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Background: An association between monoclonal gammopathies and chronic liver diseases has been reported. Objective: To determine the prevalence of monoclonal gammopathies in patients with chronic hepatitis C virus (HCV) infection and the possible association of monoclonal gammopathies with HCV genotypes. Design: Prospective study. Setting: Departments of internal medicine and hematology at two university hospitals in Italy. Patients: 239 HCV-positive and 98 HCV-negative patients with chronic liver diseases were recruited consecutively. Measurements: Clinical data were gathered, liver histologic examination was done, serum immunoglobulin and cryoglobulin levels were measured, and immunoelectrophoresis was done for monoclonal component detection. Patients with monoclonal gammopathy had serum HCV RNA measured and HCV genotype determined by polymerase chain reaction and had histologic examination of bone marrow. Results: Monoclonal band was detected in 11% of HCV-positive patients and in 1% of HCV-negative patients (P = 0.004). The prevalence of HCV genotype 2a/c was higher in patients with monoclonal gammopathies than in those without (50% compared with 18%; P = 0.009). Conclusion: The prevalence of monoclonal gammopathies in patients with HCV-related chronic liver disease is striking and is often associated with genotype 2a/c infection., Some people infected with the hepatitis C virus (HCV) have a monoclonal gammopathy and it appears to be caused by a specific strain of the virus. Monoclonal gammopathy is caused by a proliferation of B cells, which are the immune cells that produce antibodies. Researchers tested 239 HCV-positive people and 98 HCV-negative people for monoclonal gammopathy. Eleven percent of the HCV-positive people had the disease compared to 1% of those who were HCV-negative. Half of those with the disease were infected with the 2a/c viral strain compared ot 18% without the disease.

The current study evaluated the effect of five yeast-derived formulations (T1–T5) on microbial metabolism and composition of the canine and feline gut microbiota using a novel in vitrocolonic incubation approach. This novel in vitromodel allowed for growth of the entire spectrum of dog- and cat-derived bacteria from the inoculum, thus offering an excellent platform to evaluate effects of nutritional interventions on the gut microbiota. Further, yeast-derived ingredients differentially increased production of acetate, propionate, butyrate, ammonium, and branched short-chain fatty acids, with T5 and T1 consistently stimulating propionate and butyrate, respectively. 16S-targeted Illumina sequencing coupled with flow cytometry provided unprecedented high-resolution quantitative insights in canine and feline microbiota modulation by yeast-derived ingredients, revealing that effects on propionate production were related to Prevotellaceae, Tannerellaceae, Bacteroidaceae, and Veillonellaceae members, while effects on butyrate production were related to Erysipelotrichaceae, Lachnospiraceae, Ruminococcaceae, and Fusobacteriaceae. Overall, these findings strengthen the health-promoting potential of yeast-derived ingredients.

Background Intrahepatic cholangiocarcinoma (ICC) is the second most common primitive liver cancer and is rising in incidence worldwide. Given its low survival and resectability rates, locoregional therapies such as Yttrium-90 transarterial radioembolization (Y-TARE) are increasingly being employed. This retrospective study aim was to confirm and update our previous results about overall survival (OR), safety, and efficacy of Y-TARE in patients with unresectable/recurrent ICC.Materials and Methods OS was evaluated as primary endpoint while radiological tumor response at 3 months, based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, was considered as secondary endpoint.Results Over a total of 49 patients, the overall median survival was 16 months (27-41 months, 95% confidence interval [CI]) from Y-TARE procedure. A significantly longer survival was recorded in naive patients compared to patients previously submitted to any type of liver-directed treatment and radical surgery (18 vs 14 months, P=.015 and 28 vs 14 months, P=.001, respectively). Target lesion and overall objective response for RECIST 1.1 criteria were 64.6% and 52.1%, respectively. Low rates of postprocedural and late complications were recorded.Conclusions In unresectable and recurrent ICC, Y-TARE confirms its safety and its potential in increasing OS, especially in naive patients.

