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Biomedical subjects

P Pazzi

Publications and source records attributed to P Pazzi.

At least 19 recordsLinked to original sources
PubMed2003

Biliary sludge: the sluggish gallbladder.

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 associated with gallstones, such as biliary colic, acute cholecystitis, and acute pancreatitis. The main pathogenic mechanism involved in sludge formation is probably gallbladder dismotility, and in selected patients measures aimed to maintain adequate gallbladder contractions has been shown to effectively prevent sludge development.

Bile↗
PubMed2002

Serum bile acids in patients with liver failure supported with a bioartificial liver.

BACKGROUND: Serum bile acids are increased in liver failure, but the composition of the bile acid pool in this condition has not been studied in detail. This information is of interest because of dihydroxy bile acid toxicity. METHODS: We measured serum bile acids by gas chromatography-mass spectrometry in 13 patients with fulminant liver failure and five patients with acute-on-chronic liver failure. Furthermore, serum bile acids were analysed in the same patients after 6 h of treatment with a bioartificial liver, consisting of a hollow-fibre cartridge with microcarrier-attached porcine hepatocytes and a charcoal column. RESULTS: Pre-bioartificial liver serum bile acids demonstrated a high dihydroxy/trihydroxy ratio and were higher in patients with acute-on-chronic liver failure than in those with fulminant liver failure (452.8 +/- 98.6 vs. 182.1 +/- 39.7 micro mol/L; P < 0.05). Bioartificial liver treatment decreased significantly serum bile acids in patients with fulminant liver failure (-38.8%) and acute-on-chronic liver failure (-35.8%), with a decreased dihydroxy/trihydroxy ratio. In vitro, porcine hepatocytes in the bioreactor cleared most conjugated bile acid species from pooled patient plasma. CONCLUSIONS: Acute liver failure is associated with very high serum levels of toxic bile acids that could contribute to the pathogenesis of the syndrome. Bioartificial liver treatment reduces both serum bile acid concentrations and the hydrophobicity of the bile acid pool.

Adolescent↗
PubMed2002

Early experiences with a porcine hepatocyte-based bioartificial liver in acute hepatic failure patients.

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 diseases were affected by fulminant hepatic failure (FHF) due to hepatitis B virus, 3 by primary non-function (PNF) of the transplanted liver, and one by AHF due to previous abdominal trauma and liver surgery. Six out of 7 patients underwent OLT following BAL treatment(s), which lasted 6-24 hours. All patients tolerated the procedures well, as shown by an improvement in the level of encephalopathy, a decrease in serum ammonia, transaminases and an amelioration of the prothrombin time, with full neurological recovery after OLT Our initial clinical experience confirms the safety of this BAL configuration and suggests its clinical efficacy as a temporary liver support system in AHF patients.

Adolescent↗
PubMed2002

Biologic liver support: optimal cell source and mass.

Hepatic support is indicated in acute liver failure (ALF) patients to foster liver regeneration, or until a liver becomes available for orthotopic liver transplantation (OLT), in primary non function of the transplanted liver, and hopefully in chronic liver disease patients affected by ALF episodes, in whom OLT is not a therapeutic option. The concept of bioartificial liver (BAL) is based on the assumption that only the hepatocytes can perform the whole spectrum of biotransformation functions, which are needed to prevent hepatic encephalopathy, coma and cerebral edema. Among others, two important issues are related to BAL development: 1) the choice of the cellular component; 2) the cell mass needed to perform an adequate BAL treatment. Primary hepatocytes, of human or animal origin, should be considered the first choice because they express highly differentiated functions. Accordingly, a minimal cell mass corresponding to 10% of a human adult liver, i.e. 150 grams of freshly isolated, > or = 90% viable hepatocytes should be used. When 4 degrees C cold-stored or cryopreserved hepatocytes are used, the cellular mass should be increased because of a drop in cell viability and function. In case of hepatoma-derived cells, cultured cell lines or engineered cells, an adequate functional cell mass should be used, expressing metabolic and biotransformation activities comparable to those of primary hepatocytes. Finally, the use of porcine hepatocytes or other animal cells in BAL devices should be presently directed only to ALF patients as a bridge treatment to OLT, because of potential transmission of animal retrovirus and prions which may potentially cause major pandemics.

