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Biomedical subjects

P Almasio

Publications and source records attributed to P Almasio.

At least 55 records · Page 3Linked to original sources

Serum hepatitis C virus (HCV)-RNA and response to alpha-interferon in anti-HCV positive chronic hepatitis.

Hepatitis C virus (HCV) replication was assessed before and during alpha-interferon (IFN) treatment in 22 anti-HCV positive patients with posttransfusion or sporadic chronic hepatitis (CH). Eleven patients were "responders" and 11 patients "non-responders" to IFN. Thirteen anti-HCV negative healthy subjects and five anti-HCV negative patients with autoimmune CH served as controls. Serum HCV-RNA was detected by the polymerase chain reaction (PCR) in all untreated anti-HCV positive patients but in none of the anti-HCV negative subjects. PCR primers from the 5'-noncoding (NC) region were more sensitive than primers from a non-structural (NS5) region in detecting HCV-RNA (21/22, 95% vs. 7/22, 32%, respectively). Positive strand HCV-RNA titre and positivity rate for the negative strand were similar in responders and non-responders before IFN treatment, as well as anti-c100-3 titre by enzyme-linked immunosorbent assay (ELISA), and anti-5-1-1, anti-c33c, anti-c22 positivity rate by immunoblot assay (RIBA). HCV-RNA positivity by both NC and NS primers was more frequent before IFN among responders. During IFN treatment, serum HCV-RNA was detectable, mostly at low titres, in 1 (NC positive) of the 11 responders and in 9 (4 NS positive and 5 NC positive) of the 11 non-responders. Among the four non-responders who were NS positive during IFN, three were NC positive before IFN. Serum HCV-RNA was always found in our post-transfusion or sporadic anti-HCV positive patients with CH. Viraemia generally decreased during IFN treatment, but no available HCV markers clearly distinguished responders from non-responders before IFN treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Transmission of hepatitis B and hepatitis delta viruses in the households of chronic hepatitis B surface antigen carriers: a regression analysis of indicators of risk.

To evaluate whether clinical and laboratory features of a hepatitis B surface antigen (HBsAg) carrier can predict risks of infection, its chronicity, and the development of liver disease among close contacts, the authors studied a cohort of 994 first degree relatives or cohabitants (household contacts) of 226 non-drug-addicted chronic HBsAg carriers (index cases), of whom 77% had liver disease and 26% were superinfected by hepatitis D virus (HDV). A logistic form of regression analysis was used to assess the role of each feature in the index case as predictor of hepatitis B virus (HBV)- and HDV-related outcomes among household contacts. Six models of risk, expressed as odds ratios, were assessed by multivariate step-down analysis, with the following results. 1) Infection with HBV in the household contact was independently predicted by the index case being son, sibling, spouse, female, or HBV-DNA positive. 2) Chronic HBsAg carriage in the adult household contact was associated with female sex of the index case and with being a sibling; among young subjects, household contacts were more likely to be chronic HBsAg carriers when the index case was the mother, a sibling, or an HBV-DNA-positive subject. 3) HBV-DNA positivity in the young contact was more likely when the index case was HBV-DNA positive and when she was the mother. 4) HBV-DNA positivity in the absence of hepatitis B e antigen (HBeAg) in serum in the index case was not related to a similar pattern of infection in HBsAg-positive contacts. 5) Super-infection with HDV of an HBsAg-positive household contact was significantly predicted by female sex of the index case and by anti-HDV positivity. 6) Chronic liver disease in a contact was predicted only by HDV superinfection of the index case. We conclude that horizontal, nonparenteral transmission of HBV among siblings plays a major role in the household of HBsAg carriers from an intermediate endemicity area.

Adolescent↗

A performance evaluation of the expert system 'Jaundice' in comparison with that of three hepatologists.

The diagnostic performance of an Expert System (Jaundice) designed to discriminate between different causes of jaundice was evaluated in a test sample of 200 consecutive in-patients with serum bilirubin greater than or equal to 51 mumol/l. The average probability assigned to true diagnosis, the non-error rate and the overall accuracy were, respectively, 55%, 77% and 70%. The Expert System's discriminatory ability in probabilistic prediction, assessed by a method based on continuous functions of the diagnostic probabilities (Brier score) was good. We also compared the ability of our Expert System to that of three experienced hepatologists, who were required to give a diagnosis in 20 cases following the same protocol used by computer (i.e., by asking only clinical and laboratory items). Both the hepatologists and Jaundice achieved a correct diagnosis in 70% of 20 cases, but the Expert System asked a significantly higher average number of questions during each consultation. Analysis of the reasoning pathway made by an external referee showed a high agreement between the diagnostic strategies of the Expert System and the physicians. We conclude that Jaundice can be a useful tool to support a physician with insufficient clinical experience in this field to generate correct diagnostic hypotheses.