Gut microbiota promotes healthy effects on the host and prevents diseases. Probiotic (probios, for life) are defined as “live microorganisms which when administered in adequate amounts confer a health benefit on the host.” At the beginning of 1900s Louis Pasteur identified the microorganisms responsible for the process of fermentation, whereas E. Metchnikoff associated the enhanced longevity of Bulgarian rural people to the regular consumption of fermented dairy products such as yogurt. He suggested that lactobacilli might counteract the putrefactive effects of gastrointestinal metabolism that contributed to illness and aging. Hippocrates declared, 2000 years earlier, that “death sits in the bowels.” Metchnikoff considered the lactobacilli as probiotics (“probios,” conducive to life of the host as opposed to antibiotics); probiotics could have a positive influence on health and prevent aging. During the neolitic period of the age of the stone, the domestication of animals occurred and man began to get fermented food. Probably serendipitous contaminations in favorable environments played a major role. Fecal microbiota transplantationdates to a fourth-century Chinese handbook for food poisoning or severe diarrhea. To date fecal transplant cures Clostridium difficileinfections with more efficacy than vancomycin, and prevents recurrence.

Left atrial (LA) dilation precedes or appears early after the onset of atrial fibrillation (AF) and factors in perpetuating the arrhythmia. Angiotensin receptor blockers were proposed for reversing LA remodeling. We evaluated the effect of valsartan on LA remodeling in patients with a recent episode of AF and the effect of LA size on AF recurrence (AFr).

Alcoholic liver cirrhosis (ALC) is a leading indication for orthotopic liver transplantation (OLT).

Orthotopic liver transplantation (OLT) for end-stage liver disease resulting from hepatitis B virus (HBV) infection is associated with a high rate of recurrence and reduced survival. Lamivudine is effective in inhibiting HBV replication in patients with chronic hepatitis. This study evaluated the impact of lamivudine on viral suppression, liver function, and disease severity in patients awaiting OLT with HBV e-minus strain infection.

BACKGROUND: The role of interferon treatment on the natural history of hepatitis C virus related cirrhosis is under debate. AIM: To evaluate the effect of interferon on the clinical course of compensated hepatitis C virus related cirrhosis. PATIENTS AND METHODS: Seventy two cirrhotic patients treated with interferon and 72 untreated controls matched treated patients with for quinquennia of age, sex, and Child-Pugh's score were enrolled in a prospective non-randomised controlled trial. Treated patients received leucocytic interferon alfa, with an escalating schedule for 12 months. The incidence and risk (Cox regression analysis) of clinical complications (hepatocellular carcinoma, ascites, jaundice, variceal bleeding, and encephalopathy) and death were calculated. RESULTS: Over median follow up periods of 55 months for treated and 58 for untreated subjects, seven and nine patients, respectively, died, and 20 and 32, respectively, developed at least one clinical complication (ns). Hepatocellular carcinoma developed in six treated and 19 untreated patients (p=0.018). Seven treated patients showed sustained aminotranferase normalisation and none died or developed complications. Clinical complications were significantly associated with low albumin, bilirubin, and prothrombin activity while hepatocellular carcinoma was significantly related to no treatment with interferon, oesophageal varices, and high alpha fetoprotein levels. By stratified analysis, the beneficial effect of interferon was statistically evident only in patients with baseline alpha fetoprotein levels > or =20 ng/ml. CONCLUSIONS: Interferon does not seem to affect overall or event free survival of patients with hepatitis C virus related cirrhosis while it seems to prevent the development of hepatocellular carcinoma. Patients who achieved sustained aminotransferase normalisation survived and did not develop any complications during follow up.

In the present study, high levels of CD30s, a glycoprotein preferentially expressed and released by T lymphocytes producing Th2-type cytokines, were seen in the sera of patients with chronic hepatitis C, and a correlation with histological activity of the disease was found. CD30s levels were assayed in the sera of 29 HCV RNA-positive patients with histologically proven chronic active hepatitis and in 30 healthy blood donors. Thirteen of 29 (45%) HCV patients had CD30s serum levels above the normal range (>20U/ml). Mean CD30s serum levels were significantly higher in HCV patients than in controls (P<0.0005). A positive correlation was found between serum CD30s levels and both the histological activity index (r=0.59, P=0.001) and ALT serum levels (r=0.5;P=0.006). The raised CD30s level found in more severe HCV liver disease indirectly suggests activation and expansion of Th2cells. CD30s levels could represent a useful surrogate marker of activity in chronic HCV infections.