Animals↗
PubMed2001

Appropriateness of upper gastrointestinal endoscopy: a hospital-based study.

Aims of this study were to evaluate: (1) whether upper gastrointestinal endoscopy (UGE) is used appropriately according to the American Society for Gastrointestinal Endoscopy (ASGE) and British Society of Gastroenterology (BSG) guidelines in a hospital setting and (2) whether there is any relationship between appropriateness of UGE and the presence of lesions detected by endoscopy. Indications and endoscopic findings for 734 consecutive UGE performed in 697 inpatients were retrospectively evaluated using ASGE and BSG guidelines to determine appropriateness of referrals. UGE showing endoscopic findings that had direct therapeutic or prognostic consequences were classified as "positive"; the other UGEs were classified as "negative." In all, 46% of UGEs were "positive," 54% "negative," and 61.7% and 23.2% of UGEs were inappropriate according to ASGE and BSG guidelines, respectively (P < 0.001). The probability of finding a positive endoscopy was significantly higher in UGE rated as appropriate than in those rated as inappropriate on the basis of ASGE guidelines (P < 0.001), but not on the basis of BSG guidelines. Endoscopies rated as inappropriate according to ASGE and BSG criteria showed a positive finding in 37.3% and 42.3% of cases, respectively (not significant difference). Multivariate analysis showed that the positive finding is directly related to age (P < 0.05), male gender (P < 0.001), prior UGE (P < 0.05), hematemesis (P < 0.001), and inversely related with upper abdominal pain (P < 0.01) and dyspepsia (P < 0.05). In hospitalized patients, UGE is frequently used for inappropriate indications, according to both ASGE and BSG guidelines. However, the actual clinical usefulness of appropriateness criteria, such as those proposed by ASGE and BSG, is questionable, as their strict observance could lead to missing a large number of significant endoscopic findings.

Adult↗
PubMed2001

Ursodeoxycholic acid alone or with chenodeoxycholic acid for dissolution of cholesterol gallstones: a randomized multicentre trial. The British-Italian Gallstone Study group.

BACKGROUND: Combination therapy using ursodeoxycholic acid plus chenodeoxycholic acid has been advocated for dissolution of cholesterol gallstones because the two bile acids have complementary effects on biliary lipid metabolism and cholesterol solubilization. AIM: To compare the clinical efficacy of combination therapy with ursodeoxycholic acid monotherapy. PATIENTS AND METHODS: A total of 154 symptomatic patients with radiolucent stones (< or = 15 mm) in functioning gallbladders were enrolled from six centres in England and Italy. They were randomized to either a combination of chenodeoxycholic acid plus ursodeoxycholic acid (5 mg.day/kg each) or to ursodeoxycholic acid alone (10 mg.day/kg). Dissolution was assessed by 6-monthly oral cholecystography and ultrasonography for up to 24 months. RESULTS: Both regimens reduced the frequency of biliary pain and there was no significant difference between them in terms of side-effects or dropout rate. Complete gallstone dissolution on an intention-to-treat basis was similar at all time intervals. At 24 months this was 28% with ursodeoxycholic acid alone and 30% with combination therapy. The mean dissolution rates at 6 and 12 months were 47% and 59% with ursodeoxycholic acid, and 44% and 59% with combination therapy, respectively. CONCLUSION: There is no substantial difference in the efficacy of combined ursodeoxycholic acid and chenodeoxycholic acid and that of ursodeoxycholic acid alone in terms of gallstone dissolution rate, complete gallstone dissolution, or relief of biliary pain.

Adult↗
PubMed2001

Long-term expression of highly differentiated functions by isolated porcine hepatocytes perfused in a radial-flow bioreactor.

