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A 24-week, double-blind, randomized study at 13 centres compared the efficacy and safety of 20 mg famotidine nocte and 150 mg ranitidine h.s. for the prevention of duodenal ulcer recurrence. All participants had been successfully treated for an acute duodenal ulcer with 40 mg famotidine nocte. Patients were endoscoped at baseline and at 24 weeks, unless symptoms warranted earlier examination: of the 208 patients enrolled, 86 who received famotidine and 84 who received ranitidine met all protocol criteria and were considered evaluable. Intention to treat and per protocol analyses showed non-significant trends in favour of famotidine (P = 0.44 and 0.16, respectively). During the 24-week observation period, 16.3% of the famotidine group and 25% of the ranitidine group had an ulcer recurrence (95% CI of percentage difference -0.22 + 0.04). At 24 weeks, relief of day and night pain was reported by 81.2% and 91.8% of the famotidine-treated patients, respectively. The corresponding figures in the ranitidine group were 73.5% and 85.5%. No laboratory abnormalities related to the study-drugs were noted and only two drug related (possibly or probably) adverse experiences were reported, both in the famotidine group. The data from this study therefore, supports the conclusion that the efficacy of 20 mg famotidine nocte is comparable to that of ranitidine in preventing duodenal ulcer recurrence, with comparable tolerability for long-term therapy.

Canova D, De Bona M, Rumiati R, Masier A, Ermani M, Naccarato R, Cozzi E, Ancona E, Burra P. Understanding of and attitude to xenotransplantation among Italian university students: impact of a 3-yr university course. Xenotransplantation 2006; 13: 264–271. © Blackwell Munksgaard, 2006 Abstract: Background: Young people, and students in particular, generally have a positive attitude to xenotransplantation. We reported previously that university students attending their first year approved of the idea of transplanting animal organs into humans. The aim of this study was to evaluate the impact of a 3-yr course at various faculties on the university students’ understanding of and attitude to xenotransplantation. Methods: University students in their fourth year at five different faculties of Padua University (Italy), who had previously been surveyed in exactly the same way 3 yr earlier, were re-administered an anonymous 19-item questionnaire on their attitude to xenotransplantation. Results: A total of 453 students completed the fourth year questionnaire (84 males, 369 females; mean age 24.6 yr, range 21–36 yr). Students were attending courses in Medicine (22.1%), Veterinary Science (16.5%), Agriculture (10.4%), Educational Sciences (22.1%) and Psychology (28.9%). In their fourth year, 85% of the students knew that animal organs could, at some stage, be transplanted into humans, 81.5% approved of this idea and 84% would accept an animal organ to save their life if necessary (these percentages were 88%, 78% and 76%, respectively 3 yr earlier). A significantly larger proportion of the students who approved of xenotransplantation were attending science courses rather than art courses, while no differences emerged as regards gender. Those who refused xenotransplantation justified their position mainly on ethical-moral (41.7%) and immunological (35.7%) grounds. Conclusion: As in their first year, so too in their fourth, University students were well informed about the feasibility of transplanting animal organs into human beings and those attending science courses were more likely to accept this idea than art students. Approval of xenotransplantation was much the same among fourth year males and females, whereas in the first year, male students had approved more than female students.

The aim of this study was to describe the clinical characteristics of hepatitis C virus (HCV)-infected patients with primary biliary cirrhosis (PBC) by comparison to patients with both antimitochondrial (AMA) positive and AMA negative PBC.All patients consecutively diagnosed as having PBC between 1973 and 1999 who had a regular follow-up of at least 2 yr were prospectively included in the study. The mean follow-up was 8.3 +/- 5.7 yr. Survival was calculated according to Kaplan-Meier curves.A total of 170 patients with PBC were considered. The syndrome with PBC and HCV infection (HCV-infected PBC patients) was recorded in 14 patients (13 women and one man), whereas 135 patients had AMA positive PBC and 18 had AMA negative PBC. Only three patients fulfilled the criteria for overlap syndrome involving PBC and autoimmune hepatitis. At presentation, the HCV-infected PBC group had significantly lower levels of ALP, gamma-glutamyl transpeptidase, and IgM than the AMA positive or AMA negative PBC patients (p0.01). With regard to the autoantibody profile, there was a significant association with LKM and HCV-infected PBC patients (21.4%), whereas ANA was significantly higher in AMA negative PBC patients than in the other two groups (83% vs 21.4% in the HCV-infected PBC patients and 38.5% in the AMA positive PBC group). No differences were found regarding the association with autoimmune conditions. During follow-up, hepatocellular carcinoma (HCC) developed more frequently in the PBC/HCV overlap group (i.e., three of 14 vs four of 135 patients with AMA positive PBC, p0.05). Survival curves were similar in HCV-infected PBC patients and AMA positive PBC, whereas the AMA negative group had a significantly slower decline (relative risk (RR) = 2.44, p0.05).HCV-infected PBC patients are characterized by a biochemical profile with a modest rise in cholestatic enzymes but a high risk of developing HCC during follow-up.

Alpha1-antitrypsin ( α 1-AT) deficiency is the most common genetic cause of liver disease in infants and children. The major clinical manifestations include liver disease (primarily in children) and emphysema in adults. For patients who progress to cirrhosis and liver failure, liver transplantation provides a metabolic cure for the deficiency and presumably prevents the associated complications. Several case reports in the pediatric literature describe glomerulonephritis in the setting of severe α 1-AT deficiency, but this association is less well documented in adults. End-stage chronic kidney disease is a rare finding in the literature and kidney transplantation is the treatment of choice. We report on a 15-year-old boy with α 1-AT deficiency and consequent end-stage liver disease and membranoproliferative glomerulonephritis rapidly progressing to renal failure, who successfully underwent combined liver-kidney transplantation.

In alcohol-related liver disease, free radicals play a part in the pathogenesis of liver damage and may influence cell turnover. The aims of this study were to correlate lipid peroxidation, antioxidant defence and iron metabolism with cell proliferation and apoptosis in alcoholic liver injury, and also in comparison with virus-related liver disease. In 45 patients [10 with chronic alcoholic liver damage (CALD), 24 with HCV-related (HCV) and 11 with HBV-related chronic hepatitis (HBV)], and 10 control subjects, we investigated serum ferritin, liver tissue iron, cysteine, reduced/oxidized glutathione, malondialdehyde, histology with hepatocyte proliferation and the apoptotic index. Ferritin, iron levels and malondialdehyde were significantly higher in HCV and CALD than in HBV, and malondialdehyde correlated with both iron and ferritin. Glutathione levels were significantly lower in CALD than in HCV, HBV and control subjects, whereas cysteine levels were significantly higher. The apoptotic index was slightly lower in CALD, with apoptosis occurring more frequently in the centrilobular area, while CALD had fewer proliferating hepatocytes, both overall and in the periportal and centrilobular areas. This study confirms that chronic alcohol intake: (1) induces more peroxidative damage, which correlates with iron loading; (2) reduces antioxidant defence, lowering reduced glutathione liver availability; (3) induces an accumulation of cysteine, a glutathione precursor/metabolite in the liver, probably due to gamma-glutamyltransferase induction; (4) correlates with a lesser extent and different distribution of hepatocyte proliferation and apoptosis than in viral liver damage. This last finding may explain the different types of liver cirrhosis deriving from alcoholic liver damage and the lower cancer risk.

