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Biomedical subjects

S Bruno

Publications and source records attributed to S Bruno.

At least 73 records · Page 4Linked to original sources
PubMed1996

Phenotypic, functional and molecular analysis of lymphocytes associated with bladder cancer.

Bladder-washing-derived lymphocytes (BWDL) from 67 patients with bladder cancer were studied. The large majority of samples contained a pure population of T lymphocytes, whereas B and NK cells were absent. A comparative analysis of bladder lymphocytes and peripheral blood lymphocytes (PBL), collected in parallel, showed that BWDL significantly differed from PBL. In vitro cultures of bladder lymphocytes were attempted on 21 samples but in vitro expansion was only possible on six patients treated with bacillus Calmette-Guérin (BCG). This finding indicates that BWDL are characterized by a severe proliferative defect. Nevertheless, the addition of BCG on bladder lymphocytes expanded in vitro enhanced their proliferation, suggesting that this population is sensitized against BCG antigen(s). The analysis of T cell receptor restriction patterns showed that bladder lymphocytes from patients under BCG treatment were oligoclonal. A possible explanation for the efficiency of the immune response and good clinical outcome in patients treated with BCG could be found in the high homology between some BCG antigens and human heat-shock proteins, which are overexpressed in transformed cells.

Adult↗
PubMed1996

Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: a case-control study.

BACKGROUND & AIMS: Viral genotypes have been associated with different severity and outcome of hepatitis C virus (HCV)-related liver disease. The aim of this study was to determine whether HCV genotypes may influence the cirrhosis-related risk of the development of hepatocellular carcinoma (HCC). METHODS: Three groups of patients were studied: 593 patients with chronic hepatitis, 166 patients with HCC and cirrhosis, and 219 patients with cirrhosis but without HCC. A cross-sectional study of frequency distribution and a case-control analysis were performed. HCV genotypes were detected according to Okamoto. RESULTS: HCV type 1b infection was more prevalent among patients with HCC compared with patients with cirrhosis but without HCC (P < 0.01) and chronic hepatitis (P < 0.001). Age, male sex, and HCV type 1b significantly influenced the risk of cancer in cirrhosis by univariate analysis. A pairwise comparison performed on 162 patients with HCC and an equal number of patients with cirrhosis matched by age, sex, and Child's class showed that HCV type 1b was independently associated with HCC (odds ratio, 1.7; P = 0.026). CONCLUSIONS: HCV type 1b is overrepresented in patients with cirrhosis and HCC and significantly influences the risk of HCC in cirrhosis, independent of sex, age, and Child's class.

Adult↗
PubMed1996

Effect of tamoxifen on endometrial proliferation.

PURPOSE: An increase in the incidence of endometrial cancer and a potential increase in related mortality has been associated with the administration of 20 mg tamoxifen, the dose adopted in breast cancer chemoprevention trials, thus urging studies on intermediate markers of risk. PATIENTS AND METHODS: Thirty-three women who received 20 mg tamoxifen as adjuvant breast cancer treatment underwent endometrial biopsy. Samples were divided for histologic examination, including a quantitative analysis of stromal:epithelial ratio, and an assessment of DNA ploidy and proliferation by flow cytometry. Results were compared with 37 symptomatic subjects. RESULTS: All histograms were DNA diploid. Compared with controls, a significant increase in the risk of proliferation as measured by the hyperdiploid fraction was associated with tamoxifen duration (< or = 36 months: cumulative odds ratio = 16.5, 95% confidence interval, 1.85 to 146.5; > 36 months: cumulative odds ratio = 28.2, 95% confidence interval, 2.56 to 310.6, P for trend < .05). Tamoxifen-induced risk was significantly reduced by the extent of menopausal status. No cases of cancer or epithelial hyperplasia were observed in the tamoxifen group, whereas seven cases of epithelial hyperplasia without atypia were observed in the control group. The effect of tamoxifen on proliferation was associated with an increase in the stromal component. CONCLUSION: Tamoxifen at 20 mg/d exerts a time-dependent proliferative effect on the endometrium, particularly in premenopausal and early postmenopausal women. This effect appears to be mediated by the stromal component, which accounts for the discrepancy between flow cytometry and histology. Our study provides preliminary evidence that the DNA flow cytometric hyperdiploid fraction may be a useful tool for monitoring endometrial cell proliferation in women exposed to tamoxifen.