To overcome the limitations of standard hollow-fiber module in ensuring efficient cell perfusion and long-term expression of highly differentiated hepatocyte functions, we developed a novel bioreactor in which a three-dimensional hepatocyte culture system was perfused in radial-flow geometry. Isolated porcine hepatocytes were cultured for 2 weeks in recirculating serum-free tissue culture medium, in which NH4Cl and lidocaine were repeatedly added, and ammonia removal, urea synthesis, monoethylglycinexylide (MEGX) production, albumin secretion, Po2, Pco2, O2 consumption, and pH were measured thereafter. During the whole duration of the study, ammonia removal was paralleled by urea production, while MEGX concentration was constantly increased. Our results indicated that hepatocytes remained differentiated and metabolically active throughout the duration of the study. The radial-flow bioreactor allowed physiological contact between recirculating fluid and cells by equalizing the concentration of the perfusing components, including O2, throughout the module, suggesting a potential use of this configuration for extracorporeal liver support.

Albumins↗
PubMed2000

Massive bleeding in an adult patient suffering from Meckel's diverticulum.

The case of a 22-year-old male who bled from a Meckel's diverticulum is described. The diagnosis was achieved after 99mTechnetium pertechnetate scintigraphy. With the administration of somatostatin very clear images were obtained. The histological examination confirmed the presence of ectopic gastric mucosa. The literature, over the last 10 years, has been reviewed to identify factors associated with bleeding in adults. Ectopic gastric mucosa is the most important factor predicting bleeding. The diagnostic approach to bleeding Meckel's diverticulum and the improvement in the quality of 99mTechnetium pertechnetate scintigraphy, following administration of somatostatin, is discussed.

Adult↗
PubMed2000

Review article: gall-bladder motor function in diabetes mellitus.

Although some controversy exists, diabetic patients generally are thought to have a two- to threefold increased risk of cholesterol gallstones. From previous studies there is no convincing evidence for a supersaturated bile in diabetics, whereas several reports indicate that impaired gall-bladder emptying could be one of the important factors in the increased incidence of gallstones in diabetics. However, studies of gall-bladder motility in diabetics have yielded conflicting results, probably because of substantial heterogeneity in the patients studied, emptying stimulus and technique used to assess gall-bladder motor function. The mechanism of the gall-bladder emptying abnormality in diabetics is not completely understood, although it has been proposed that it could represent a manifestation of denervation caused by visceral neuropathy. Based on normal post-prandial cholecystokinin release, it can be ruled out that impaired cholecystokinin release is the mechanism responsible for reduced gall-bladder emptying in diabetics. Other possible explanations for impaired gall-bladder contraction in diabetics include a decreased sensitivity of the smooth muscle of the gall-bladder to plasma cholecystokinin, and/or decreased cholecystokinin receptors on the gall-bladder wall.

Cholecystokinin↗
PubMed2000

Risk factors for the development of gallstone recurrence following medical dissolution. The British-Italian Gallstone Study Group.

OBJECTIVE: To assess risk factors for gallstone recurrence following non-surgical treatment. DESIGN: A prospective follow-up of a multicentre cohort of post-dissolution gallstone patients. SETTING: Six gastroenterology units in the UK and Italy. PARTICIPANTS: One hundred and sixty-three patients with confirmed gallstone dissolution following non-surgical therapy (bile acids or lithotripsy plus bile acids), followed up by ultrasound scan and clinical assessment at 6-monthly intervals for up to 6 years (median, 25 months; range, 6-70 months). OUTCOME MEASURES: Subject-related variables (sex, age, height, weight, body mass index), gallstone-related variables (number, diameter, presence of symptoms, months to complete stone clearance), treatment modalities (bile acid therapy, extracorporeal shock wave lithotripsy) and follow-up related variables (weight change, use of non-steroidal anti-inflammatory agents, statins, pregnancies and/or use of oestrogens) were assessed by univariate and multivariate analysis as putative risk factors for gallstone recurrence. RESULTS: Forty-five gallstone recurrences were observed during the follow-up period. Multiple primary gallstones and length of time to achieve gallstone dissolution were the only variables associated with a significant increase in the recurrence rate. Appearance of biliary sludge during follow-up was also significantly related to development of gallstone recurrence. Use of statins or non-steroidal anti-inflammatory agents did not confer protection against recurrence. CONCLUSIONS: Patients with primary single stones are the best candidates for non-surgical treatment of gallstones, because of a low risk of gallstone recurrence. The positive association of recurrence with biliary sludge formation and time to dissolution of primary stones may provide indirect confirmation for the role of impaired gallbladder motility in the pathogenesis of this condition.

