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P Pazzi

Publications and source records attributed to P Pazzi.

At least 37 records · Page 2Linked to original sources

In vitro morphological and functional characterization of isolated porcine hepatocytes for extracorporeal liver support: bile acid uptake and conjugation.

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.

Animals↗

An update on high-yield hepatocyte isolation methods and on the potential clinical use of isolated liver cells.

Isolated hepatocytes are a suitable system for the study of hepatic physiology and metabolism. They are also used for pharmacological and toxicological studies related to hepatic uptake, metabolism, excretion and toxicity of xenobiotics, as well as morphological and metabolic effects induced in the liver as a result of drug or toxic substance exposure. In this paper, the enzymatic methods for hepatocyte isolation in some mammalian species are reviewed, and methods for evaluating cell purification and assessment of cellular morphology and function are also examined. More recently, interest in hepatocyte transplantation has increased, and the clinical experimentation of hepatocyte-based liver support systems has attracted the attention of scientists and hepatologists. From a clinical perspective, using isolated hepatocytes could be useful both for supporting an acutely devastated liver, a chronically diseased liver, and for correcting genetic disorders resulting in metabolically deficient states. Reports of clinical usage of isolated allogenic hepatocytes in hepatocellular transplantation and of xenogenic liver cells in constructing bio-artificial liver support systems are promising, and are renewing interest in the development of methods for isolation and purification of hepatocytes.

Animals↗

Short-term low-dose pantoprazole-based triple therapy for cure of Helicobacter pylori infection in duodenal ulcer patients.

BACKGROUND: The eradication of Helicobacter pylori infection has been achieved using various therapy regimens, but the efficacy of the proton-pump inhibitor pantoprazole as part of these regimens has not yet been widely tested. AIM: To evaluate the efficacy and tolerability of a 1-week low-dose pantoprazole-based triple therapy in patients with H. pylori-positive duodenal ulcer. METHODS: In an open single-centre prospective study, 71 patients with endoscopically proven active duodenal ulcer and H. pylori infection received pantoprazole 40 mg o.m. for 4 weeks, and during the first week a combination antimicrobial treatment comprising tinidazole 500 mg b.d. plus clarithromycin 250 mg b.d. H. pylori eradication was defined as concordant negative histology and rapid urease test performed at endoscopy 4-6 weeks after the end of treatment, confirmed 4 weeks later by 13C-urea breath test. RESULTS: Sixty-six patients (93%) completed the trial and five patients were lost to follow-up. H. pylori infection was cured in 61 out of the 66 patients who completed the trial (per-protocol analysis: 92.4%, 95% CI: 83.2-97.5%; intention-to-treat analysis: 85.9%, 95% CI: 75.7-93.0%). At final endoscopy, 65 out of 66 patients had healed ulcer (98.5%). Mild adverse events occurred in six patients (9.1%). CONCLUSIONS: One-week low-dose pantoprazole-based triple therapy is a simple, effective and well-tolerated regimen for ulcer healing and H. pylori eradication in patients with duodenal ulcer.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Nonsteroidal antiinflammatory drug use and gallstone disease prevalence: a case-control study.