The effects of interferon therapy on hepatitis C virus (HCV) genome are still controversial in terms of biological and clinical significance. Changes in the quasispecies of the hypervariable (HVR) and non‐structural 5A (NS5A) regions of HCV 1b were evaluated in nine patients treated with increasing doses of interferon and five untreated controls. HCV quasispecies were analyzed in HVR and NS5A by single‐strand conformation polymorphism assay. The HVR quasispecies varied over time both in treated and untreated patients. However, at least one persistent strain was present in all patients. With low doses of interferon, variations in HVR complexity were found in seven of nine patients and in four patients new variants became detectable. A reduction in the heterogeneity of the HVR quasispecies was observed after increase of the interferon dose. In contrast, NS5A profiles remained unmodified in all but three cases in which direct sequencing showed no changes in amino acid sequences of the predominant strain. The results suggest that interferon sensitivity of some HCV strains may be dose dependent. The homogeneity of NS5A pattern populations during treatment suggests that interferon exerts much less pressure on this region. J. Med. Virol. 60:133–138, 2000. © 2000 Wiley‐Liss, Inc.

The highly purified alpha-amylase from Tenebrio molitor L. larva (yellow mealworm) reversibly combines with two closely related homogeneous glycoprotein inhibitors, one dimeric (termed ‘inhibitor 0.19’) and one monomeric (termed ‘inhibitor 0.28’), from wheat flour. As established by means of difference spectroscopy and kinetic studies, molar combining ratios for the amylase–inhibitor-0.19 and amylase-inhibitor-0.28 complexes were 1:1 and 1:2 respectively. Two amylase–inhibitor-0.19 complexes with slightly different retention volumes on Bio-Gel P-300 and only one amylase–inhibitor-0.28 complex were observed. Dissociation constants of the amylase–inhibitor-0.19 and amylase–inhibitor-0.28 complexes were 0.85 nM and 0.13 nM respectively. A strong tendency of both complexes to precipitate under an ultracentrifugal field was observed; the minimum molecular weight calculated for the two complexes under such conditions was approx. 95 000. The two complexes showed difference spectra indicating involvement of structurally related or identical tryptophyl side chains in the binding of inhibitors 0.28 and 0.19 to the amylase. A model summarizing the main features of the inhibition of the insect amylase by the two wheat protein inhibitors is proposed.

Summary Amylase from chicken pancreas was purified by an affinity method involving filtering a crude extract from pancreas through a Sepharose-wheat albumin column and eluting the retained enzyme with maltose. The purified amylase showed two active bands upon polyacrylamide electrophoresis in an alkaline buffer system and only one band in an acidic buffer system. The enzyme is a Ca2+—glycoprotein which behaves as a typicala-amylase. It consists of a single polypeptide chain with molecular weight 53,000 and contains 5.3 moles of reducing sugars per mole of protein. Optimal conditions of pH and temperature for the enzymic activity are 7.5 and 37°C. The enzyme is irreversibly inactivated by removal of Ca2+ by exhaustive dialysis and is activated by the presence in the assay mixture of Cl-; other halides are less effective than Cl- in activating the enzyme.

A peptic-tryptic-cotazym (PTC) digest of a crude wheat gliadin preparation was obtained under experimental conditions simulating in vivoprotein digestion and then fractionated into 10 peaks by ion-exchange chromatography. PTC-gliadin digest and one of its subfractions (coded as fraction 9 according to its elution pattern) were very active in inhibiting in vitrodevelopment and morphogenesis of small intestine from 17− and 18-day-old rat fetuses, whereas they were harmless for the culture of jejunum from 21-day-old fetuses. PTC-digest also induced extensive tissue degeneration and necrosis of in vitrocultured small intestinal mucosa from patients with active celiac disease (gluten-induced entheropathy), but did not cause any detectable effect on histolog-ically normal human small intestinal mucosa. Some wheat albumin and gliadin fractions were also tested on in vitrodeveloping small intestine from 17-day-old rat fetus. Among all the tested protein fractions, only one gliadin fraction (coded as αio-gliadin from its gel electrophoretic mobility) exhibited a toxic effect; morphologic alterations induced by αio-gliadin were similar to those induced by PTC-digest and fraction 9.

