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Biomedical subjects

M Colombo

Publications and source records attributed to M Colombo.

At least 199 records · Page 11Linked to original sources
PubMed1990

Low risk for hepatitis C in hemophiliacs given a high-purity, pasteurized factor VIII concentrate. International Study Group.

STUDY OBJECTIVE: To assess whether the hepatitis B virus (HBV), the hepatitis C virus (HCV), and the human immunodeficiency virus (HIV) are transmitted to hemophiliacs by a high-purity factor VIII concentrate in which the method of virus inactivation is pasteurization. DESIGN: Hepatitis B virus markers, the antibody to HCV (anti-HCV), the antibody to HIV (anti-HIV), and aminotransferases were measured on serum samples collected before the first concentrate infusion and at regular time intervals thereafter. SETTING: Seventeen hemophilia centers in Italy, the Federal Republic of Germany, Belgium, Austria, and the Democratic Republic of Germany. PATIENTS: Twenty-nine patients with hemophilia A who had not received a previous transfusion with blood products and who had normal alanine and aspartate aminotransferases (ALT and AST) were included in the final analysis. MEASUREMENTS AND MAIN RESULTS: No patient became positive for anti-HCV or anti-HIV or developed sustained increases in aminotransferase levels. Similarly, none of the 15 unvaccinated patients developed markers of HBV infection. CONCLUSION: This prospective study conducted in previously untransfused hemophiliacs highly susceptible to developing post-transfusion hepatitis shows that a large-pool clotting factor concentrate treated with pasteurization carries a low risk for transmitting HCV, the major causative agent of post-transfusion hepatitis.

Adolescent↗
PubMed1990

Serum hepatitis B virus DNA detects cryptic hepatitis B virus infections in multitransfused hemophilic patients.

The recognition of replicating hepatitis B virus (HBV) may be important to both define the cause of and know how to manage chronic liver disease in multitransfused hemophilic patients. Replicating HBV can be detected at the molecular level by methods for HBV-specific DNA (HBV-DNA), which are much more sensitive than the immunologic methods for detecting hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Unselected hemophilic patients (260; 6% with HBsAg, 4% with isolated anti-hepatitis B core (anti-HBc), 52% with anti-HBs and anti-HBc, 26% with isolated anti-HBs, and 12% with no HBV marker) were investigated retrospectively with a dot spot hybridization technique that detects serum HBV-DNA down to 0.5 pg and by Southern blot analysis, which tests the specificity of the HBV-DNA reactions. Eighteen patients (7%; five with serum HBsAg and 13 HBsAg seronegative with antibodies to HBV) had serum HBV-DNA. Serum HBV-DNA was detected more frequently in HBsAg carriers than in seronegative patients (33% versus 6%, P less than .01), and had no relationship to serum alanine aminotransferase. Serum HBV-DNA was more sensitive than the radioimmunoassay for HBeAg was for detecting replicating HBV (7% versus 1.1%, P less than .01). These findings demonstrate that there is cryptic HBV infection in a number of hemophiliacs and that serum HBV-DNA may coexist with markers thought to reflect immunity against HBV.

Adolescent↗
PubMed1990

Auditory association cortex lesions impair auditory short-term memory in monkeys.

Monkeys that were trained to perform auditory and visual short-term memory tasks (delayed matching-to-sample) received lesions of the auditory association cortex in the superior temporal gyrus. Although visual memory was completely unaffected by the lesions, auditory memory was severely impaired. Despite this impairment, all monkeys could discriminate sounds closer in frequency than those used in the auditory memory task. This result suggests that the superior temporal cortex plays a role in auditory processing and retention similar to the role the inferior temporal cortex plays in visual processing and retention.

Animals↗
PubMed1990

MAO activity, metabolism and anticonvulsant activity of milacemide in rats and mice.