Diagnosis, Computer-Assisted↗

Hepatitis C virus replication in 'autoimmune' chronic hepatitis.

Both high and low anti-hepatitis C virus antibody (anti-HCV) prevalence has been reported in autoimmune chronic active hepatitis. Therefore, we studied 15 consecutive HBsAg-negative, ELISA anti-HCV-positive, autoantibody-positive patients with biopsy proven chronic active hepatitis in order to confirm ELISA specificity by immunoblot test (RIBA-HCV), and to evaluate HCV replication by serum HCV-RNA. Nine patients were anti-nuclear, three type 1 anti-liver-kidney microsomal and three anti-smooth muscle antibody positive. None had associated autoimmune disease. All cases showed mild clinical disease and only moderate necroinflammatory activity. Response to prednisone was poor. RIBA-HCV confirmed ELISA results in all patients. HCV-RNA was found in the serum from 10 patients. Institution of alpha-interferon treatment in three steroid non-responsive patients was followed by prompt normalization of transaminases. Thus, a subgroup of autoantibody-positive chronic active hepatitis can be recognized as HCV-related and should be clinically and etiologically distinguished from autoimmune chronic active hepatitis. Trials of alpha-interferon treatment are worthwhile in this condition.

Autoantibodies↗

Is autoimmune chronic active hepatitis a HCV-related disease?

We evaluated the specificity and clinical relevance of anti-hepatitis C virus antibody positivity in 22 HBsAg-negative patients with autoimmune (anti-nuclear, anti-actin or anti-liver-kidney microsomal antibody positive) chronic active hepatitis. An ELISA anti-HCV test and a recombinant immunoblot assay (RIBA-HCV) were used. Thirteen patients (59%) were anti-HCV positive and five (23%) anti-HCV negative by both ELISA and RIBA-HCV tests. Four patients (18%) were borderline positive by ELISA (OD less than 1.0), and three of them (all with severe disease) were negative by RIBA. Histologic necroinflammation, AST/ALT and gamma-globulins levels were higher and response to prednisolone treatment was better in RIBA anti-HCV-negative than in anti-HCV-positive cases. We confirmed with both RIBA and ELISA tests the high prevalence of anti-HCV already reported by ELISA in anti-nuclear and anti-liver-kidney microsomal antibody positive chronic active hepatitis. False positive for anti-HCV (i.e., a positive ELISA test not confirmed by RIBA) occurred only among patients with severe disease. Since RIBA-negative subjects showed the best response to corticosteroid, they might represent the only subset of cases of 'true' autoimmune chronic active hepatitis.

Adrenal Cortex Hormones↗

Hepatitis C virus antibodies in chronic liver diseases of different aetiology.

To define the prevalence of Hepatitis C Virus (HCV) infection in patients with chronic hepatitis or cirrhosis of any aetiology, we tested a group of 372 consecutive subjects with biopsy-proven chronic liver disease (CLD) for anti-HCV antibodies, excluding active drug-addicts and alcoholics. Our results show that in Southern Italy HCV infection is widespread among subjects with cryptogenic chronic liver disease, as well as in liver diseases with features of autoimmunity (71.7% and 66.7% anti-HCV positive, respectively). Anti-HCV is infrequent among non drug-addicted HBsAg positive subjects (4.7%), and bears no relation to hepatitis D superinfection. Subjects with CLD and a history of parenteral exposure are almost always anti-HCV positive (89.2%). Patients with HBV-related CLD and previous drug-addicts are on the average younger than other disease groups, irrespective of their HCV status. Among subjects whose CLD is related to parenteral exposure, cryptogenic or autoimmune no increase in the rate of anti-HCV positivity seems to bear a parallel relationship to age. No known risk factor for parenteral transmission, other than use of blood or blood products and previous drug-addiction, can be clearly related to HCV infection. No trend to familiar clustering of HCV-induced liver disease is apparent. Liver disease severity, as assessed by transaminase levels and liver histology, does not correlate to anti-HCV status.

Adolescent↗

Role of S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis.