Background. Heart transplant (HTx) recipients risk acquiring hepatotropic viral infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV), and the impact of these infections on post-HTx survival remains unclear. The aim of the present study was to define the prevalence, clinical features, and natural history of HBV and HCV infections in a cohort of HTx recipients. Methods. We retrospectively studied 360 consecutive patients who had undergone HTx. Clinical picture, hepatic injury indexes, and HBV/HCV viral serology were followed post-transplant. Results. During follow-up (average, 8 ± 3.1 years), 49 (16.5%) of the HTx recipients tested positive for at least 1 of the 2 viruses (3.1% HBV, 12% HCV, 0.5% concomitant infection). The prevalence of HCV infection in heart transplant recipients transplanted before and after 1990 was 28% and 4.2%, respectively, the latter being markedly lower (p < 0.001) than in earlier series of HTx recipients and much lower than expected in the age- and sex-matched general population. All HBV-positive and 58% of HCV-positive recipients developed chronic liver disease. Sixteen percent of patients developed cirrhosis during follow-up, and 8% died of end-stage liver disease. Conclusions. The prevalence of HBV and HCV in a large population of HTx recipients is not very different from that reported in the general population. Active viral replication of HBV and an aggressive natural history of both infections are seen in HTx recipients, however. The low prevalence of HBV- and HCV-related infection in recent series probably reflects current viral screening and vaccination policies.

Background and purpose : A large number of studies have contributed to the hypothesis that carotenoids, vitamins A and E are protective against atherosclerosis by acting as antioxidants. The aim of this study was to assess the relationship between plasma levels of carotenoids (α- and β- carotene, lutein, lycopene, zeaxanthin, β-cryptoxanthin), vitamins A and E, and atherosclerosis in the carotid and femoral arteries. Methods : This prospective and cross sectional study involved a randomly selected population sample of 392 men and women aged 45–65 years. Carotid and femoral artery atherosclerosis was assessed by high-resolution duplex ultrasound. Results : α- and β- carotene plasma levels were inversely associated with the prevalence of atherosclerosis in the carotid and femoral arteries ( P =0.004) and with the 5-year incidence of atherosclerotic lesions in the carotid arteries ( P =0.04). These findings were obtained after adjustment for other cardiovascular risk factors (sex, age, LDL (low density lipoproteins), ferritin, systolic blood pressure, smoking, categories of alcohol consumption, social status, C-reactive protein). Atherosclerosis risk gradually decreased with increasing plasma α- and β-carotene concentrations ( P =0.004). No associations were found between vitamin A and E plasma levels and atherosclerosis. Conclusions : This study provides further epidemiological evidence of a protective role of high α- and β- carotene in early atherogenesis.

Background/Aim: The impact of liver disease and medical complications on quality of life (QOL) and psychological distress before and after orthotopic liver transplantation (OLT) is a matter of growing interest. Methods: Perceived QOL (LEIPAD Quality of Life test) and psychological distress (Brief Symptom Inventory, BSI) were assessed in 40 cirrhotic patients listed for OLT (Group A) and in 101 liver transplant recipients (Groups B to G=0–6, 7–12, 13–24, 25–36, 37–48, 49–60 months post-OLT). Patients were also evaluated for medical complications, blood levels of immunosuppressive agents and recurrence of liver disease. Results: QOL and psychological distress were significantly better in most of the post-OLT groups than in cirrhotic patients. Among post-OLT patients, a significantly worse QOL was perceived at 13–24 months (Life Satisfaction: Group D vs G, p =0.024; Cognitive Functioning: Group D vs F, p =0.024), while significantly greater psychological distress was detected at 7–12 months (Anxiety and Interpersonal Sensitivity: Group C vs Group B, p =0.032 and p =0.023, respectively). Medical complications and immunosuppressive therapy did not influence QOL or psychological distress after OLT. Within 6 months after OLT, patients with HCV recurrence showed significantly greater Depression ( p =0.023), Anxiety ( p =0.038), Phobic Anxiety ( p =0.001), and Paranoid Ideation ( p =0.033) than anti-HCV negative patients. Conclusions: Liver transplantation improves psychological distress and most, but not all, QOL domains. Recurrent HCV infection is associated with greater psychological distress.

Bakcground: A predictable consequence of cholestasis is malabsorption of fat-soluble factors, (vitamins A, D, E, K) and other free radical scavengers, such as carotenoids. It has been suggested that oxygen-derived free radicals may be involved in the pathogenesis of chronic liver damage. Aims: (i) To evaluate retinol, α-tocopherol and carotenoid plasma levels in two groups of patients with chronic cholestatic liver disease (primary biliary cirrhosis and primary sclerosing cholangitis); (ii) to compare the respective plasma levels with those of the general population; (iii) to correlate the plasma levels with disease severity. Methods: A total of 105 patients with chronic cholestasis were included in the study: 86 with primary biliary cirrhosis (81 female, five male, mean age 55.5 ± 11 years), 19 with primary sclerosing cholangitis (seven female, 12 male, mean age 35 ± 11 years; six patients had associated inflammatory bowel disease); 105 sex- and age-matched subjects from the general population in the same geographical area (88 female, 17 male, mean age 51.3.5 ± 10 years) served as controls. Carotenoids (lutein zeaxanthin, lycopene, β-carotene, α-carotene, β-cryptoxanthin), retinol and α-tocopherol were assayed by high-pressure liquid chromatography. A food frequency questionnaire was administered to each subject to evaluate the quality and the quantity of dietary compounds. Data were processed by analysis of variance and linear regression analysis, as appropriate. Results: Both primary biliary cirrhosis and primary sclerosing cholangitis patients had significantly lower levels of retinol, α-tocopherol, total carotenoids, lutein, zeaxanthin, lycopene, α- and β-carotene than controls (P

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with clinical signs typical of "intestinal" food allergies or intolerance. The aim of this study was to characterize the clinical features of IBS patients suspected of suffering from adverse reactions to food.The study involved 128 consecutive IBS patients divided into four groups according to their main symptom on presentation at our outpatient clinic. A detailed medical history was recorded, paying particular attention to any allergies and reported intolerance to food. Each patient was screened for allergies; intestinal permeability tests was performed in randomly selected patients from different groups. Findings were analyzed using the chi2 test.Adverse reactions to one or more foods were reported by 80 patients (62.5%); skin prick tests (SPT) were positive in 67 patients (52.3%) with no significant differences between patients complaining of different symptoms. Patients who reported a food intolerance had more positive SPTs than those who did not (47 of 80 [58.7%] vs 20 of 48 [41.7%]); this difference was not statistically significant, although it suggests a trend (p0.0610). There was little consistency between the specific foods reported to cause intolerance and those resulting from the tests (11 of 80 patients, 13.7%). The intestinal permeability test was normal in 29 of 33 patients (87.9%).More than 50% of IBS patients were found sensitized to some food or inhalant without any typical clinical signs. Patients were unable to identify potentially offending foods. The lack of a correlation between SPT results and reported food allergies needs further investigation to clarify the pathophysiology and improve the diagnosis of intestinal food allergies.

