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Biomedical subjects

A Fasoli

Publications and source records attributed to A Fasoli.

At least 37 records · Page 2Linked to original sources
PubMed1999

Can the MEGX test and serum bile acids improve the prognostic ability of Child-Pugh's score in liver cirrhosis?

BACKGROUND: Liver transplantation is nowadays the therapeutic option for end-stage liver disease. Correct disease staging is the main step towards improving the timing of listing for liver transplantation so as to avoid premature or late entry. The need for correct prognostic evaluation is due to the limited number of donors and to the increasing number of patients awaiting transplantation. Our aim was to verify whether Child-Pugh's score might be improved by adding the monoethylglycinexylidide (MEGX) formation test and/or serum bile acid determination. METHODS: We evaluated 182 cirrhotic patients (44 Child-Pugh class A, 97 class B, and 41 class C) of mixed aetiology referring to a tertiary care centre for functional staging of liver disease. These patients were prospectively followed-up for 12-72 months. During this period, 45 patients died, 46 received a transplant, and 91 survived without transplantation. The end-point of analysis was either survival or liver disease-related death at the 6th, 12th, 18th and 24th months of follow-up. The 46 transplanted patients were excluded from the study upon transplantation. RESULTS: In our study, a cut-off for Child-Pugh's score < 8 confirmed its usefulness, especially in short-term prognostic prediction, while mid- and long-term prediction improved by almost 10% by using the combination of a Child- Pugh's score > 8 and an MEGX value < 15 mg/l. Cox's multi-variate regression analysis indicated that MEGX values either with Child-Pugh's score or with prothrombin activity and ascites were independent prognostic variables. CONCLUSIONS: Besides confirming that Child-Pugh's score as the basis of prognostic evaluation of cirrhotic patients, these results suggest that the MEGX test might be a complement to the original score when a patient is being evaluated for a liver transplantation programme.

Adult↗
PubMed1999

Steatosis and bile duct damage in chronic hepatitis C: distribution and relationships in a group of Northern Italian patients.

BACKGROUND/AIMS: Hepatitis C virus (HCV) related disease follows a long, benign course and most affected patients have mild disease. Liver biopsy is mandatory to grade and stage the disease. Characteristic, though non-specific, HCV histological lesions such as bile duct damage and steatosis have been singled out but their association with non-histological parameters has not been completely defined. Our aim was to study the relationships among these histological lesions and clinical, biochemical, functional and virological characteristics in a group of Northern Italian patients with chronic hepatitis. METHODS: We studied 172 patients with HCV-related chronic hepatitis. Patients were divided into groups on the basis of histology including bile duct damage and steatosis. Clinical, biochemical, functional and virological profiles were related to histological findings. RESULTS: Histological grading and staging of disease increased as the age of patients increased. Steatosis was present in 70% of our patients and was related to a higher degree of fibrosis and to decreased functional activity. The prevalence of bile duct damage was 20%. This lesion was present in older patients with higher staging and impaired liver function. Biochemically it was associated with an increase in aspartate aminotransferase, gammaglutamyltranspeptidase, alkaline phosphatase, and total bilirubin. CONCLUSIONS: In the population we studied, HCV chronic hepatitis was predominantly a mild disease. Moreover both steatosis and bile duct damage were also mild. Steatosis was associated with fibrosis and this might influence liver metabolic function. Bile duct lesions were found in older patients with advanced disease showing biochemical evidence ofcholestasis. The molecular role HCV might play in the pathogenesis of these histological features should be addressed in further studies.

Adult↗
PubMed1998

Wilson's disease with concomitant beta thalassaemia and factor V deficiency.

A case of late presentation of Wilson's disease in a female with a thalassaemic trait is reported in whom diagnosis of Factor V deficiency was made. Despite ignoring the disease for years the patient had compensated cirrhosis. She had a dramatic family history of Wilson's disease affecting at least two brothers and two sisters. Moreover, her haematologic problems were not clinically revealed until diagnosis had been made on the basis of suspicions arising from laboratory results. The therapy of choice for hepatolenticular degeneration was not feasible due to the patient's refusal. Zinc salts were, therefore, administered. To our knowledge the association of such rare genetic disorders has not been reported.