Adult↗
PubMed1995

Expressed cadherin pseudogenes are localized to the critical region of the spinal muscular atrophy gene.

Low-copy repeats have been associated with genomic rearrangements and have been implicated in the generation of mutations in several diseases. Here we characterize a subset of low-copy repeats in the spinal muscular atrophy (SMA) region in human chromosome 5q13. We show that this repeated sequence, named c41-cad, is a highly expressed pseudogene derived from an intact neuronal cadherin gene, Br-cadherin, situated on 5p13-14. Br-cadherin is expressed specifically in the brain, whereas the c41-cad transcripts are 10-15 times more abundant and are present in all tissues examined. We speculate that the c41-cad repeats, separately or in concert with other repeats in the SMA region, are involved in the pathogenesis of SMA by promoting rearrangements and deletions.

Amino Acid Sequence↗
PubMed1995

A simple method for ascites concentration and reinfusion.

A rapid and simple method for ascites concentration and reinfusion was utilized to treat 103 episodes of tense ascites in 57 patients (38 men and 19 women, mean age 63 +/- 11 years). After a bedside total paracentesis, 6.06 +/- 2.87 liters of ascites were separately ultrafiltrated using a mechanical device during a mean interval of 134 +/- 88 min, and 430 +/- 368 ml of concentrate containing 39 +/- 42 g of albumin were restituted at bedside either intravenously (44 cases) or intraperitoneally (59 cases). Ultrafiltration was successfully and easily completed in all cases. Ascites concentration and reinfusion either intravenously or intraperitoneally did not adversely modify hemodynamic or renal parameters except for a transient decrease in mean arterial pressure (P < 0.05). Transitory hyponatremia and renal failure occurred in two patients. A transient decrease in platelet count and serum fibrinogen levels (P < 0.05) and pyrexia (12%) were observed only in patients reinfused intravenously. In conclusion, this new method for ascites concentration and reinfusion was effective, safe, and, with respect to traditional methods, simpler, faster and more comfortable. Therefore it is proposed for the routine management of tense ascites.

Albumins↗
PubMed1995

Liver cell dysplasia is a major risk factor for hepatocellular carcinoma in cirrhosis: a prospective study.

BACKGROUND/AIMS: In humans, the role of liver cell dysplasia as a preneoplastic lesion is still debated. A prospective, long-term, multicenter study was performed to establish whether liver cell dysplasia in cirrhosis is associated with an increased risk for hepatocellular carcinoma (HCC). METHODS: A cohort of 307 consecutive patients in whom liver cirrhosis was diagnosed by histology was investigated for development of HCC at 6-month intervals by ultrasonography and determination of alpha-fetoprotein levels. RESULTS: At enrollment, liver cell dysplasia was found in 75 patients (24%) and in 53% (P < 0.01) of those positive for hepatitis B surface antigen (HBsAg). After a mean follow-up of 46 months, HCC was detected in 45 cases, and it was significantly more frequent in patients with liver cell dysplasia (P < 0.01) and HBsAg-serum positivity (P < 0.01). Multivariate analysis showed that liver cell dysplasia was the most important risk factor correlated with HCC development. HBsAg positivity and age over 60 years were also independent risk factors for HCC. CONCLUSIONS: These results indicate that liver cell dysplasia is a major risk factor for HCC, and it should be looked for carefully by pathologists in liver biopsy specimens to identify patients requiring more intensive observation.

Aged↗
PubMed1995

Molecular epidemiology of hepatitis C virus infection among intravenous drug users.

BACKGROUND/AIMS: The clinico-pathological features of hepatitis C virus infection in intravenous drug users are different from those found in other hepatitis C virus-infected patients. Our aim was to test whether specific viral variants circulate within this particular patient population. METHODS: We studied the distribution of hepatitis C virus genotypes in 90 drug addicts and 484 controls, according to the method described by Okamoto. RESULTS: Hepatitis C virus type 1a and 3a infections were more frequent among intravenous drug users than in 125 age-matched controls (48.8% and 21.1% vs 17.6% and 11.2%), accounting for the majority of infections in intravenous drug users. Analysis of hepatitis C virus genotypes according to age showed that, in the general population, hepatitis C virus types 1a and 3a were more prevalent among patients younger than 40 years of age than in older individuals (17.6% and 11.2% vs 1.4% and 0.6%). CONCLUSIONS: These findings suggest that hepatitis C virus types 1a and 3a were recently introduced in Italy, presumably via needle-sharing among intravenous drug users, and from this reservoir they are extending to the general population, particularly among younger subjects.