Milacemide was found to protect Swiss albino CD1 mice but not Sprague Dawley rats against bicuculline-induced lethality. Since it had been previously suggested that the anticonvulsant activity of milacemide might be related to MAO-B- mediated glycine formation, brain and liver MAO-A and-B activities and the urinary metabolic pattern of milacemide were determined in the same mice and rat strains. Similar brain and liver MAO activities were found in the two species, except for liver MAO-A activity which was higher in rats. After the same oral dose of milacemide, the percent of the dose excreted as glycinamide was significantly higher in mice than in rats, whereas that excreted as metabolite UK1 was significantly higher in rats. These results support the hypothesis of a glycine-mediated anticonvulsant activity for milacemide and suggest that the increased formation of UK1 to the detriment of glycinamide might account for the lack of protection against bicuculline-induced lethality by milacemide in rats.

Acetamides↗
PubMed1990

Does FAD-dependent polyamine oxidase contribute to the metabolism of milacemide?

Milacemide, a secondary amine derivative, was previously demonstrated to be a substrate of MAO-B and to be insensitive to the action of copper-dependent amine oxidases. In the present study, it was investigated whether the FAD-dependent secondary amine metabolizing enzyme polyamine oxidase (PAO), could participate in the metabolism of milacemide. For this purpose, the urinary metabolic pattern of oral 14C-milacemide was determined in rats with and without pretreatment with the irreversible PAO inhibitor MDL 72527 and, for comparison, after inhibition of MAO-B by l-deprenyl. While l-deprenyl was shown to significantly decrease the urinary excretion of glycinamide and of an unknown metabolite (UK1), pretreatment with MDL 72527 did not modify the elimination of milacemide as glycinamide but produced a decrease in UK1 equal to that induced by l-deprenyl. The percent of the dose of milacemide eliminated as unchanged drug was slightly but significantly increased after PAO inhibition, though considerably less than after l-deprenyl. These data suggest that milacemide might be a substrate of PAO. If confirmed, this result would constitute the first example of the involvement of the FAD-dependent PAO in drug metabolism.

Acetamides↗
PubMed1990

Albumin and collagen gene regulation in alcohol- and virus-induced human liver disease.

Common features of chronic alcoholic liver disease are progressive hypoalbuminemia and a spectrum of liver fibrosis. The molecular mechanisms that account for these effects are still the subject of controversy. Therefore, in the present study we evaluated albumin and collagen gene expression in livers of alcohol abusers and patients with virus-induced liver disease. Albumin and pro alpha 1(I) collagen messenger RNA levels were determined in 30 patients who underwent diagnostic liver biopsy. Of 14 alcoholics, 7 had alcoholic hepatitis alone and the other 7 had cirrhosis plus alcoholic hepatitis. Of 16 nonalcoholic patients with chronic viral infection, 6 had chronic active hepatitis and 10 had cirrhosis plus chronic active hepatitis. Total RNA was extracted from a portion of each biopsy specimen, hybridized with a human albumin or collagen complementary DNA clone, and compared with 2 normal surgical specimens, which served as controls. The Northern hybridization studies showed that (a) despite the presence of inflammation and fibrosis, the albumin messenger RNA levels of alcoholics were similar to those of the controls; (b) these alcoholics had significantly higher levels of albumin messenger RNA than did patients with similar histological levels of disease due to viral infection; and (c) all the categories of patients had markedly increased procollagen messenger RNA levels compared with controls. Given these results it is tempting to speculate that alcohol may actually increase albumin messenger RNA content in humans as it does in animals. Furthermore, the increased procollagen messenger RNA levels in fibrotic livers suggest that an increase in collagen syntheses may be a significant factor in the pathogenesis of hepatic fibrosis.

Adult↗
PubMed1990

The (+)-enantiomer is responsible for the antiplatelet and anti-inflammatory activity of (+/-)-indobufen.

The racemic compound indobufen and its (+)- and (-)-enantiomers have been compared for their effects on blood platelet function and rat carrageenan pleurisy. The antiplatelet properties were studied in-vitro in human platelets by measuring the inhibition of platelet aggregation and generation of serum thromboxane (Tx) B2. In-vivo, the antiplatelet and anti-inflammatory properties were studied in rats by measuring the inhibition of serum TxB2, the amount of 6-keto-PGF1 alpha in pleural exudate and pleural exudate volume. In all tests the (+)-enantiomer was slightly more potent than the racemate, while the (-)-enantiomer was far less potent. In the same rats, treatment with the lowest doses of the compounds giving 90% inhibition of serum thromboxane B2 generation was associated with occasional macroscopic lesions of the gastric mucosa.

