P. Pazzi

OBJECTIVES A previous single-country pilot study indicated serum anti-GM2 and anti-GA1 anti-glycolipid antibodies as potential biomarkers for acute canine polyradiculoneuritis. This study aims to validate these findings in a large geographically heterogenous cohort. MATERIALS AND METHODS Sera from 175 dogs clinically diagnosed with acute canine polyradiculoneuritis, 112 dogs with other peripheral nerve, cranial nerve or neuromuscular disorders and 226 neurologically normal dogs were screened for anti-glycolipid antibodies against 11 common glycolipid targets to determine the immunoglobulin G anti-glycolipid antibodies with the highest combined sensitivity and specificity for acute canine polyradiculoneuritis. RESULTS Anti-GM2 anti-glycolipid antibodies reached the highest combined sensitivity and specificity (sensitivity: 65.1%, 95% confidence interval 57.6 to 72.2%; specificity: 90.2%, 95% confidence interval 83.1 to 95.0%), followed by anti-GalNAc-GD1a anti-glycolipid antibodies (sensitivity: 61.7%, 95% confidence interval 54.1 to 68.9%; specificity: 89.3%, 95% confidence interval 82.0 to 94.3%) and these anti-glycolipid antibodies were frequently present concomitantly. Anti-GA1 anti-glycolipid antibodies were detected in both acute canine polyradiculoneuritis and control animals. Both for anti-GM2 and anti-GalNAc-GD1a anti-glycolipid antibodies, sex was found a significantly associated factor with a female to male odds ratio of 2.55 (P=0.0096) and 3.00 (P=0.0198), respectively. Anti-GalNAc-GD1a anti-glycolipid antibodies were more commonly observed in dogs unable to walk (odds ratio 4.56; P=0.0076). CLINICAL SIGNIFICANCE Anti-GM2 and anti-GalNAc-GD1a immunoglobulin G anti-glycolipid antibodies represent serum biomarkers for acute canine polyradiculoneuritis.

To assess the efficacy of misoprostol for the treatment of chronic erosive gastritis and associated symptoms. We performed a double-blind controlled trial, administering 200-micrograms misoprostol tablets or placebo twice daily for 2 months to 48 patients with symptomatic chronic erosive gastritis. Symptomatology was assessed by means of a standard questionnaire at the beginning and at the end of the study, as well as endoscopic and histologic changes of the gastric mucosa. At the end of the treatment period, a significant reduction in symptom score was observed in misoprostol-treated (from 86.6 +/- 66.2 to 17.6 +/- 18.2, p < 0.001) but not in placebo-treated patients. Endoscopic score was significantly reduced at the end of the treatment period in the misoprostol group, compared with that of the placebo group (p < 0.05). A significant reduction in the activity of histologic gastritis was observed only in patients on misoprostol. The prevalence of gastric colonization by Helic...

There is much evidence to support the association between pigmentary cholelithiasis and chronic haemolytic anaemias [1–5], including prosthetic heart valve-induced haemolysis [6]. In this which is a former malaria district over 10% of the population is formed by heterozygotes with β-thalassaemia trait. However, this being a condition which is found all over the world, it is possible to calculate that there are no fewer than 5 million carriers of the thalassaemic trait in the Mediterranean area alone [7].

We investigated in vitro and in vivo the ability of a non-ionic adsorbing resin (styrenedivinylbenzene copolymer) to remove bilirubin and bile acids from human plasma. In preliminary experiments, human plasma from healthy donors, enriched in conjugated bile acids and bilirubin, and pooled plasma from jaundiced patients were recirculated through the resin column. The removal of bilirubin and bile acids was evaluated at two different flow rates (200 ml/min and 40 ml/min), and compared to an activated charcoal column. Four patients with severe jaundice were subsequently treated by 4-hour plasmaperfusion through the resin. The in vitro studies showed that after 1 hour the removal of bile acids was almost complete and bilirubin level decreased significantly, reaching a plateau after 4 hours. In the in vivo study, all treatments were well tolerated. After plasmaperfusion, serum bile acid levels decreased by 64.9–94.6% and total bilirubin by 35.3–57.7%. No clinical or biochemical side effe...