To examine the relationship between smoking and myocardial infarction in women.

Serum amylase and lipase concentrations weredetermined in 78 patients with chronic liver diseases[26 chronic active hepatitis (CAH) and 52 livercirrhosis] and in 15 healthy subjects. Pancreaticisoamylase concentrations and macroamylase complexes wereassayed in hyperamylasemic sera. Serum amylase levelswere abnormally elevated in 27 patients (35%; 22 livercirrhosis, 5 CAH), whereas serum lipase levels were elevated in 16 patients (21%; 15 livercirrhosis, 1 CAH). In 9 of the 27 hyperamylasemicpatients, the hyperamylasemia was of pancreatic type.Macroamylasemic complexes were not detected inhyperamylasemic sera. Patients with liver cirrhosis had serumlevels of amylase and lipase significantly higher thanboth the healthy subjects and the patients with CAH,while no significant differences were found in serum levels of these enzymes in patients with CAH ascompared to the healthy subjects. A decreased livermetabolism of serum amylase and lipase in patients withchronic infective liver disease, especially in those having liver cirrhosis, may lead to anaccumulation of these enzymes in the blood.

The relationship between various diseases and immunisations and the risk of multiple myeloma was analysed using data from a hospital-based case-control study conducted in Northern Italy on 117 patients with multiple myeloma and 477 controls. Associations were observed for clinical history of scarlet fever (relative risk, RR = 2.0; 95% confidence interval, CI = 1.1-3.9), tuberculosis (RR = 2.3%; 95% CI = 0.9-5.7) and BCG immunisation (RR = 3.0; 95% CI = 1.4-6.4). The relative risk was 1.8 (95% CI = 0.9-3.5) for episodes of Herpes zoster infection, but most of the excess cases occurred within 10 years of diagnosis, suggesting that this might have been an early manifestation of the disease. No association emerged for common childhood viral infections or any other immunisation practice. When various classes of infectious or inflammatory diseases were grouped together according to their aetiology, there was a significant positive association with chronic bacterial illnesses (RR = 1.8; 95% CI = 1.1-2.8), and the relative risk estimates increased with the number of bacterial diseases. The trend in risk with number of diseases was significant (chi 21 = 4.5, P = 0.03). A negative association was found between allergic conditions and risk of multiple myeloma (RR = 0.6; 95% CI = 0.3-1.0).

Summary: A peptic-tryptic-cotazym (PTC) digest of a crude wheat gliadin preparation was obtained under experimental conditions simulating in vivo protein digestion and then fractionated into 10 peaks by ion-exchange chromatography. PTC-gliadin digest and one of its subfractions (coded as fraction 9 according to its elution pattern) were very active in inhibiting in vitro development and morphogenesis of small intestine from 17- and 18-day-old rat fetuses, whereas they were harmless for the culture of jejunum from 21-day-old fetuses. PTC-digest also induced extensive tissue degeneration and necrosis of in vitro cultured small intestinal mucosa from patients with active celiac disease (gluten-induced entheropathy), but did not cause any detectable effect on histolog-ically normal human small intestinal mucosa. Some wheat albumin and gliadin fractions were also tested on in vitro developing small intestine from 17-day-old rat fetus. Among all the tested protein fractions, only one gliadin fraction (coded as a10-gliadin from its gel electrophoretic mobility) exhibited a toxic effect; morphologic alterations induced by a10-gliadin were similar to those induced by PTC-digest and fraction 9.Speculation: Peptides obtained from wheat gliadins under in vitro conditions simulating protein digestion by humans as well as whole wheat gliadin are very active in damaging in vitro developing jejunum from 17- and 18-day-old rat fetuses, but have no toxic effect on the culture of jejunum from 21-day-old rat fetus. The transient character of such an effect is suggestive of a protective mechanism against the toxic protein components from wheat, associated with the age-dependent maturation of rat intestinal mucosa. It is speculated that also human normal intestine develops with maturation similar specific detoxifying mechanisms and that wheat gliadin and gliadin-derived peptides might exert a toxic action when human intestinal mucosa is not yet fully mature (i.e., during early extrauterine life) or when adult human mucosa regresses towards immature steps of development (i.e., in intestinal diseases with mucosal atrophy).