Adolescent↗
PubMed1995

Phase II trial of weekly i.v. vinorelbine as a single agent in first-line advanced breast cancer chemotherapy. The Latin-American experience.

This study investigated the therapeutic effect of single-agent i.v. weekly Navelbine (vinorelbine), a semisynthetic vinca alkaloid, in women who had received no prior treatment for locally advanced or metastatic breast cancer. Of 68 patients entered into the study, 63 were adequate inclusions, assessable for toxicity and response by WHO criteria; the 5 patients who were not evaluated were excluded from analysis because they were found not to meet the eligibility criteria of the study. Navelbine was given as a weekly 30 mg/m2 short i.v. (20 minutes) infusion; treatment was continued until disease progression. The overall response rate was 44% (complete response 8%, partial response 36%). The response rate according to target was lymph nodes, 62.9%; liver, 50.0%; lung, 50.0%; skin, 37.5%; and primary tumor, 30.8%. The median duration of response was 17.9 weeks (range: 7-52 weeks). The median time to treatment failure was 12.9 weeks, and the median survival was 50.3 weeks. The 63 eligible patients received 501 cycles. The mean dose intensity was 76%. At least one episode of WHO grade 3/4 granulocytopenia was seen in 46% of the patients (13.6% of cycles). Significant nausea/vomiting was seen in only 5% of patients corresponding to 1% of cycles. Only 5% of patients developed WHO grade 3-4 constipation and grade 3 peripheral neuropathy was observed in 1.6% of patients. Alopecia was rare (6.3% of patients), and other side effects were uncommon. This study confirms that Navelbine has major single-agent antitumor activity as frontline therapy in advanced breast cancer. Given its excellent tolerance profile and low morbidity, it should be recommended for inclusion in first-line combination chemotherapy regimens.

Adult↗
PubMed1995

Differential distribution of hepatitis C virus genotypes in patients with and without liver function abnormalities.

Hepatitis C virus (HCV) infection persists for an indefinite length of time in a major proportion of patients, inducing chronic liver lesions that evolve to cirrhosis and hepatocellular carcinoma (HCC) in approximately 20% of cases. We studied HCV viremia and genotypes by reverse transcription-polymerase chain reaction (RT-PCR) in 341 consecutive anti-HCV-positive patients. Of these, 167 patients had persistently normal or near normal alanine aminotransferase (ALT) levels (fluctuations < or = 5 IU above the upper limit of normal); the remaining 174 patients presented with elevated ALT and histological evidence of chronic liver disease. Seventy percent of patients with normal ALT values had circulating HCV RNA despite the absence of biochemical indicators of liver damage and mild histological forms of chronic hepatitis were detected in most patients who underwent liver biopsy. Isolated genotype III infection was significantly more prevalent in this patient group with respect to control patients with abnormal ALT values (70% vs. 39%; P < .001). Conversely, isolated genotype II was more frequently found in patients with elevated ALT values and evidence of chronic liver disease (45% vs. 23%; P < .01) and it was progressively more represented in advanced liver disease, such as cirrhosis and HCC. Virological features of HCV infection might be associated with different clinical manifestations, suggesting a potential prognostic significance on disease outcome.

Adolescent↗
PubMed1995

In vitro synergism between 5-fluorouracil and natural beta interferon in human colon carcinoma cells.