Aging and female sex are major risk factors for cholesterol gallstones: in addition to hepatic secretion of lithogenic bile, decreased gallbladder contractility may play a role in such physiological conditions. This study was aimed at evaluating the effect of age and sex on gallbladder kinetics in healthy subjects. Gallbladder volume was measured on the US images of 157 fasting subjects using the sum-of-cylinders method. No significant difference was observed between males and females. On the contrary, age was shown to have a significant positive correlation with fasting gallbladder volume, particularly in males. In a second group of 63 healthy volunteers gallbladder volumes were evaluated both before and after a standard meal. The subjects were grouped according to age, and fasting gallbladder volume appeared to be significantly greater in the groups formed by older people. Gallbladder volumes were compared in younger groups (under 35), and gallbladder emptying resulted to be much ...

We report two cases of unexplained hyperkalaemia during infusion of amino acid solutions enriched with branched chain amino acids. The increase in potassium levels developed 24 hours after starting infusion and normalization was obtained within 24 hours after stopping infusion. Acidosis, acute renal failure, concomitant cell destruction and haemolysis were excluded; antialdosteronic diuretics were not given. The authors hypothesize that hyperkalaemia could be due to a sudden increase in plasmatic osmolality caused by the hyperosmolarity (900 mOsm/l) of the solution, not counterbalanced by adequate ADH release owing to malfunctioning of hypothalamic osmoreceptors. At present this hypothesis is lacking in experimental proofs.

Data on the efficacy of Peg-interferon/ribavirin therapy for chronic hepatitis C are mostly derived from treatment of selected patients enrolled in clinical trials. This study aimed to assess the effectiveness of Peg-interferon/ribavirin therapy in "real world" chronic hepatitis C patients in Italy. Independent observational multicentre study including consecutive patients receiving Peg-interferon/ribavirin in the 18 months before (retrospective phase) and after (prospective phase) the start of the study. 4176 patients were eligible. The final study population consisted of 2051 patients in the retrospective and 2073 in the prospective phase. Sustained virological response was achieved by 1036 patients (50.5%) during the retrospective phase: 325 were genotypes 1/4 (34.1%) and 684 were genotypes 2/3 (67.2%) and by 800 patients (38.6%) during the prospective phase: 300 were genotypes 1/4 (28.4%) and 473 were genotypes 2/3 (51.5%). During multivariate analysis genotypes 2/3 were significantly associated with higher sustained virological response rates; cirrhosis and γ-glutamil-transpeptidase >2 times the normal limit were associated with poorer response. The response to Peg-interferon/ribavirin therapy in…

Recently, researchers have focused on the use of bioartificial liver (BAL) to support patients with fulminant hepatic failure (FHF). We have developed a cell-based BAL, consisting of porcine hepatocytes in a hollow-fiber bioreactor. To better characterize BAL metabolic functions in vitro, bioreactors were inoculated with 48-h-cultured, microcarrier-attached hepatocytes and perifused with recirculating human plasma that contained either 1 microCi of [24-14C] plasma-enriched cholate or 1 microCi of [24-14C] plasma-enriched taurocholate. Bile acids were sampled hourly and separated into four fractions (unconjugated, glycoconjugated, tauroconjugated, and sulfated) for radioactivity determination. Following 3 h perifusion, the glycoconjugated and sulfated bile acid fractions in the bioreactor extrafiber space were significantly elevated when compared to the recirculating plasma. During perifusion with taurocholate-enriched plasma, a relative decrease in the tauroconjugated fraction and an increase in the glycoconjugated fraction were observed. Cholate was accumulated by hepatocytes to a level threefold lower than taurocholate; however, a significant proportion of radioactivity (<25%) was detected in the glycoconjugated fraction. Ultrastructural examination of microcarrier-attached hepatocytes illustrated that the features typical of metabolically active liver cells were maintained. Our data demonstrate the ability of BAL to clear bile acids from the circulation, to accumulate cholate and taurocholate, and to conjugate a substantial amount of cholic acid.

