added at the final concentration of 1 mM and 60 micrograms/ml, respectively. Ammonium chloride removal, urea synthesis, monoethylglycinexylide (MEGX), pO2, pCO2, and pH were measured throughout the 14 day duration of the study. In a separate set of experiments, a scaled-up version of the radial flow bioreactor containing 150 grams of cells was perfused for 7 h with recirculating human plasma and MEGX production was monitored. During the 2 weeks of the study, an increasing production of urea was paralleled by constant ammonium removal. MEGX concentration after Lidocaine addition increased throughout the 14 days of perfusion with tissue culture medium, as well as after 7 hour perfusion with human plasma. Under transmission and scanning electron microscopy cells appeared attached to the polyester and one to each other, displaying ultrastructural features typical of functioning hepatocytes. Our study showed that liver cells were metabolically active when perfused into the radial-flow bioreactor. This configuration allowed close contact between media, or plasma, and cells at a physiological flow rate, by equalizing the concentration of the perfusing components, including O2, throughout the module. Our results suggest a potential use of this system for temporary extracorporeal liver support in acute hepatic failure patients.
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