OBJECTIVES: Conflicting results on the relationship between gallstone disease and the use of nonsteroidal antiinflammatory drugs (NSAIDs) have been reported, but studies on the effect of NSAID use in populations not selected on the basis of a high risk for gallstone development are still lacking. METHODS: We conducted a case-control study involving 216 patients, regular NSAID users (43 men and 173 women) consecutively admitted to a rheumatology department, suffering from rheumatoid arthritis (n = 147), osteoarthritis (n = 49), and ankylosing spondylitis (n = 20). Two-hundred sixteen patients who were not NSAID users, matched for gender, age, and body mass index, consecutively admitted to a medical department for various medical pathologies, acted as a control group. All patients underwent upper abdomen ultrasonography. RESULTS: The overall prevalence of gallstones was similar in the two groups: 24.0% in NSAID users (15.7% actual stones and 8.3% previous cholecystectomy) and 21.3% in controls (13.9% gallstones and 7.4% cholecystectomy). The prevalence of gallstone disease was significantly higher in women than in men, and the mean age was higher in gallstone patients than in gallstone-free patients, in both groups. No significant differences in type and duration of arthritis condition, type and dose of NSAID taken, and duration of treatment between gallstone patients and gallstone-free patients were found. On logistic regression analysis only female gender, aging, and family history of gallstone disease were significantly associated with the presence of gallstones, whereas no relationship between NSAID use and gallstone disease was found. CONCLUSIONS: Chronic NSAID ingestion does not seem to prevent gallstones in arthritis patients; in these patients gallstone disease is associated with classic risk factors (female gender and age).

Age Factors↗

[Dyspepsia: a reappraisal problem].

Dyspepsia is a major public problem. It occurs in 25-40% of the general population negatively affecting the quality of life. 2-3% of the patients visited by the GP and up to 30% of those visited by the gastroenterologist have dyspepsia. Both diagnostic procedure and therapy are expensive. Definition, aetiology and pathogenesis of the disorder are not clear cut. The aim of this review is to outline the main trends in the relevant area of the clinical practice. The authors choose the most comprehensive definition among the thirty of the medical literature. To rule out, the most commonly and frequently wrong opinions risk factors have been examined. The authors distinguished between symptoms of function and organic dyspepsia and those of Irritable Bowel Syndrome and Gastro-Esophageal Reflux Disease, which often overlap and make difficult the management of the patient. The aetiology and pathogenesis have also been discussed, with particular emphasis on Hp. Advantages and drawbacks of different diagnostic approaches have been investigated. An age and symptoms related approach of the cases with dyspepsia is proposed, which allows to manage the patient without the necessity of invasive procedures. It is finally suggested that are cases which can be managed by the GP and others for whom the gastroenterologist intervention is mandatory.

Adult↗

Bile salt-induced cytotoxicity and ursodeoxycholate cytoprotection: in-vitro study in perifused rat hepatocytes.

OBJECTIVES: Membrane toxicity induced by hydrophobic bile salts may be important in liver diseases. Administration of ursodeoxycholate reduces serum liver enzymes in chronic liver diseases, but the nature of this effect is still unclear. We aimed at establishing a convenient in-vitro system for investigating the hepatotoxic properties of hydrophobic bile salts and the putative hepatoprotective effect of ursodeoxycholate. METHODS: About 100 mg of freshly isolated rat hepatocytes were suspended on a resin column (Bio-Gel P4 fine) and perifused with different concentrations of bile salts. The effluent was collected at 5-min intervals and assayed for lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity. Enzyme leakage induced by bile salts was compared with that induced by Triton X-100 (Union Carbide, Danbury, CT, USA) at different concentrations. After perifusion, hepatocytes were collected for electron microscopic observation. RESULTS: Cytotoxicity of individual bile salts, assessed by enzyme release, was time and concentration dependent and corresponded to their hydrophilic-hydrophobic balance. Perifusion with hydrophilic bile salts, cholate and ursodeoxycholate, did not result in a significant enzyme release in concentrations up to 5 mmol/l, whereas hydrophobic bile salts, chenodeoxycholate and deoxycholate, induced significant enzyme leakage even in low concentrations, 0.5 and 0.1 mmol/l, respectively. Addition of ursodeoxycholate significantly reduced the hepatotoxic effect of deoxycholate. This protective effect was evident within minutes. The ultrastructural appearance of hepatocytes exposed to hydrophobic bile salts was very similar to the non-specific cellular lysis observed after exposition to Triton X-100, suggesting that they act mainly in a detergent-like fashion. CONCLUSION: Perifused rat hepatocytes seem a convenient in-vitro system for investigating the hepatotoxic properties of bile salts and hepatoprotective effect of ursodeoxycholate, offering the opportunity to investigate the effects of bile salts under dynamic conditions, mimicking the in-vivo situation, and allowing continuous enzyme release monitoring. Hydrophobic bile salts seem to act mainly in a detergent-like fashion; ursodeoxycholate-related hepatoprotection could be due not only to a dilution effect of toxic bile salts, but also to a direct cytoprotective effect.