Aim: To evaluate the efficacy of otilonium bromide, a spasmolytic agent, in the treatment of irritable bowel syndrome using modern and validated diagnostic criteria. Methods: Three hundred and seventy-eight patients with irritable bowel syndrome were enrolled in the study. At entry, endoscopy/barium enema, clinical examination and laboratory tests were used to rule out organic diseases. After a 2-week placebo run-in, 325 patients were randomly assigned to receive either otilonium bromide 40 mg t.d.s. or placebo for 15 weeks. Abdominal pain, abdominal distension and disturbed defecation were scored at the beginning of the study and every 5 weeks. A global determination of well-being by visual analogue scale and the tenderness of the sigmoid colon were also scored. Results: The reduction in the number of abdominal pain episodes was significantly higher (P

Osteodystrophy is a major complication in primary biliary cirrhosis (PBC) and a significant problem for patients who require a liver transplant. Treatment for osteodystrophy has yet to be standardized. The goal of this pilot study was to assess the efficacy and tolerability of alendronate sodium, a potent specific inhibitor of osteoclast-mediated bone resorption. The study comprised 15 post-menopausal PBC patients (mean age, 64.25 ± 8.77 years) with severe osteodystrophy. Four patients had histologic stage II disease, 8 stage III, and 3 stage IV. All patients had a T score below 2, indicating a fracture risk of 60%. All patients received two courses of alendronate sodium (10 mg/d for 3 months, separated by a 2-month interval). The following variables were assessed at baseline and after 10 months: bone mineral density (BMD) (by dual-energy x-ray absorptiometry in the lumbar spine), calcium, sodium, potassium, creatinine, 25-hydroxyvitamin D, parathyroid hormone, and osteocalcin. No patients dropped out of the study, and therapy was well tolerated by all patients. At the end of treatment, BMD increased significantly compared with baseline (0.714 ± 0.115 g/cm 2 vs 0.740 ± 0.108 g/cm 2 ). Although not statistically significant, a trend toward an increase in serum osteocalcin levels (1.4 ± 1.5 ng/mL vs 2.6 ± 1.4 ng/mL) was evident. These preliminary findings suggest that alendronate sodium may be helpful in treating severe osteodystrophy in postmenopausal patients with PBC. Larger, controlled trials using long-term treatment with alendronate sodium are needed to establish the efficacy and safety of this drug.

Bone mineral density (BMD) and mineral metabolism were assessed in 54 patients with end-stage liver disease who were evaluated for orthotopic liver transplantation (OLT) and assessed 3, 6, and 12 months after surgery in 26 patients who underwent OLT. Serum and urinary electrolyte and mineral levels, serum liver function test results, and parathyroid hormone (PTH), osteocalcin (BGP), 25-hydroxyvitamin D, and urinary hydroxyproline levels were assessed. BMD of the lumbar spine was measured at baseline and 3, 6, and 12 months after OLT. At baseline, 40.7% of patients had BMD below the fracture threshold (0.800 g/cm2). Using multiple stepwise regression analysis, we found that BMD was significantly (P < .0001) affected by age, serum creatinine level, and PTH level but not by indices of cholestasis or liver function. In the patients who underwent OLT, a 1.4% reduction (P < .006) was observed in BMD 3 months after OLT. Thereafter, BMD returned to pretransplant values. A significant increase in serum BGP was observed after 6 (P < .02) and 12 (P < .005) months. PTH levels increased progressively 3 (P < .02), 6 (P < .001), and 12 (P < .0001) months after OLT. This increase did not seem to be caused by cyclosporine-induced nephropathy. It was concluded that osteopenia is a major complication in hepatic cirrhosis, regardless of its causes. The increase in serum BGP levels 6 and 12 months after OLT indicates metabolic activation of osteoblasts. The increase in PTH levels after OLT warrants further investigation.

The present study evaluated the quality of life (QOL) of adult cirrhotic patients before orthotopic liver transplantation (OLT), the effect of OLT on QOL in the long-term and the effect of HCV recurrence within medical complications on QOL. Three groups of patients were studied: 19 pre-OLT, 33 during the first year post-OLT and 41 1 to 5 years post-OLT. The patients completed questionnaires on QOL and underwent liver function tests, immunosuppressive drug blood level determinations and medical complications evaluation. Somatization and depression and anxiety scores improved significantly during the first year post-OLT compared with pre-OLT, but they worsened again during the 1-5-year period post-OLT. Physical functioning and life satisfaction scores improved significantly during the first year post-OLT completed with pre-OLT and the improvement persisted 1-5-year during the period post-OLT. Patients with HCV recurrence compared with patients without HCV recurrence during the first year post-OLT showed a significant worsening of most of the domains of QOL. In conclusion, OLT improved most of the domains of QOL by the end of the first post-transplant year, though the improvements did not all persist in the long-term. Recurrence of HCV infection plays a major role in the impairment of QOL after OLT.

Objective: Impaired quality of life (QOL) in patients with ulcerative colitis (UC) may be a prominent feature of the disease, and in some cases, may become an indication for surgical treatment. The objective of this study was to assess QOL in patients who underwent proctocolectomy with ileo-anal anastomosis with a J pouch for severe UC and to compare it with patients with UC of different severity who were under medical treatment. Methods: We used a validated, disease-specific research instrument (a 29 item, self-administered questionnaire) that examines the following four functions: intestinal (score 0–24) and systemic symptoms (0–21), and emotional (0–27) and Social Function (0–15). High scores indicate an impairment of the function examined and the sum of the four scores (maximal total score = 87) reflects the patient's QOL. We studied 29 operated patients (22 men, mean age 35 yr, mean time after intervention 3.8 yr) and compared their scores with those of 57 UC patients (39 men, mean age 36 yr) with different degrees of disease activity, and with those of 72 healthy controls (38 men, mean age 31 yr). Results: In UC, scores were significantly higher than in controls, increasing with the severity of the disease. Even patients in remission had higher scores than controls in the “systemic” (4.6 vs. 2.0) and emotional (5.6 vs. 2.5) functions. Patients who underwent surgical treatment had much better scores than patients with severe disease (total score 20.1 vs. 38.2), with values comparable to those of patients in remission or with mild disease activity. There was no significant gender difference, either for UC and ileo-anal anastomosis patients, or in healthy controls. Conclusion: In patients with UC, even in remission, there is a measurable impairment of QOL, which increases with the severity of disease. Operated patients have a QOL that is comparable to that of patients in remission or with mild disease, and proctocolectomy with ileo-anal anastomosis may restore an acceptable QOL in patients with moderate/severe UC.