The combination of 5-fluorouracil (FUra) plus IFN-beta was studied in vitro using a human colon carcinoma cell line, HCT-8. Continuous exposure to high concentrations of IFN-beta is cytotoxic to these cells (ED50, 600 +/- 50 IU/ml). A strong synergism (P < 0.002) was observed when a short-term (1-h), high-concentration exposure to fluoropyrimidine (300 or 1000 microM) was followed by IFN-beta given continuously. In fact, the mean ratio between the expected (product of the survival of each agent alone) and the observed clonogenic cell survival rates of the combination was 3.4 (range, 2.4-4.9). Longer exposures to the fluoropyrimidine (24 h, 7 days) produced less than additive effects with IFN-beta, indicating strong schedule dependency for this synergism. The mechanism of interaction was studied at four levels. First, thymidylate synthase (TS) activity, inhibition, and recovery were measured by an in situ assay in cells treated with FUra, IFN-beta, and their combination. When the prolonged infusion of IFN-beta followed a 1-h exposure to FUra, the observed TS inhibition and recovery, at each time point, were very similar to the expected values, indicating that the interactions between these drugs at the level of TS are not the determinant of the synergism. Second, cell cycle analysis was done. During the continuous exposure to IFN-beta, a significant accumulation of HCT-8 cells in S-phase was observed at 24, 48, and 72 h compared to untreated controls (P = 0.003); however, under the same experimental conditions producing synergy in the clonogenic assay, no significant cell cycle perturbations were produced by the combination of FUra followed by IFN-beta compared to those caused by each agent alone. Third, using the alkaline elution test, we also demonstrated that the synergism is not due to enhanced FUra-induced DNA single-strand break frequency in high molecular weight DNA. Finally, nucleic acid incorporation experiments, using tritiated FUra, showed that the cytokine, given continuously (300 IU/ml), enhanced the amount of FUra incorporated into nucleic acids 24 h after a 1-h exposure to 300 and 1000 microM of FUra. The median percentage of enhancement values were 31.6 +/- 11.5%,m for the lower drug concentration and 18. 4 +/- 8.1% for the higher drug concentration tested. These results suggest that the mechanism of this synergism may be related to the ability of IFN-beta to promote the incorporation of intracellular FUra metabolites into nucleic acids and/or to inhibit the cleavage of FUra nucleotides from RNA/DNA.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Properties of hepatitis B virus pre-S1 deletion mutants.

Deletion mutants of hepatitis B virus (HBV) pre-S proteins were detected in serum in 2 of 10 (20%) individuals with chronic hepatitis B infection following the initiation of interferon treatment. The size of these deletions was up to one-half of the entire pre-S1 region. In vivo, all HBV deletion mutants were found to coexist with a full-length "wild-type" viral genome. The functional properties of a HBV-deleted mutant were studied in detail and revealed a stop codon in the pre-S2 open reading frame in all 20 of the clones sequenced. Several of the deleted mutants produced low-level HBsAg in culture supernatants compared to wild-type virus due to a putative loss of transcription factor binding sites. Transfection experiments in human hepatoma cells (HuH-7) demonstrated that the polymerase gene function was not affected by the large pre-S1 deletions and mutant viral genomes were capable of replication. However, secretion of incapsidated mutant viral genomes was blocked in HuH-7 cells. Cotransfection studies with a plasmid expressing only the HBV pre-S1, pre-S2, and S proteins resulted in complete restoration of viral particle secretion. Our findings suggest that an in vivo trans-complementation phenomenon would have had to occur to permit secretion from the liver into serum of the nucleocapsids containing these deleted viral genomes.

Base Sequence↗
PubMed1994

The evaluation of fine-needle procedures for the diagnosis of focal liver lesions in cirrhosis.

To evaluate the diagnostic accuracy of fine-needle aspiration, fine-needle biopsy and extranodular fine needle biopsy in identifying focal lesions in cirrhosis, 100 consecutive ultrasound detected nodules were studied. Seventy-three were hepatocellular carcinomas (31 were well-differentiated hepatocellular carcinomas), 23 were benign lesions (one angioma and 22 large regenerative nodules) and two were metastases. The lesions were divided according to maximum diameter as follows: < 20 mm in 36, > 20 < 30 mm in 27, and > 30 mm in 33. In four cases there were multiple nodules of different sizes. Fine needle aspiration, intranodular fine needle biopsy and extranodular fine needle biopsy were obtained in each lesion. The sensitivity, specificity and diagnostic accuracy of each procedure were evaluated separately by three independent pathologists. Seven fine needle aspirations and three intranodular fine needle biopsies were considered inadequate. The highest diagnostic accuracy (96%) was obtained by the combined analysis of fine needle aspiration plus intranodular and extranodular fine needle biopsy, and this superiority was confirmed in each group of lesions. Fine needle aspiration showed a lower accuracy (48%) than intranodular fine needle biopsy (67%). When fine needle aspiration and intranodular fine needle biopsy were evaluated together, an accuracy of 91% was found. Intralesional fine needle biopsy plus extranodular fine needle biopsy analysis gave an accuracy of 78% and, particularly relevant, a specificity of 95%. These results indicate that, in patients with cirrhosis with nodular lesions < 30 mm, fine needle biopsy is superior to fine needle aspiration and that the combined evaluation of fine needle aspiration plus intranodular and extranodular fine needle biopsy is the most accurate approach.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy, Needle↗