Animals↗

Colon involvement in systemic sclerosis: clinical-radiological correlations.

About one third of all patients with systemic sclerosis (SS) presents colon abnormalities, although these may be underestimated because they frequently remain asymptomatic for a long time. Thirty-five patients (33 women and 2 men; mean age 56.5 years; mean disease duration 11.9 years) affected by SS (25 with limited and 10 with diffuse pattern of skin involvement) were investigated using barium enema to detect radiological changes in the colon, and to correlate them with other visceral involvement, autoantibody profile, abdominal symptoms and duration of the disease. Ten patients (28.6%) showed X-rays abnormalities (excluding isolated diverticula), wide-mouthed sacculations being the most frequent finding. Our data confirm that the colon is frequently involved in SS, even in the limited form of the disease. The most relevant finding was the dissociation between clinical symptoms and radiological features which proved to be more evident among the patients with limited SS. No correlations were found between the radiological picture and any other parameter, thus suggesting that careful evaluation of the colon should be performed in any patient suffering from the disease.

Adult↗

Quality improvement in gastrointestinal endoscopy: microbiologic surveillance of disinfection.

BACKGROUND: Cleaning and disinfection procedures play an essential role in the prevention of infection transmission in gastrointestinal endoscopy. In spite of published detailed guidelines, several variants and weak points still exist. METHODS: Cleaning-disinfection procedures were carried out according to "Working Party, Sydney 1990." A microbiologic surveillance protocol tested the contamination of endoscopes and of automatic washing machines. To assess and improve the efficacy of disinfection, we adopted a quality assurance program. RESULTS: During a 2-year follow-up, the outside surfaces of gastroscopes were contaminated in 60.5% and channels in 41.3%; the outside areas of colonoscopes were contaminated in 62.3% and channels in 40.3%. Isolated bacteria were gram-negative organisms, particularly Pseudomonas species, and gram-positive organisms, mostly Staphylococcus species. The water reservoirs of automatic washing machines were frequently contaminated by Pseudomonas aeruginosa. The disinfection of washing machines and alcohol rinsing of endoscopes after standard procedures significantly reduced the bacterial contamination. CONCLUSIONS: The microbiologic surveillance pointed out the main weak points that could be improved by the adoption of corrective interventions. Quality assurance is a feasible method to assess the efficacy of cleaning-disinfection, and its wide application would improve quality of care.

Colony Count, Microbial↗

Repeated bile acid therapy for the long-term management of cholesterol gallstones.

BACKGROUND/AIMS: Following non-surgical treatment, cholesterol gallstones recur in a high proportion of patients, and recurrence cannot be predicted nor effectively prevented. Our aim was to test prospectively the viability and the efficacy of repeated bile acid therapy, in which recurrent stones are diagnosed at an early stage by regular ultrasound monitoring and promptly retreated, as a strategy for the management of these patients in clinical practice. METHODS: One hundred and seventy-two consecutive patients were recruited upon achieving complete gallstone dissolution using non-surgical therapy (bile acids or lithotripsy plus bile acids), and followed up at 6-monthly intervals by ultrasound scan. Gallstone recurrence was promptly treated by a combination of ursodeoxycholic acid plus chenodeoxycholic acid (5 mg/kg per day each) for a period of 2 years, or less if complete redissolution was achieved. Median follow-up period was 34 months (range 6-70). RESULTS: Forty-five patients had gallstone recurrence; of these, 39 underwent one or more repeated courses of bile acid therapy (follow-up data available in 27). Gallstone recurrence rate was 15% at 1 year and 47% at 5 years. Average annual redissolution rate of recurrent gallstones (intention to treat) was 41%. The proportion of gallstone-free patients in the whole population was 88%, 84%, 77%, 78%, 75% at 1-5 years, respectively, and rose to > 90% at 3 years onwards in patients with single primary stones. CONCLUSIONS: We conclude that repeated bile acid therapy maintains the majority of patients gallstone free, and is therefore an effective long-term management strategy, especially in patients with primary single gallstones.