Biliary sludge is a mixture of particulate matter which has precipitated from bile. It generally consists of cholesterol monohydrate crystals, calcium bilirubinate or other calcium salts. In a clinical setting, biliary sludge is almost always an ultrasonographic diagnosis. Although it is less clinically applicable, direct microscopic examination of gallbladder bile is far more sensitive than ultrasonography into sludge detection, and has to be regarded as the diagnostic gold standard. The overall prevalence of sludge in the general population is relatively low. However, several clinical conditions are associated with a particularly high prevalence of biliary sludge, including pregnancy, rapid weight loss, total parenteral nutrition, octreotide therapy, bone marrow or solid organ transplantation. The clinical course of biliary sludge varies, and complete resolution, a waxing and waning course, and progression to gallstones are all possible outcomes. It may cause complications usually...

Orthotopic liver transplantation (OLT) is the only effective therapeutic modality in severe acute hepatic failure (AHF). The scarcity of organs for transplantation leads to an urgent necessity for temporary liver support treatments in AHF patients. A hepatocyte-based bioartificial liver (BAL) is under investigation with the main purpose to serve as bridging treatment until a liver becomes available for OLT, or to promote spontaneous liver regeneration. We developed a novel radial-flow bioreactor (RFB) for three-dimensional, high-density hepatocyte culture and an integrated pumping apparatus in which, after plasmapheresis, the patient's plasma is recirculated through the hepatocyte-filled RFB. Two hundred thirty grams of freshly isolated porcine hepatocytes were loaded into the RFB for clinical liver support treatment. The BAL system was used 8 times in supporting 7 AHF patients in grade III-IV coma, all waiting for an urgent OLT. Three patients with no history of previous liver ...

... Update on Helicobacter pylori research. Diagnosis. Klein PD, Logan RP, Amarri S, Andriulli A, Iaquinto G, Luzza F, Pajarès Garcia JM, Pazzi P, Perri F, Pozzato P, Roda A, Vaira D, Zagari RM. PMID: 9222737 [PubMed - indexed for MEDLINE]. Publication Types: Congresses. ...

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 s...

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 empl...

A simple method for the assay of biliary lipids was used for routine determination of biliary cholesterol saturation index (CSI) in 17 healthy subjects, 40 untreated patients with radiolucent gallstones and 21 gallstone patients treated with ursodiol. The method is based on collection of bile with the Entero-Test, a device for easy sampling of gastrointestinal contents. The procedure was easy to perform and well accepted by the patients. Both CSI and the cholesterol content of bile were higher in untreated gallstone patients than in controls, and were significantly lower in treated than in untreated patients. Normal CSI was found in 35% of untreated gallstone patients, while 24% of healthy subjects had supersaturated bile. Supersaturated bile was still present in 14% of ursodeoxycholic acid treated patients, suggesting inefficacy of therapy. These results demonstrate the possibility of performing easy, routine determination of biliary lipid composition, which can yield useful inform...

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.

Since the exact mechanisms of the pathogenicity of Campylobacter pylori are not known, we performed an ultrastructural study with the aim of focusing on patterns of possible physical contact between C. pylori and gastric epithelium, and of considering them in relation to the bacterial pathogenicity. Among 20 random consecutive patients referred for routine gastroscopy, we studied ultrathin sections from the 11 patients with Campylobacter-like organisms, and recognized three patterns of physical contact between bacteria and epithelial cells. These patterns seem in accord with published data of C. pylori toxicity, and they could represent different evolutive stages of the infection.

A histological study was performed in order to evaluate the prevalence of Campylobacter-like organisms (CLO) and gastric antral lesions in 85 rheumatoid arthritis (RA) patients using NSAIDs, and in 100 nonrheumatoid outpatients comparable in terms of sex and age, not using NSAIDs. Histological evidence of gastritis was a common finding both in RA patients (88.2%) and in nonrheumatoid outpatients (89.0%). On the other hand, CLO were detected in a significantly lower proportion (p less than 0.001) of RA patients than outpatients (30.6 and 59.0%, respectively). Considering each NSAID used separately (aspirin, diclofenac sodium and ketoprofen), no significant difference in the presence of CLO in the three groups was found; in the small group of patients treated with aspirin, however, bacteria were never detected. MICs of each NSAID used against 15 isolates of Campylobacter pylori were also determined.