Recent studies have established the clinical efficacy of S-adenosyl-L-methionine (SAMe) in the treatment of cholestasis associated with hepatic diseases, pregnancy and the administration of estrogen-containing oral contraceptives. In 4 clinical trials involving a total of 639 patients with cholestasis due to acute or chronic liver disease, SAMe in an intravenous dose of 800 mg/day or an oral regimen of 1.6 g/day for 2 weeks was superior to placebo in relieving the symptom of pruritus and in restoring serum total bilirubin and serum alkaline phosphatase towards normal. The drug is also effective in intrahepatic cholestasis of pregnancy (ICP), with intravenous administration of 800 mg/day for 2 weeks producing a substantial reduction in pruritus and an improvement in abnormal liver function indices. Moreover, SAMe treatment decreases the incidence of premature labour. SAMe appears to be the first safe and effective approach to the treatment of this syndrome, and also protects against the adverse hepatic effects of small doses of estrogen in patients with a history of ICP by normalising liver biochemistry and the oversaturated biliary lipid composition of the gallbladder bile. In animal models, SAMe reverses the pathological liver changes induced by xenobiotics such as taurolithocholate and alpha-naphthyl-isothiocyanate (ANIT) and the antipsychotic chlorpromazine. Several cooperative mechanisms appear to underlie the anticholestatic action of SAMe, the most important being the restoration of normal hepatocyte membrane fluidity and Na+, K+ ATPase activity, through a reversal of the reduction in phospholipid methylation produced by hepatotoxic agents. In addition, SAMe may act by promoting trans-sulphuration pathway reactions and consequently improving the detoxifying capacity of this metabolic system.

1-Naphthylisothiocyanate↗

Hepatitis B vaccination of relatives of hepatitis B virus DNA positive carriers: an experience with plasma-derived vaccine.

We assessed in a western population the efficacy of a plasma-derived hepatitis B vaccine in relatives of highly infectious hepatitis B virus (HBV) carriers. A consecutive group of 103 HbsAg, anti-HBs and anti-HBc negative household relatives of 45 HBV-DNA positive chronic carriers received a 5 micrograms dose of plasma-derived vaccine at 0, 1, 2 and 12 months. Protective levels of immunity developed in 101 subjects (97.8%) 3 months after boosting. Low responders to the vaccine were mostly found among parents and spouses of carriers, whilst offspring and siblings were usually high responders. The main discriminant in predicting a good response was age below 12 years. Hyporesponsiveness did not occur in family clusters. No major HBV events occurred among immunized relatives patients. Hepatitis B vaccine is safe and effective in immunizing relatives of HBV carriers while no genetic conditioning of the immune response is evident among them.

Adult↗

Characterization of the platelet-aggregating activity of cancer cells with different metastatic potential.

We studied the mechanisms of platelet activation by sublines exhibiting different metastatic potential of two murine experimental tumors: sublines M4 and M9 of the benzopyrene-induced mFS6 sarcoma and sublines B77-AA6 and B77-3T3 of RSV-transformed BALB/c 3T3 fibroblasts. The neoplastic cells of both models induced platelet aggregation, secretion and prostaglandin biosynthesis. In the first model but not in the second, all these processes correlated with the in vivo malignancy of cells. Pretreatment of B77-AA6 and B77-3T3 cells with apyrase significantly decreased platelet aggregation, while pretreatment of M4 cells was ineffective. However, pretreatment with trypsin or neuraminidase was effective in reducing platelet aggregation induced by M4 cells, but not that induced by any of the others; furthermore, phospholipase A2 reduced the platelet response by all sublines. Finally, platelet-activating activity was also found in the pellets obtained following centrifugation of culture media. These results suggest that platelets are stimulated by cancer cells through different mechanisms; platelet activation by a sialo-lipo-protein complex of the cellular membrane was found to be characteristic of the model in which the platelet-aggregating activity of neoplastic cells correlated with their in vivo metastatic behavior.

Adenosine Diphosphate↗

Discovering asymptomatic non-precancerous lesions with cervical cytologic mass-screening campaigns: is it a benefit or a cost?