Adolescent↗

High effectiveness and safety of one-week antibiotic regimen in Helicobacter pylori eradication.

BACKGROUND: Helicobacter pylori is strongly associated with peptic ulcer: H. pylori eradication markedly decreases the recurrence rate of duodenal and gastric ulcer, but the optimum length of antibiotic therapy in the eradication of H. pylori is still unclear. AIM: To verify the effectiveness and side-effect profile of an eradicating regimen consisting of omeprazole 20 mg daily for 4 weeks and, during the first week, combination antimicrobial treatment with tinidazole 500 mg b.d. plus clarithromycin 250 mg b.d. in patients with active duodenal and gastric ulcer. METHODS: One hundred and ninety-six duodenal ulcer patients and 27 gastric ulcer patients with H. pylori infection were admitted into an open prospective study. Compliance was assessed by an accurate interview. RESULTS: Overall, H. pylori was successfully eradicated in 201 of 223 patients (intention-to-treat 90.1%; 95% CI = 85-94%): 176 of 196 duodenal ulcer patients became H. pylori-negative (89.8%; CI = 85-94%) as well as 25 of 27 gastric ulcer patients (92.6%; CI = 76-99%). Compliance was excellent in 221 of 223 (99.1%) patients evaluated as having taken all the medication as prescribed. Sixteen patients (7.2%) developed mild side effects during treatment. CONCLUSION: This combination treatment had excellent results with almost absolute compliance and a very low rate of minor side effects.

Adult↗

Brush cytology: a reliable method to detect Helicobacter pylori.

This study was conducted to verify the reliability of brush cytology in detecting Helicobacter pylori in an unselected group of patients with duodenal ulcer (DU) and nonulcer dyspepsia (NUD). Endoscopy was performed on 416 consecutive patients: group A, 94 with active DU; group B, 176 patients with DU after omeprazole (n = 78), ranitidine (n = 43), or triple anti-H. pylori therapy (n = 55); and group C, 146 patients with NUD. During endoscopy, the gastric mucosa was brushed and two biopsy samples from the antrum and body were obtained for histology. In 65 patients, culture of the brush-collected materials also was performed as was that from of biopsy samples. The overall frequency of H. pylori presence detected by brush cytology was significantly higher compared with that of histology (p < 0.001), particularly in group A (p < 0.05), group C (p < 0.05), and in patients with DU after omeprazole treatment (p < 0.01), but not in patients with DU after ranitidine or anti-H. pylori treatment. The overall frequency of H. pylori-positive cultures from the brush-collected material was higher compared with cultures from the biopsy samples (38.5% vs. 24.6%), particularly in the NUD group (32.6% vs. 16.3%). Brush cytology is more sensitive than histology, besides being faster and cheaper, for the assessment of H. pylori infection, particularly when the density of the bacteria is low.

Adolescent↗

Prevalence of previously undiagnosed gallstones in a population with multiple risk factors.