BACKGROUND & AIMS: Hepatobiliary complications occur in inflammatory bowel disease and may be caused by the translocation of intestinal toxins from portal blood into bile through leaky hepatocyte tight junctions. The role of tight junctions in the pathogenesis of hepatobiliary complications in experimental inflammatory bowel disease was investigated. METHODS: Colitis was induced in rats by intracolonic instillation of trinitrobenzene sulfonic acid. The function of hepatocellular tight junctions was evaluated in perfused livers by measuring early (paracellular) horseradish peroxidase excretion into the bile and by electron microscopy and semiquantitative analysis of lanthanum penetration through the tight junction and into bile canaliculi. Immunofluorescent localization of cingulin and ZO-1 was used to study the structure of hepatocyte junctions. RESULTS: Colitis was associated with increased serum bilirubin and bile acid concentrations, a 2.5-fold increase in paracellular biliary excretion of horseradish peroxidase, and a ninefold increase in lanthanum permeability. Liver histology and cingulin and ZO-1 localizations were similar to normal liver. CONCLUSIONS: Experimental colitis is associated with hepatobiliary complications and an increased hepatocyte tight junctional permeability to horseradish peroxidase and lanthanum. Subtle alterations in tight junction function may be involved in the pathogenesis of hepatobiliary injuries in inflammatory bowel disease. (Gastroenterology 1997 Oct;113(4):1347-54)

The immunosuppressive agent cyclosporin A (CsA)is known to cause cholestasis. Transcellular andparacellular transport of macromolecules contribute,albeit to a minor extent, to bile formation, but little is known about the effects of CsA on thesepathways. The aims of this study were to investigate theinfluence of CsA on tight junction (paracellular)permeability and on transcytotic vesicular pathways labeled with horseradish peroxidase (HRP) inperfused rat liver. Livers from male Sprague-Dawley ratswere perfused with Krebs-Henseleit buffer (albumin 1%,RBC 20%, and amino acid mixture). Taurodehydrocholate (1 μM/min) was coinfused into the portalvein; 1 μg/ml of CsA, dissolved in Cremophor-EL (CsAlivers), or the vehicle alone (CEL livers), was added tothe medium. Tight junction permeability was assessed by administering HRP (25 mg) as a short pulseto perfused rat livers, operating under single-passconditions. Under such conditions, HRP output into thebile shows two components: an initial peak atapproximately 3-5 min, corresponding to paracellular transferacross tight junctions, and a second peak atapproximately 15 min, corresponding to vesiculartransport. Furthermore, we assessed the vesiculartransport pathway by examining HRPlabeled vesicles in theperisinusoidal (PS) and pericanalicular (PC) areas usingultrastructural morphometric analysis. To analyze HRP inhepatocytes and to study rapid and late transcytotic vesicular pathways, a 1-min pulseof a high dose of HRP (500 and 200 mg, respectively) wasgiven. Two and 18 min after single-pass perfusion thelivers were fixed with 2.5% glutaraldehyde- 0.8% paraformaldehyde in 0.1 mM cacodylatebuffer, pH 7.8. The total pericanalicular area, theHRP-containing structures, were quantifiedmorphometrically in liver samples. At concentrations of1.2 μg/ml, CsA produced a twofold increase in theparacellular transfer of HRP to bile. The areas underthe second peak (transcellular vesicular pathway) of thebiliary HRP secretion curve were similar in CEL- and CsA-treated livers. Morphometric analysisconfirmed that CsA treatment did not affect thepercentage area of HRP-labeled vesicles in either thepericanalicular or in the perisinusoidal area at 2 min(rapid pathway) and 18 min (late pathway). Theseresults indicate that CsA increases tight junctionalpermeability whereas it does not inhibit rapid or latetranscytotic vesicle pathways.

The urokinase-type plasminogen activator (UPA) and its inhibitor PAI-1 are thought to play an important part in gastric cancer (GC) invasion and metastasis. Little is known about the behavior and prognostic impact of the receptor for UPA (UPAR). The aims of the present study were: (1) to measure UPAR, UPA and PAI-1 levels in GC and in non-malignant tissue distant from the tumor (NORM); (2) to evaluate their relationship with histomorphological parameters; and (3) to determine their prognostic value. UPAR, UPA and PAI-1 levels were determined by ELISA in GC and NORM samples from 20 patients with GC undergoing surgery. The GC was also examined in terms of the presence (n=10) or absence (n=10) of metastasis, differentiation (five differentiated, 15 undifferentiated) and histotype. Survival was analysed using life table analysis. UPAR, UPA and PAI-1 were significantly higher in GC vs NORM, in the presence of metastasis (UPAR, UPA) and in undifferentiated GC (UPAR, PAI-1). UPAR significantly correlated with UPA and PAI-1. Low levels of UPAR (P=0.04), UPA (P=0.007) and PAI-1 (P=0.02) were associated with a better survival. Our results demonstrate a sharp increase in UPAR in GC and suggest a prognostic role for it. The concomitant activation of UPAR, UPA and PAI-1 in GC confirm the important role of the plasminogen activator system in the process of invasion and metastasis.

The role of neurotensin as a physiologic regulator of exocrine pancreatic secretion is known, but the hormone has only recently been recognized as important mitogen in vitro for human cancer cells. The aim of this study was to evaluate the variations of serum levels of neurotensin in pancreatic cancer. We studied 58 patients: 13 control subjects, 20 pancreatic cancer patients, 11 chronic pancreatitis patients, and 14 cases of extrapancreatic disease. No differences were found between serum values of neurotensin in pancreatic cancer and control subjects or extrapancreatic disease. Significantly higher values were detected in chronic pancreatitis than in pancreatic cancer patients ( P

Hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related liver damage is linked to an increased risk of hepatocellular carcinoma, but the mechanisms underlying hepatitis C viral activity are not known. We therefore compared hepatocellular proliferative activity in chronic C virus-related hepatitis and in liver damage of other etiology. Hepatocyte proliferation rate was investigated in 56 patients with chronic hepatitis using the Ki67 MIB1 monoclonal antibody in archival material. According to etiology, the patients were subgrouped as follows: HCV (34), HBV (11), Alcohol (4), HCV + Alcohol (4), and Hemochromatosis (3). Proliferation rate was correlated with age, sex, etiology, disease activity, liver iron storage, free-radical production, and glutathione levels by regression and discriminant analysis. HCV-positive patients had significantly more MIB1-positive hepatocytes in the periportal area (P < .011) and in the low-proliferating perivenular area (zones 2 and 3) (P < .05). The number of MIB1-positive cells correlated directly with alanine transaminase (ALT) levels, Knodell index (KI), and, inversely, with iron saturation. By stepwise discriminant analysis, ALT levels and etiology were identified as single independent variables. These data suggest that HCV infection induces increased and abnormal hepatocyte proliferation, which might be related to the increased risk of hepatocellular carcinoma in patients with HCV-related liver damage.