A total of 3357 women (88.1% married, 82.0% parous) were examined at least once in the mass-screening program carried out by the Legnano Hospital Screening Center in Nerviano (a small town near Milan with 15,600 inhabitants) in 1974, 1977 and 1980. Married women with visible portio and adequate smear were 2758: a visibly healthy cervix was found only in 1143 subjects (41.4%). A total of 1516 married women were examined at least in 2 consecutive campaigns: 1279 (84.4%) reported "no gynecologic treatment in the previous 5 years" at the first campaign, and 899 (59.3%) reported "no gynecologic treatment in the previous 3 years" at their second one. Of 350 women with "medical lesions" and 525 with "surgical lesions" recorded at the first visit, 111 (31.7%) and 232 (44.2%) reported, respectively, a "medical treatment" or a "surgical treatment" at the second visit. In women with "medical lesions" at the first visit, at the second visit a healthy cervix was found in 66.2% of the treated women and in 72.6% of the untreated patients. In those with "surgical lesions" a healthy cervix was successively found in 91.6% of treated and in 40.7% of the untreated patients.

Adolescent↗

Activation of platelet prostaglandin biosynthesis pathway during neoplastic cell-induced platelet aggregation.

In a previous study we found a correlation between metastatic potential and platelet aggregating activity in sublines of a benzopyrene-induced murine fibrosarcoma ( mFS6 ); the purpose of the present work was to elucidate the role of thromboxane biosynthesis by platelets and/or by neoplastic cells in the activation of platelets in this system. The cells of the more malignant subline induced higher aggregation and TxB2 production than those of the non metastasizing one. The supernatants of aggregating cell suspensions contained very few TxB2; furthermore, preincubation of platelets with ASA or Apyrase resulted in inhibition of aggregation and TxB2 production, while preincubation of the cells was ineffective; these results suggest the platelet origin of the measured TxB2 and indicate that platelet-derived ADP plays an important role in their activation, while the production of ADP by the cells does not seem to be relevant in this model. The involvement of platelet prostaglandin biosynthesis pathway in neoplastic cell induced platelet activation could play an important role in the development of platelet-dependent tumour metastasis.

Animals↗

Extracellular matrices produced in the presence of dexamethasone: a natural "growth agent" for human cultured endothelium.

Cultured endothelium synthesizes an extracellular matrix that resembles the basement membrane of the vessels. We studied the aspect of extracellular matrices produced in presence or absence of dexamethasone by immunofluorescent technique for fibronectin; the glycoprotein is more abundant in matrices produced in the presence of dexamethasone than controls and forms a very dense meshwork. When endothelial cells resuspended in medium without FCS were seeded on these preformed matrices they adhered and replicated. The endothelium grown on matrices preformed in the presence of steroid showed a better morphology and covered a greater area indicating the presence of more abundant fibronectin content in basal lamina.

Cell Adhesion↗

The effect of ticlopidine on human endothelial cells in culture.

The effect of ticlopidine at various concentrations (150, 30, 6 microM), has been studied on cultured endothelial cells derived from human umbilical cord vein. Ticlopidine affects the initial attachment of endothelial cells to artificial substrata and has an inhibitory effect on endothelial cell growth rate which correlates to the concentration of the chemical in the culture medium. These effects are related to a marked reduction of intra- and extracellular fibronectin as evidentiated by immunofluorescence. The drug seems to interfere with the formation of fibronectin filaments from intracellular granules. The reduction of fibronectin availability could affect platelet adhesion to subendothelium as well as endothelial cell repair, and subsequently influence the bleeding time. The inhibition of cell proliferation and its possible effect on the thickness of the vessel wall should be considered as additional mechanisms of action for this substance.

Anticoagulants↗

Interactions between tumor cells and vascular endothelium.-I) Adhesion properties of cell lines with different metastasizing capacity.

The authors describe the adhesive properties of four murine tumor lines, chemically and virus induced, with different metastasizing potential. Cancer cells show similar behaviour in attachment kinetics when tested with endothelium monolayer or plastic surfaces, without differences between the lines with high or low malignancy. The time required for a complete adhesion to endothelial cells is three hours while to plastic surfaces is 90 min. The role of divalent cations is not required in the first phases of cellular attachment of tumor lines to plastic dishes.

Animals↗

Interactions between tumor cells and vascular endothelium.-II) Light and electron microscopic studies.

Electron microscope technique was used to investigate the passage across the endothelial monolayer by murine tumor lines. After the initial adhesion, cancer cells induce a retraction of endothelium and migrate under vascular intima. Subsequently they spread on basement membrane showing a flattened shape, meanwhile endothelial cells reconstitute the monolayer. The four tumor lines show a similar behaviour being able to induce endothelial retraction and exposure of extracellular matrix and cross through the monolayer. The technique appears useful to study in details this multi-step process.

Animals↗