This study was aimed at investigating whether it is possible, on the basis of the presence of multiple factors, to select a population with a higher prevalence of gallstones than that predicted simply on the basis of age and sex. Thus, we selected and screened for the presence of previously undiagnosed gallstones subjects with at least four of the following variables: female sex, age over 40, obesity, diabetes, biliary colic, family history of gallstones or cholecystectomy, hypertriglyceridemia, parity, and oral contraceptive use. The a priori probability (or expected prevalence) of having previously undiagnosed gallstones was calculated for each subject on the basis of sex and age according to data derived from epidemiological studies performed in Italy in the general population. Among the 821 males and 3930 females participating in this study, previously undiagnosed gallstones (GS) were found in 135 (16.4%) males and 691 (17.6%) females. The ratio between observed and expected prevalence of GS was higher in males (3.09) than in females (2.32). The highest ratios between observed and expected prevalence of GS were found in the lowest classes of expected prevalence in both sexes. The best predictors of the presence of GS were age, biliary colic, and diabetes in males and age, biliary colic, obesity, and number of pregnancies in females. It is concluded that selection of subjects with multiple factors associated with GS increases the a priori probability of GS diagnosis by a factor 2 in females or 3 in males. Stricter selection criteria should be used for females.

Adult↗

Postprandial gallbladder motor function: refilling and turnover of bile in health and in cholelithiasis.

BACKGROUND & AIMS: Impaired gallbladder emptying is implicated in gallstone disease. Ultrasonography and scintigraphy have shown conflicting results because the former is influenced by postprandial refilling, whereas the latter is not influenced by refilling. The aim of this study was to measure postprandial refilling and turnover of bile by combining the two techniques. METHODS: Simultaneous scintigraphy and ultrasonography were used in 14 patients with gallstones and 11 healthy controls. Measurements were performed while the patients were fasting and at 10-minute intervals after a standard meal for 90 minutes, and the measurements were used to calculate postprandial refilling, turnover of bile (in milliliters), and turnover index. RESULTS: Ultrasonography and scintigraphy provided different gallbladder emptying patterns. Compared with controls, patients with gallstones had impaired emptying by both scintigraphy (P < 0.0001) and ultrasonography (P < 0.01). Postprandial refilling and turnover were both reduced between 60 and 90 minutes (P < 0.05), and the turnover index was markedly reduced (1.8 vs. 3.5; P < 0.001). CONCLUSIONS: Simultaneous scintigraphy and ultrasonography provide a new model of gallbladder motor function showing that refilling begins immediately postprandially. In healthy controls, the gallbladder postprandially handles up to six times its basal volume within a period of 90 minutes, but this turnover of bile is markedly reduced in cholelithiasis causing a reduced washout effect of the gallbladder contents, including cholesterol crystals.

Analysis of Variance↗

HPLC assay of conjugated bile acids in human fluids using on-line sample pretreatment on a standard isocratic chromatograph.

A rapid and simple on-line purification procedure was developed for determining the conjugated bile acids in human fluids by high-performance liquid chromatography (HPLC). Biological samples were diluted and directly injected without further treatment onto a pre-column dry-packed with 40-microns octadecylsilica and installed at the injector loop position. After washing the pre-column with 40% methanol in acetate buffer and then with water, the retained compounds were back-flushed by the mobile phase onto the analytical column during the normal course of chromatography. The method was found to be accurate and reproducible. The levels of conjugated bile acids in serum, duodenal bile and gastric juice from patients with hepatobiliary and gastric diseases were determined by on-line pre-column clean-up and reversed-phase HPLC.

Bile↗

Misoprostol for the treatment of chronic erosive gastritis: a double-blind placebo-controlled trial.

OBJECTIVE: To assess the efficacy of misoprostol for the treatment of chronic erosive gastritis and associated symptoms. METHODS: 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. RESULTS: 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 Helicobacter pylori was rather low (30%), and no effect of treatment was observed. CONCLUSIONS: Patients with symptomatic chronic erosive gastritis seem to profit from treatment with misoprostol: the treatment with misoprostol, but not with placebo, was effective in significantly reducing the extent of symptoms. Such an improvement was associated with a substantial improvement in the endoscopic and histologic appearance of the gastric mucosa.

Chronic Disease↗