Background. Cysteine proteases (cathepsin B [CATB] and cathepsin L [CATL]), the serine protease urokinasetype plasminogen activator (UPA), and plasminogen activator inhibitor type-1 (PAI-1) are thought to play an important part in cancer invasion and metastasis. The aims of this study were to measure CATB, CATL, UPA, and PAI-1 in gastric cancer (GC) and normal mucosa distant from the tumor (NORM); to evaluate whether tissue levels are related to tumor stage, grade, or histotype; to assess their prognostic relevance; and to examine UPA and PAI-1 expression immunohistochemically. Methods. Gastric cancer and NORM samples were obtained from 25 patients with gastric cancer patients undergoing surgery (17 males, 8 females; mean age, 62 years; range, 31–84 years). Antigen concentrations were measured using the enzyme-linked immunosorbent assay method. Immunohistochemistry was performed using monoclonal UPA and PAI-1 antibodies. Results. Significantly higher antigen levels were found: (1) in GC vs. NORM (CATB, CATL, UPA, PAI-1) tissues; (2) in GC with versus without metastasis (CATB, CATL, UPA); (3) in poorly or moderately versus well differentiated GC; and (4) in diffuse versus intestinal-type GC (CATB, CATL). Urokinase-type plasminogen activator, PAI-1 and CATB levels had a significant prognostic impact. Cancer and stromal cells, showed immunoreactivity to anti-UPA and anti-PAI-1 antibodies. Conclusions. These results confirm the important role of CATB, CATL, UPA and PAI-1 in gastric cancer progression. Higher levels are detected in GC with metastases, poorer differentiation, and diffuse histotype, thus identifying patients with a worse prognosis Cancer 1995; 76:367–75.

The purpose of this study was to evaluate the relationship between peripheral blood monocyte and lymphocyte subsets and response to recombinant-α2b-interferon (r-α2b-IFN) in patients with viral chronic active hepatitis (CAH). Peripheral blood mononuclear cell subsets were studied by use of flow cytometry before beginning treatment, after 24 hours, and after 15, 30, and 90 days of treatment with r-α2b-IFN (3 million U thrice weekly) in 16 patients with CAH—11 who tested anti-HCV—positive and five HBsAg-positive/anti-HBe—positive/HBV-DNA—positive (HCV = hepatitis C virus; HBsAg=hepatitis B surface antigen; HBe=hepatitis B e antigen; HBV=hepatitis B virus). r-α2b-IFN acutely decreased the number of peripheral blood B lymphocytes, natural killer (NK) cells, and T-naive cells. It also activated monocytes and T lymphocytes, as indicated by increased expression of surface human leukocyte antigen (HLA)-DR molecules and interleukin-2 receptors, respectively. These effects were no longer evident after 15 days of treatment. The number of NK cells was significantly lower in anti-HCV—positive than in HBsAg-positive patients (CD16+ cells: 277 ± 55/μL vs 450 ± 33/μL, P

Little is known about the pathogenesis of liver damage related to hepatitis C virus. The presence of steatosis or increased ferritin levels, and preliminary data on the relevance of iron as a prognostic factor prompted us to ascertain whether hepatitis C virus-related liver damage might be mediated by iron accumulation.We evaluated the degree of hepatic inflammation and steatosis, serum ferritin, transferrin saturation and iron levels, tissue iron concentrations and iron index, liver glutathione and malondialdehyde in 33 males and 20 females with chronic hepatitis C virus- or hepatitis B virus-related hepatitis (42 + 11). We also considered six patients with both alcohol abuse and hepatitis C virus, four males with chronic alcoholic liver disease and four males with genetic hemochromatosis, giving a total of 67. All diagnoses were histologically confirmed. Patients with cirrhosis were excluded.Our data show that: 1. Steatosis is more frequent in hepatitis C virus and hepatitis C virus+alcohol abuse patients; 2. In males, serum ferritin and tissue iron are significantly higher in hepatitis C virus- than in hepatitis B virus-positive patients (p0.01 and 0.05); transferrin saturation is higher (p0.05) in hepatitis C virus-positive than in hepatitis B virus-positive patients only when males and females are considered together; 3. Serum ferritin and transferrin saturation only correlate with liver iron (r = 0.833 and r = 0.695, respectively, p = 0.00001); tissue iron is significantly higher in hepatitis C virus- than in hepatitis B virus-positive patients (p0.05); 4. In patients with chronic hepatitis, serum ferritin is a better marker of liver iron storage than transferrin saturation, both in males and in females; 5. Hepatitis C virus-positive patients have higher malondialdehyde levels and activation of turnover of glutathione, probably in response to free-radical-mediated liver damage. Females have lower liver iron levels but similar trends.These findings suggest that hepatitis C virus-related liver damage is characterized by increased iron storage (possibly induced by the virus) which elicits a free-radical-mediated peroxidation, with consequent steatosis and activation of glutathione turnover.

In an attempt to elucidate further the mechanisms involved in alcohol-mediated liver damage and the correlation between alcohol and viruses in chronic liver lesions, we determined the levels of liver glutathione (GSH), thiobarbituric acid reactive substances (TBARS), iron (Fe), and zinc (Zn) in 31 patients with chronic viral hepatitis (CAH), 6 with alcohol-related chronic hepatitis (CALD), 6 with alcoholic cirrhosis (AC), 8 with primary biliary cirrhosis (PBC), and 10 healthy controls (C). Liver GSH was significantly lower in CALD and AC patients (p < 0.005). TBARS levels were significantly higher in CAH, CALD, and PBC patients (p < 0.001, < 0.02, and < 0.001, respectively). In CAH patients, alcohol consumption correlated inversely with GSH and directly with TBARS (p < 0.05). Patients with both CAH and alcohol abuse had a further reduction in liver GSH levels (p < 0.005). Tissue levels of Fe were significantly increased in CALD and AC patients with respect to controls and CAH patients, whereas no significant difference was observed in Zn. These data confirm that patients with chronic ethanol exposure reveal a depletion in liver GSH content clearly correlated with an increase in lipid peroxidation and Fe liver storage. On the other hand, these findings appear to suggest no significant change in Zn levels in chronic hepatitis.

Objective. To assess the prevalence of metabolic bone disease associated with Crohn's disease and its possible aetiopathogenic factors. Patients. The study included 20 men with long-standing, inactive Crohn's disease of the ileum or ileo-caecum (nine not resected, 11 with surgical resections) and 12 healthy age-matched controls. Interventions. Bone density (BMD) was measured using dual X-ray absorptiometry of the lumbar spine. Calciotropic hormones, vitamin D metabolites, minerals and markers of bone turnover were determined in serum, and hydroxypro line, cyclic AMP and calcium in urine. The intestinal fractional absorption of orally administered 47calcium was also assessed. Results. Of the patients, 30% had densitometric signs of bone demineralization (Z-score less than −2). Patients who had not undergone surgical resection had a lower lumbar spine BMD compared with controls (P Conclusions. Bone demineralization is frequent in Crohn's disease. Since there is no evidence of calcium malabsorption, vitamin D deficiency or active bone disease, demineralization appears to be mainly due to steroid therapy, but inflammation may have an important contributory role

The aims of this study were to investigate the rate of hepatocellular proliferation in PBC and its correlation with the site of inflammation and serum TNFα levels. Hepatic proliferation was evaluated in liver sections from 11 patients with PBC (two histological stage II, eight stage III, one stage IV) using the indirect immunoperoxidase technique with a monoclonal antibody against proliferating cell nuclear antigen (PCNA). Counter-staining with hematoxylin was performed and at least 500 nuclei were counted by two observers who blindly calculated the site of positive cells (perivenular, periportal/periseptal). The percentage of hepatocytes expressing PCNA was significantly higher in the periportal/periseptal regions than in the perivenular area (70 ± 5.8% vs. 36 ± 6.9%, P < 0.002). Hepatocellular PCNA expression in the periportal/periseptal (portal area) correlated with TNFα serum levels (r = 0.8, P < 0.03). In conclusion, hepatocellular proliferation in PBC significantly correlates with the site of inflammation and serum levels of TNFα. This data seems to confirm that inflammation and cytokines may stimulate hepatocyte DNA synthesis.