Adolescent↗
PubMed2000

Postprandial refilling and turnover: specific gallbladder motor function defects in patients with gallstone recurrence.

BACKGROUND AND AIMS: Impaired gallbladder motor functions are important in the pathogenesis of primary cholesterol gallstones, and possibly in the pathogenesis of recurrent gallstones. By using ultrasonography and cholescintigraphy simultaneously, we recently defined new parameters of gallbladder motor function (postprandial refilling and turnover in addition to emptying), which were markedly impaired in gallstone patients. The aim of this study was to assess the value of these new parameters in distinguishing patients with from those without gallstone recurrence. METHODS: We studied 11 patients with gallstone recurrence, 11 without gallstone recurrence (at least 40 months after complete dissolution by oral bile acids) and 11 healthy controls. Simultaneous measurements of gallbladder volume (ultrasound) and gallbladder counts (gamma-camera scintigraphy) were carried out in the fasting state and at 10 min intervals following meal ingestion, for a period of 90 min. Gallbladder refilling, turnover of bile and turnover index were calculated, as well as gallbladder emptying by both cholescintigraphy and ultrasound. RESULTS: Patients with gallstone recurrence had reductions in gallbladder emptying, postprandial refilling and gallbladder bile turnover. They also had a significant reduction in the turnover index (1.7 +/- 1.4) compared to controls (3.5 +/- 0.3, P < 0.01) and to patients without gallstone recurrence (3.1 +/- 1.5, P < 0.05). Patients without gallstone recurrence had only a small reduction in emptying and no reduction in postprandial refilling or turnover compared to controls. CONCLUSIONS: We conclude that impairment of gallbladder emptying persists in all patients after gallstone dissolution, albeit to a more pronounced extent in patients with recurrence; but that impairment of postprandial refilling and turnover are specific defects in patients with recurrence.

Adult↗
PubMed2000

Validation of the 13C-urea breath test for the diagnosis of Helicobacter pylori infection in children: a multicenter study.

OBJECTIVE: The 13C-urea breath test (13C-UBT) is a safe, noninvasive, and accurate test for the detection of Helicobacter pylori (H. pylori) infection in adults. The aim of this study was to evaluate sensitivity and specificity of 13C-UBT in children using different types of test meal, doses of 13C-urea and breath sampling intervals. As yet, a validated, standardized 13C-UBT protocol for children has not been formulated. METHODS: 13C-UBT was performed in 115 children and repeated within 3 days, modifying the test meal or the dose of 13C-urea. H. pylori status was assessed by histology and rapid urease test. 13C-UBT was performed using 100 mg or 50 mg of 13C-urea and a fatty test meal (100 FA; 50 FA), 50 mg of 13C-urea, and a carbohydrate test meal (50 CA). Breath samples were collected every 10 min for 60 min. RESULTS: The 13C-UBT in children was highly sensitive and specific with all three protocols used. The best combination of sensitivity (97.92%) and specificity (97.96%) was obtained with Protocol 50 FA at 30 min with a cut-off of 3.5 per mil. CONCLUSIONS: The 13C-UBT is an accurate test for the detection of H. pylori infection also in children. Administration of 50 mg of 13C-urea, a fatty test meal, and breath sampling at 30 min appears to be the most convenient protocol.

Adolescent↗
PubMed2000

Enhancement of ursodeoxycholic acid bioavailability by cross-linked sodium carboxymethyl cellulose.