Animals↗
PubMed1990

Detection of hepatitis B virus DNA in formalin-fixed, paraffin-embedded liver tissue by the polymerase chain reaction.

DNA isolated from formalin-fixed, paraffin-embedded liver tissues from nine patients with hepatocellular carcinoma and six control patients was screened for hepatitis B virus (HBV) DNA with surface (S) and core (C) gene-specific primers by a modification of the polymerase chain reaction--southern blot technique (PCR-SB). PCR-SB results were correlated with histologic, immunohistochemical, and serologic findings. All cases with an established HBV etiology were positive by PCR-SB, as were three cases with negative immunohistochemistry and serology. Often there was selective amplification with one primer set and, in two cases, smaller than expected HBV amplification products suggesting internal deletions. The presence of a potent PCR inhibitor in nucleic acid preparations from tissue blocks that can be removed by Sephadex G-50 chromatography was confirmed. PCR-SB will be a powerful method for the diagnosis and follow-up of patients with HBV infection and may provide new insights into viral hepatocarcinogenesis.

Base Sequence↗
PubMed1989

Prevalence of antibodies to hepatitis C virus in Italian patients with hepatocellular carcinoma.

A sensitive radioimmunoassay was used to detect antibodies to hepatitis C virus (HCV) in patients with hepatocellular carcinoma and chronic hepatitis. HCV antibodies (anti-HCV) were detected in 86 of 132 patients with hepatocellular carcinoma with no relation to the presence or absence of hepatitis B surface antigen (HBsAg). The prevalence of anti-HCV was also high in patients with diseases thought to predispose to hepatocellular carcinoma, such as non-A, non-B chronic hepatitis and cirrhosis (74%). In HBsAg-negative patients with hepatocellular carcinoma the prevalence of anti-HCV was lower than that in patients with non-A, non-B chronic hepatitis (16% vs 55%); the prevalence of serum antibodies to hepatitis B core antigen (anti-HBc), a marker of hepatitis B virus infection, was 70% and 28%, respectively. In HBsAg-negative patients with hepatocellular carcinoma, anti-HCV and anti-HBc occurred together nearly three times as often as in patients with chronic hepatitis (54% vs 19%). These data indicate that, in Italy, HCV is an important factor associated with hepatocellular carcinoma and non-A, non-B chronic hepatitis.

Adult↗
PubMed1989

Distribution of basement membrane components in human hepatocellular carcinoma.

The distribution of fibronectin (FN), laminin (LAM), and collagen IV (Coll IV), three components of the basement membranes (BM), was investigated in human hepatocellular carcinoma (HCC) and the surrounding uninvolved liver and was compared with the grade of differentiation of the tumor. The following three patterns of BM antigens were observed in HCC: (1) peritrabecular or periacinar, (2) pericellular, and (3) stromal-vascular. In the more differentiated tumors, FN, LAM, and Coll IV were observed in a peritrabecular or periacinar pattern whereas a pericellular pattern was only seen with anti-FN antisera that occasionally stained the content of acini. Double staining showed that the four antigens were usually codistributed. Occasionally, however, there was a different distribution along the BM suggesting an heterogeneity in the composition of BM. In the more anaplastic tumors and in the intrahepatic metastasis, BM components were seen around vessels and in the stroma and they were usually fragmented. The finding that FN can be located pericellularly or within acini supports the concept that FN is synthesized, at least in part, by hepatoma cells. The peritrabecular and periacinar location of Coll IV and LAM suggests a sinusoidal cell derivation of these two antigens. The immunohistochemical staining patterns for BM in HCC reflect the differentiation of the tumor, with differentiated tumors showing a relatively intact BM and poorly differentiated tumors showing a sharply defective BM.

Basement Membrane↗
PubMed1989

Beta-blockade prevents recurrent gastrointestinal bleeding in well-compensated patients with alcoholic cirrhosis: a multicenter randomized controlled trial.