Little is known about ulcer outcome in the elderly. The aims of the present paper were to establish whether risk factors of slow-healing peptic ulcer can be demonstrated in the elderly and whether clinical differences exist between ulcer patients whose age of onset of the disease was before or after 65 years old. The short-term, open study, involving 1052 elderly patients (over 65 years) in 37 gastroenterology centers throughout Italy aimed to compare two schedules of ranitidine treatment: 150 mg twice daily versus 300 mg at bedtime. As nonsignificant differences were found between these two schedules, the sample was considered as a whole. It included 319 gastric ulcer (GU) patients, 699 duodenal ulcer (DU) patients, and 34 concomitant GU and DU cases. Ninety-three patients dropped out of the trial; 79/294 GU, 138/635 DU, and 10/30 GU+DU were found still unhealed after four weeks and 20 GU, 15 DU, and 1 GU+DU remained so after eight weeks. Statistical analysis was performed using likelihood-ratio and Pearson's chi-squared tests and Cox's models. Univariate analysis showed that the indicators of slow-healing GU were ulcer size (P=0.002) and persisting ulcer symptoms (P=0.0001); indicators of slow-healing DU were ulcer size (P=0.0001), persisting ulcer symptoms (P=0.0001), alcohol (P=0.0003), and NSAID (P=0.0088) consumption. DU patients taking antiplatelet drugs have significantly better results after four weeks and worse results after eight weeks (P=0.0352). Cox's models revealed that the persistence of ulcer symptoms is the most important factor predicting unhealing ulcers (GU,P=0.0008; DU,P=0.0002), while ulcer size is only important for DU (P=0.0215). Patients with ulcer disease onset before 65 years of age were more frequently males; DU subjects were more frequently smokers, with a family history of ulcer and no NSAID consumption. In conclusion, persistence of ulcer symptoms and ulcer size are indicators of slow-healing ulcer in the elderly; in the case of DU, NSAID and alcohol consumption may be additional factors.

1. The authors investigated the effect of two extrahepatic cholestasis models (one by bile duct ligation and the other by choledocho-jugular fistula) on the hepatic clearance of horseradish peroxidase in male Sprague-Dawley rats divided into four groups. 2. In groups A (n = 5 rats) and B (n = 5), bile duct ligation was performed, while a choledocho-jugular fistula was created in groups C (n = 5) and D (n = 7). A 10 mg intravenous bolus of horseradish peroxidase was injected after 24 h (groups A and C), 48 h (groups B and D) or 1 h (Group E; five sham-operated rats). Serum and bile samples were then serially collected for 2 h. 3. In all groups, serum horseradish peroxidase levels increased soon after injection and then rapidly decreased, the curves being similar. Biliary excretion increased for 30 min and then slowly decreased. The highest horseradish peroxidase biliary concentrations and outputs were found in Group B followed by Group A; both groups had significantly higher levels than Group E. No difference was found between horseradish peroxidase biliary excretion of groups C and D and that of sham-operated rats. 4. When each group was considered separately, sampling times correlated with the corresponding ratios of bile/plasma HRP. Significant differences were found between the relative slopes of groups A, B and E, but not between those of groups C, D and E. 5. In conclusion, bile duct obstruction greatly affects the plasma-bile transfer of fluid phase markers, such as horseradish peroxidase, while single retention, caused by choledocho-jugular fistula, has no influence.(ABSTRACT TRUNCATED AT 250 WORDS)

To verify whether improvements in hygiene affect the risk of HBV infection, a seroepidemiological survey on HBV infection was carried out in a home for the elderly with continuous-care accommodation. HBV serum markers were tested in 315 subjects and the results of HBV infection were compared to those observed in two different types of nursing homes for the elderly from an earlier seroepidemiological study carried out in 1978. In addition, results from a cohort of a pre-geriatric population living in their own homes in the same geographical area surveyed in 1980 were compared to the present study. A statistically significant lower prevalence of HBV serum markers in the new home for the elderly compared to the two types studied in 1978 was observed. No difference was found between the new institutionalized study group and the cohort of a pre-geriatric population surveyed in 1980. These results reflect the improved sanitation in homes for the elderly and show that the elderly have very few opportunities to become infected, even in a close cohabitation system.

Recent reports indicate that hepatitis C virus (HCV) may play a role in the pathogenesis of hepatocellular carcinoma in cirrhotics. Using an ELISA test, we evaluated the prevalence of anti-HCV antibodies in 97 patients with hepatocellular carcinoma (HCC) in cirrhosis and in a group of 223 patients, including: 49 patients with HBsAg-positive chronic liver disease (CLD), 42 with alcoholic CLD, 110 with cryptogenic CLD and 22 with post-transfusional HBsAg-negative CLD. All diagnoses were histologically confirmed. Overall, anti-HCV-positive HCC were 64% of the total, with no statistically significant difference with respect to CLD (60.9%). The prevalence of anti-HCV was higher in cryptogenic HCC (80%) than in HBsAg-positive (60%) or alcoholic HCC (42.8%) (p less than 0.005). When HCC and cirrhosis of similar putative etiology were considered, anti-HCV prevalence was significantly higher in HCC than in cirrhosis only in the groups of patients with alcoholic liver damage (60% in HCC vs. 38% in cirrhosis, p less than 0.005). In HBsAg-positive patients, anti-HCV prevalence was twice as high in HCC than in CLD, but the difference was not statistically significant. Overall, anti-HCV prevalence in HCC was significantly higher than in alcoholic or HBsAg-positive CLD (p less than 0.001 and p less than 0.01, respectively) but lower than in cryptogenic CLD (p less than 0.001). Association between anti-HCV and anti-HBc was significantly more prevalent in patients with CLD than in those with HCC.(ABSTRACT TRUNCATED AT 250 WORDS)

This experimental and clinical study examined the relationship between oesophageal damage and optimal pH of refuxate, and whether 24-h pH monitoring at optimal pH could discriminate the severity of oesophagitis. The rabbit oesophagus was perfused in vivo with pepsin and hydrochloric acid solutions of difering pH for 60 min. Maximal oesophageal damage coincided with peptic solutions at pH 1.5–2.5. Fifty-nine patients with proven gastro-oesophageal reflux disorders were tested for manometric features of the lower oesophageal sphincter (Pressure, overall length and abdominal length) and oesophageal exposure to different pH levels. They were classified into four groups according to the endoscopically demonstrated severity of oesophagitis. Supine exposure at the optimal pH level for pepsin activity (pH 1.5–2.5) and overall sphincter length were found to discriminate the severity of oesophagitis reliably in 75 per cent of cases.