The bioavailability of ursodeoxycholic acid from a new formulation based on drug-loaded cross-linked sodium carboxymethyl cellulose was studied in man. The plasma levels of ursodeoxycholic acid were determined by gas chromatography-mass spectrometry after derivatization and sample purification by solid-phase extraction. Capsules containing the drug/polymer system were prepared and compared with conventional commercial ursodeoxycholic acid capsules after single oral administration using a randomized crossover experimental design. Although the drug/polymer system improved the in-vitro dissolution rate of ursodeoxycholic acid in simulated intestinal fluid, statistical evaluation of the area under the plasma concentration curves indicated no significant difference in the extent of bioavailability between the two formulations (14.93+/-4.43 vs 14.95+/-5.79 microM h; P > 0.2). However, following the administration of the ursodeoxycholic acid/cross-linked sodium carboxymethyl cellulose system with an enteric-coated capsule, the mean area under the plasma concentration curve (27.60+/-10.11 microM h) was significantly higher than that obtained after treatment with the commercially available ursodeoxycholic acid capsule (16.24+/-8-38 microM h; P < 0.05). We concluded that improved intestinal absorption of the drug was obtained with enteric-coated capsules filled with the ursodeoxycholic acid/polymer system. Moreover, the simplicity of the preparation and the non-toxicity of the polymer used as the carrier represented additional advantages of this dosage form.

Adult↗
PubMed2000

Evaluation of ursodeoxycholic acid bioavailability from immediate- and sustained-release preparations using gas chromatography-mass spectrometry and high-performance liquid chromatography.

An improved procedure is presented for the determination of ursodeoxycholic acid (CAS 128-13-2, UDCA) in human plasma and bile after oral administration of UDCA-containing dosage forms. The plasma samples after solid-phase extraction with silica-based C18- and strong anion exchange cartridges were assayed by gas chromatography-mass spectrometry (GC-MS) using selected-ion monitoring. The hexafluoroisopropyl trifluoroacetate ester derivative of UDCA was selected for GC analysis since it is easily and rapidly prepared by a one-step reaction. Biliary UDCA levels were determined by a rapid and simple high-performance liquid chromatographic (HPLC) method with on-line sample purification. This analytical protocol was used to investigate the pharmacokinetic of a new sustained-release capsule of UDCA in comparison with a reference immediate-release preparation after single oral administration. Statistical evaluation of the area under the plasma concentration-time curves indicated that two formulations are equivalent with regard to the amount of drug absorbed. However, pharmacokinetic data showed that with the sustained-release preparation a significantly delayed mean peak plasma level was reached compared with the reference preparation. Moreover, the immediate- and extended-release capsules were found to achieve a comparable degree of biliary enrichment with UDCA.

Adult↗
PubMed2000

Biochemical assessment and clinical evaluation of a non-ionic adsorbent resin in patients with intractable jaundice.

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 effects were observed. Our data suggest that plasmaperfusion through this resin is safe and efficient for removal of bilirubin and bile acids in jaundiced patients. Thus, it may serve as a method of artificial liver support in the treatment of cholestatic syndromes.

Aged↗
PubMed1999

Morphological and functional evaluation of isolated rat hepatocytes in three dimensional culture systems.

Various three-dimensional configurations, such as polyester tissue and woven-nonwoven, hydrophilic polyester fabric, either collagen-coated or uncoated, were investigated as potential scaffold for hepatocyte culture, in view of their use in bioreactors for hybrid liver support systems. Attachment, morphology and ultrastructure of primary adult rat hepatocytes were evaluated, as well as urea production and ammonium detoxification during a 24h incubation period in serum-free tissue culture medium. As control, hepatocytes were also plated onto collagen-coated dextran microcarriers and on plastic petri dishes, either collagen-coated or uncoated. In all the three-dimensional cultures, hepatocytes appeared morphologically intact without any statistically significant difference in metabolic activity. Collagen-coating did not influence cell attachment to polyester substrates, whereas woven-nonwoven hydrophilic polyester fabric may offer some potential advantages as three-dimensional system for hepatocyte culture in hybrid liver support systems.

Animals↗