To assess the efficacy of beta-blockers in preventing rebleeding in selected cirrhotic patients and to compare the tolerance, safety and patient compliance of a selective and a nonselective beta-blocker, 94 patients were randomly assigned to propranolol (32 patients), atenolol (32 patients) or placebo (30 patients). Randomization was made at least 15 days after the bleeding episode. Propranolol was given orally at increasing doses until the resting pulse rate was reduced by approximately 25%. Atenolol was given at a fixed dose of 100 mg per day. Patients were followed up for a mean of 357 days. Rebleeding occurred in 14 patients in the placebo group, 10 in the atenolol group and eight in the propranolol group. The incidence of rebleeding was significantly lower in patients receiving propranolol than in those on placebo (propranolol vs. placebo: p = 0.01, logrank test). Atenolol was less effective than propranolol (atenolol vs. placebo: p = 0.065, logrank test). Bleeding-free survival was better for patients on active drugs than for those on placebo (propranolol vs. placebo = p = 0.01, atenolol vs. placebo: p = 0.05, logrank test). Retrospective analysis revealed that, whatever the type of treatment, abstinence from alcohol was crucial in preventing rebleeding. We conclude that beta-blocker treatment is effective in preventing rebleeding from esophageal varices in carefully selected alcoholic cirrhotic patients who survive at least 2 weeks after acute variceal hemorrhage and stop drinking.

Actuarial Analysis↗
PubMed1989

Serum type III procollagen peptide and laminin (Lam-P1) detect alcoholic hepatitis in chronic alcohol abusers.

The diagnosis of alcoholic hepatitis is difficult to establish by conventional clinical and laboratory methods, and a firm diagnosis relies on liver histology. Since there are severe limitations in following patients with repeated liver biopsies, noninvasive procedures are needed to assess the presence of alcoholic hepatitis in chronic alcohol abusers. It has been suggested that serum Type III procollagen peptide levels correlates with the degree of inflammation in chronic liver disease. Since inflammation is a major histological finding in alcoholic hepatitis, we therefore studied the usefulness of measuring serum Type III procollagen peptide and laminin values in 45 consecutive chronic alcohol abusers, with or without cirrhosis, in detecting those with alcoholic hepatitis. The results showed that both Type III procollagen peptide and laminin values were elevated in all of the patients with established liver damage. However, the values were highest in those with liver cirrhosis plus alcoholic hepatitis (Type III procollagen peptide 50.4 +/- 36.4 ng per ml vs. 8.1 +/- 2.6 in controls, p less than 0.01; laminin 4.50 +/- 1.49 units per liter vs. 1.24 +/- 0.26 units per liter in controls, p less than 0.01), followed by subjects with alcoholic hepatitis alone (Type III procollagen peptide 23.5 +/- 17.6 ng per ml, p less than 0.01; laminin 2.60 +/- 1.09 units per liter, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Immunogenicity of a yeast-recombinant hepatitis B vaccine in high-risk children.

Horizontal transmission of hepatitis B virus (HBV) from illicit drug users to their contacts, including young children, can be prevented by active immunization against HBV. Yeast-recombinant hepatitis B vaccines are now available for this purpose, but their potential efficacy in such high-risk contacts has not yet been evaluated. Therefore we gave 20 mcg of a recombinant yeast-derived hepatitis B vaccine to 38 children who were at high risk for HBV infection because they had been institutionalized in a community for drug users in which 8.7% of the occupants are carriers. After third dose of vaccine (at 0, 1, and 6 months), all children had anti-HBs responses with titers of 10 mIU/ml or more, with 81% showing responses greater than 1,000 mIU/ml. At 12 months, the percentage of anti-HBs-positive children was 100%, and the percentage of children with anti-HBs higher than 1,000 mIU/ml was 56%. None of the children developed HBV infection during follow-up. Hence the recombinant vaccine was immunogenic, with percentages of seroconversion and anti-HBs titers comparable with those attained in other categories of high-risk children with plasma-derived vaccines.

Adolescent↗