This study was performed to investigate modifications in the serum bilirubin forms, hepatobiliary enzymes, and some glycoproteic substances in patients during the course of extrahepatic cholestasis (stage A) and following its clinical resolution (stage B). The series consisted of 16 patients 11 had main bile duct stones; two, benign stenosis of the main bile duct; and three, main bile duct cancer. Cholestasis resolved spontaneously in one case, under endoscopy in two, and following surgery in 13. Five patients with liver cirrhosis and a picture of intrahepatic cholestasis following anesthesia were also investigated. Serum bilirubin forms were measured using van den Bergh's method and the alkaline methanolysis-HPLC procedure; the mono- and di-conjugated forms were considered together in the overall evaluation of the results. The hepatobiliary enzymes (ALP, GGT, and AST) were increased at stage A and significantly decreased at stage B. Similar patterns were observed in total (TB), unconjugated (UB), and conjugated bilirubin (CB) and in the percentage of CB out of TB (% CB). In the majority of patients, % CB at stage B was lower than at stage, whereas in subjects with a high initial UB value, a different % CB pattern was observed. The direct bilirubin percentage (% DB), on the other hand, had a different pattern, and the variations between stages A and B were not significant. The pathophysiological bilirubin pattern was similar in patients with intrahepatic cholestasis. At stage A, in a number of patients the levels of glycoproteic substances (CA 19-9, TPA and ferritin) were raised, but at stage B they tended to decrease towards the normal range. Correlations were found between CA 19-9 or TPA variations and cholestasis indicators. It may be concluded that our HPLC technique may reveal differences in the behavior of the bilirubin pigments that cannot be detected with van den Bergh's method, even in the presence of similar TB variations. The increase in the glycoproteic substances considered may express an impairment in their metabolic (largely hepatic) clearance, as occurs in the cholestatic setting.

Numerous factors seem to affect zinc absorption. Gastric acid secretion has been demonstrated to facilitate iron absorption. The zinc tolerance test (ZTT with ZnSO4 220 mg p.o.) was performed in 11 healthy volunteers to study the effects of administering the acid secretion inhibitor cimetidine (1 g/day p.o. for 3 days) and to evaluate the influence of HCl gastric secretion on zinc absorption in physiological conditions. Zinc absorption was reduced after cimetidine administration (p less than 0.005), suggesting that gastric pH influences zinc absorption. To rule out any direct effect of the drug on zinc absorption in five other healthy adults we further evaluated zinc absorption by using a different H2 antagonist (ranitidine 300 mg/day for 3 days and 300 mg before the test). Cimetidine was also tested in these subjects at half the dosage administered to the first group of subjects. Gastric acidity was monitored at 60-min intervals throughout the test via a nasogastric tube. The areas under the plasma concentration curves for zinc were significantly reduced after ranitidine (p less than 0.01), but not after cimetidine administration. Gastric acid was also reduced after ranitidine, but not after cimetidine (500 mg) administration, suggesting that gastric acid secretion plays a role in the regulation of zinc absorption in man.

In the present study efforts are made to obtain a correlation between the trace element (TE) levels in patients and the presence of digestive cancer. The aim of the study is to detect selenium (Se), zinc (Zn) and other TE concentrations in different segments of colonic mucosa and to find out if there is any difference between the normal and pathological colonic mucosa. The concentration data (averages, standard deviations and ranges) obtained by neutron activation analysis and proton induced X-ray emission are presented and the data distribution is analyzed.

Variations in urinary kallikrein in pancreatic diseases were ascertained, and possible influencing factors were investigated. Serum amylase and urinary excretion of glandular kallikrein, pancreatic ribonuclease (RNase), gamma-glutamyltransferase (GGT) and amylase were measured in 24 control subjects, 39 patients with pancreatic cancer, 49 with pancreatitis and 63 with extra-pancreatic diseases. Urinary kallikrein was found to be elevated in a substantial number of patients with pancreatitis. Higher levels were detected in patients with a relapse, which was diagnosed using clinical and biochemical examinations. RNase was also increased in a high number of patients with pancreatic diseases, but was not correlated with pancreatic damage. In patients with pancreatitis, a correlation was found between urinary kallikrein and RNase excretions. No correlations were found between kallikrein and serum or urinary amylase and GGT. We can conclude that urinary kallikrein excretion increases in pancreatitis, especially when a phlogistic involvement of the pancreas is present; this condition may lead to a release of this ultrafiltrable enzyme in the circulation. Renal tubular damage, which determines a reduced reabsorption of this enzyme, seems to play a concomitant but minor role in this process.

Liver abnormalities seem a very rare association in Turner’s syndrome, only reported in a few anecdotal cases. We report the clinical and morphological findings in 3 patients who presented with cholestasis. One of them had a definite diagnosis of primary sclerosing cholangitis, in whom the natural history was complicated by the development of two distinct tumors. A review of the few cases described in the literature and our own case reports support the hypothesis that liver disease in Turner’s syndrome may have a variety of expressions including cholestasis.

AIM: To evaluate the long-term histological outcome of patients transplanted for HBV-related liver disease and given HBIg prophylaxis indefinitely after LT. METHODS: Forty-two consecutive patients transplanted for hepatitis B were prospectively studied. HBsAg, HBV-DNA and liver function tests were evaluated in the serum 3, 6 and 12 mo after LT and then yearly. LB was obtained 6 and 12 mo after LT and yearly thereafter. Chronic hepatitis (CH) B after LT was classified as minimal, mild, moderate or severe. RESULTS: HBV recurred in 7/42 (16.6 %) patients after 6-96 mo of follow-up. A hundred and eighty-seven LB were evaluated. Four of 7 patients with graft reinfection, all with unknown HBV DNA status before LT, developed cirrhosis at 12-36 mo of follow-up. Of the 122 LB obtained from 28 HBsAg+/HCV- recipients with no HBV recurrence after LT, all biopsies were completely normal in only 2 patients (7.1 %), minimal/non-specific changes were observed in 18 (64.2 %), and at least 1 biopsy showed CH in the remaining 8 (28.5 %). Twenty-nine LB obtained from 7 patients transplanted for HBV-HCV cirrhosis and remaining HBsAg- after LT revealed recurrent CH-C. Actuarial survival was similar in patients with HBsAg+ or HBsAg- liver diseases. CONCLUSION: Though protocol biopsies may enable the detection of graft dysfunction at an early stage, the risk of progression and the clinical significance of these findings remains to be determined.