In animal models hematopoietic stem cells (HSCs) and the hematopoietic cytokine granulocyte colony-stimulating factor (G-CSF) contribute to tissue regeneration after acute or chronic liver damage. In this study, we assessed whether: 1) G-CSF can be safely administered to patients with liver cirrhosis to expand and mobilize HSCs into peripheral blood; 2) G-CSF treatment affects residual liver function. Eighteen patients with a Child-Turcotte-Pugh (CTP) score < 10 and a Mayo Model for End Stage Liver Disease (MELD) score < 20 were considered eligible for the study. Increasing doses of G-CSF were administered subcutaneously for 7 consecutive days to 5 cohorts of 3 patients each, starting from 2.2 μg/kg/daily, until the achievement of the maximum-tolerated dose and/or the successful mobilization of ≥10 CD34+ cells/μl in at least 2/3 patients. G-CSF mobilizing dose was found at 15 μg/kg/day. Four additional patients were treated with the mobilizing G-CSF dose. All of them showed a successful mobilization of HSCs with a median peak value of CD34+ and CD133+ cells of 27.1(±15.5) and 15.2 (±5.1)/μl, respectively. Circulating HSCs were then collected by single volume leukapheresis and a median of 1.4(±0.73)x106 CD34+ HSCs/kg body weight were cryopreserved. G-CSF treatment induced a significant increase of hepatocyte growth factor serum level. When we analyzed stem cell subsets, we found significant mobilization of early hematopoietic (CD34+/CD38−) and endothelial (CD34+/KDR+, CD133+/KDR+) progenitors as well as CD34+/CXCR4+ cells. No severe adverse events were observed at any dosage or during leukapheresis. According to CTP and MELD score, no significant modification of liver function was observed during the treatment period and follow up (median=198 days) in both mobilizing and non-mobilizing patients. Nevertheless, in all treated patients a significant reduction of alpha-fetoprotein values was observed (p<0.001). In conclusion, the administration of G-CSF to patients with liver cirrhosis is safe, feasible and capable of mobilizing HSCs at the dosage of 15 μg/kg/day. Our study represents the first step for evaluating the role of G-CSF and mobilized HSCs to improve liver function in patients with liver cirrhosis.

We assessed prevalence and risk factors for human immunodeficiency virus (HIV) infection in 637 patients (506 men, 131 women; median age 30 years, range 17–64) attending between September 1988 and July 1989 for the first time two sexually transmitted disease (STD) clinics in Northern Italy, for suspected or STD treatment. A total of 44 subjects (6.9%, 95% confidence interval, (CI): 4.9–8.9) were seropositive for HIV antibodies. The prevalence of HIV infection decreased with age, from 9% in patients aged 24 years or less to 3% in those aged 45 years or more (x2, trend 4.97, p<0.05). Women tended to have a lower prevalence of infection then men (5.3% versus 7.3%) but this was not statistically significant. Compared with men reporting no homosexual intercourse, HIV infection risk was about 50% higher in those reporting bisexual intercourse (age- and sex-adjusted odds ratio (OR) 1.5, 95% CI: 0.6–3.6) and about fourfold in those reporting only homosexual intercourse (OR 3.8, 95% CI: 1.7–8.5). No clear trend in risk was observed with number of sexual partners both in men and in women. Intravenous drug users had an increased risk of HIV infection; compared with non-users, the OR was 5.6 (95% CI: 3.0–10.5) in users, and the point estimates increased with frequency of use, from 3.3 (95% CI: 0.8–11.5) in occasional users to 6.4 (95% CI: 3.2–12.8) in regular users. The risk of HIV infection was 2.2 (95% CI: 1.1–4.3) in patients reporting a history of STD, and 1.6 (95% CI: 0.8–3.3) in those reporting syphilis. The results of treponema pallidum haemogglutination assay (TPHA) and veneral disease reference laboratory (VDRL) assays were consistent with the latter finding: patients with positive TPHA and VDRL tests had a risk of HIV infection respectively of 2.0 (95% CI: 1.0–4.2) and 2.7 (95% CI: 1.4–5.4); these associations however were not found in intravenous drug users.