Background: Students have a positive attitude to organ donation and transplantation, usually associated with their personal willingness to donate their organs after death. The aim of this study was to evaluate the opinions of university students on transplantation and organ donation, at a single Italian university. Methods: University undergraduates attending the first year on five different courses in 2001 were surveyed at Padua University by using an anonymous 13-item questionnaire. Results: 97.2% of the students completed the questionnaire (77.4% females, mean age 20.4 yr); they were attending Medicine (33.8%), Agriculture (5.9%), Veterinary Medicine (11.4%), Psychology (18.5%) and Educational Sciences (30.4%). The majority was aware of the problem of the paucity of organ donations and deaths on the waiting list in Italy. Most students would accept transplantation in the case of a human donor (97%), an artificial organ (95%) or an animal donor (76%); and 87% of them were prepared to donate their own organs after death. No differences were seen when students attending science courses were compared with those attending art courses. Italian university students have a very positive attitude and willingness to donate their own organs after death, with no differences emerging as regards type of university education.

Alternative approaches to overcome the shortage of donors for liver transplantation may be the use of hepatocytes for bioartificial devices or transplantation. Therefore, the setting-up of new in vitro culture techniques allowing the long-term survival and functional maintenance of hepatocytes represents a formidable challenge. Aim of this study was to obtain a liver homologous acellular matrix (HAM) able to support viability and metabolic functions of rat hepatocytes in primary culture. HAMs were prepared by sequential incubation of rat liver slices in deoxycholic acid and DNase solutions. Dispersed rat hepatocytes were obtained by collagenase digestion and mechanical disaggregation. Isolated hepatocytes were seeded on uncoated and collagen- or HAM-coated tissue culture plastic wells. Cultures were examined by scanning electron microscopy (SEM), and the viability of hepatocytes and their ability to produce albumin and urea were assessed. The viability of freshly dispersed hepatocytes was about 98%. Hepatocytes seeded on HAM exhibited a significantly higher viability and a markedly lower apoptotic rate than those grown on plastic or collagen. Accordingly, albumin and urea nitrogen productions were significantly higher in HAM-cultured hepatocytes. SEM showed that hepatocytes seeded on HAM displayed a clustered organization, and were well anchored to the matrix and morphologically stable. Taken together, these findings indicate that HAM strongly improves viability and functional activity of rat hepatocytes cultured in vitro.

Xenotransplantation is currently at the experimental stages on animal models and many problems still have to be overcome in the biomedical, immunological and ethical fields. Moreover, people's attitudes to xenotransplantation vary: surveys among intensive-care staff have revealed negative opinions, while the general public and students seem to be more positive. Little is known about the influence of schooling and the choice of university faculty on attitudes to xenotransplantation. The aims of this study were: (i) to evaluate university students’ attitudes to xenotransplantation; (ii) to investigate any socio-demographic, religious and educational determinants behind students’ opinions on xenotransplantation. University undergraduates on five different courses were surveyed at Padua University. A 24-item questionnaire was distributed to students at the end of lectures and completed anonymously immediately after its distribution. No information was given to students beforehand. Statistical analysis: chi-squared, Pearson's test; P-values

Long-term persistence of specific antibodies after primary immunization against HBV infection has been reported. In this study, we evaluated the persistence of anti-HBs in vaccinees 6 years after primary immunization and the response to a booster dose using a recombinant DNA yeast-derived HB vaccine. An 85.4% seroprotection rate was observed after 6 years with a significantly higher seroprotective rate in those subjects who received four doses of vaccine primary immunization as compared with those who received three doses (93.9% versus 67.2%, p < 0.001). One month after receiving the booster dose, 98.6% of the subjects had an anamnestic type of response. The GMTs were found to decrease progressively with increasing age. The antibody levels after booster dose were higher than those attained at the end of primary immunization and reflected the trend seen before the administration of the booster. These results are consistent with the existence of an effective immunological memory in HB vaccine responders. Subjects who received four doses during primary immunization were better seroprotected and had a higher seroprotection rate after the booster dose.

Common etiopathogenic factors may explain the association of systemic sarcoidosis with inflammatory bowel disease.We report two cases of such an association: one of sarcoidosis that developed 2 years after proctocolectomy for ulcerative colitis and one of sarcoidosis and Crohn's colitis. Factors like increased cellular immunity or circulating immunocomplexes or autoantibodies may have a role. Exogenous agents or familiarity may also be involved.It is postulated that the association between sarcoidosis and inflammatory bowel disease (both ulcerative colitis and Crohn's disease) does not occur by chance alone and that the two conditions may share some genetic or immunologic alterations. The two diseases, however, follow an independent clinical course.

BACKGROUND: A more rapid and aggressive course of hepatitis B virus (HBV)-related and hepatitis C virus (HCV)-related infection in organ transplant recipients has been described. Interferon alfa is the most accepted drug for treating HBV and HCV chronic infections. However, the use of interferon alfa-N3 has been contraindicated in heart transplant (HTx) recipients because of the hypothesized greater risk of triggering acute cellular rejection. The aim of this clinical pilot study was to evaluate tolerability, safety, and efficacy of natural leukocyte interferon alfa in the treatment of chronic HBV and HCV in HTx recipients. METHODS: Seven HTx recipients were enrolled in the study: two with HBV, four with HCV, and one with combined HBV-HCV chronic infection. The patients had a mean follow-up after heart transplantation of 8.5+/-3 years, before starting interferon alfa-N3 treatment at a dose of 6 MU three times per week, intramuscularly for 12 months. RESULTS: All patients completed the treatment with no major side effects. No unexpected episodes of acute cellular rejection were observed during the treatment. Mean aminotransferase serum levels were significantly lower than before transplantation at 3 (P

Background: Hepatitis C recurring after orthotopic liver transplantation varies in severity and some patients rapidly develop fully established liver cirrhosis. Neither clinical nor biological markers of such rapid cirrhotic evolution are available. Aim: To assess the value of histology in identifying patients who will develop cirrhosis shortly after liver transplantation. Patients and methods: Only cases of recurrent hepatitis C diagnosed by both hepatitis C virus-RNA positive serum and liver changes consistent with hepatitis, with no other causes of allograft injury, were considered. A total of 128 liver biopsies were scored from 29 consecutive patients with a mean follow up of 48 (13.97) months. The histological activity index was evaluated according to Ishak et al . The time of the first histological diagnosis of recurrent hepatitis C in the absence of rejection was defined as time of histological recurrence (RHC-T). Results: First histological diagnosis of recurrent hepatitis with no features of rejection was obtained at the six month biopsy in 23 of 29 cases. By the end of follow up, nine patients had developed cirrhosis (mean follow up 38 (14.39) months (range 18–60)). The remainder (mean follow up 46 (13.40) months (24–72)) showed a spectrum of fibrosis but no cirrhosis. Severe necroinflammatory lesions at RHC-T significantly correlated with rapid development of cirrhosis. At the RHC-T biopsy, only cases evolving into cirrhosis showed confluent necrosis. The median value of the histological activity index was 11 (mean 11.11 (1.76) (range 9–14)) in patients who developed cirrhosis and four (mean 4 (1.78) (range 1–8)) in the others (p