Factor V Deficiency↗
PubMed1995

Low Pentasa dosage versus hydrocortisone in the topical treatment of active ulcerative colitis: a randomized, double-blind study.

OBJECTIVES: To compare a low dosage (1 g/day) rectal preparation of 5-aminosalicylic acid in slightly acidic, buffered suspension (Pentasa) with a hydrocortisone 100 mg/day enema (Cortenema). METHODS: Fifty-two patients with mild to moderate distal ulcerative colitis were randomized under double-blind conditions to receive a rectal preparation of either Pentasa (1 g/day) or Cortenema (100 mg/day) for 3 wk. RESULTS: After 3 wk, both types of treatment resulted in statistically significant improvements in clinical and endoscopic activity. No significant difference was observed between the two drugs in any of the parameters considered, although a statistical trend in favor of Pentasa was evident when analysis was limited to clinical activity (p = 0.07). No side effects were reported in either group. CONCLUSIONS: Our experience confirms that short term topical treatment with a low dosage 5-aminosalicylic acid is at least as effective as 100-mg hydrocortisone enemas in treating mild to moderate distal ulcerative colitis and is generally well tolerated.

Administration, Rectal↗
PubMed1993

Effect of three fibrate derivatives and of two HMG-CoA reductase inhibitors on plasma fibrinogen level in patients with primary hypercholesterolemia.

In order to evaluate the effects of hypocholesterolemic drugs on plasma fibrinogen concentration, six groups of subjects with primary hypercholesterolemia have been put on treatment with diet alone or diet plus fenofibrate (100 mg t.i.d.), slow release bezafibrate (400 mg once a day), gemfibrozil (600 mg b.i.d.), simvastatin (20 mg once a day) or pravastatin (20 mg once a day) respectively. After 1 month of therapy, plasma fibrinogen significantly decreased by 9% and 15% in fenofibrate and bezafibrate groups respectively and increased by 19% in gemfibrozil treated patients. After 4 months of therapy the changes were -16% with fenofibrate, -10% with bezafibrate and +20% with gemfibrozil. No significant changes were observed in patients treated with diet alone, simvastatin or pravastatin. The fibrinogen lowering effect of fenofibrate and bezafibrate does not seem to be related to the hypolipidemic activity of the drugs.

Adult↗
PubMed1993

Chlamydia pneumoniae infection in acute exacerbations of COPD.

Chlamydia pneumoniae, strain TWAR, is a frequent causative agent of acute respiratory disease. We assessed the incidence and prevalence of Chlamydia pneumoniae infections in COPD. We studied, from January 1990 to May 1991, 142 out-patients with acute purulent exacerbations of chronic obstructive pulmonary disease (COPD) and 114 healthy control subjects. Oropharyngeal swab specimens were collected at each exacerbation and analysed using a high definition monoclonal indirect fluorescent antibody test for Chlamydia pneumoniae identification. Immunoglobulins G and M (IgG and IgM) fractions of antibodies to Chlamydia pneumoniae were studied by microimmunofluorescence test. Prevalence of specific IgG was 63% in COPD, and 46% in controls (Chi-squared test p = 0.007). Moreover, mean titre of IgG was significantly higher in COPD than in controls. Five patients were positive for specific IgM (> or = = 1:16), and one had a fourfold increase of IgG titre; four of these patients had been treated with ciprofloxacin 1 g.day-1 for 10 days, and two with erythromycin, 3 g.day-1 for 14 days, with remission of signs and symptoms of exacerbation. Chlamydia pneumoniae identification was always negative. Our data suggest that Chlamydia pneumoniae infection is a rather frequent event in COPD, since at least 4% of exacerbations may be associated with it.

Acute Disease↗
PubMed1992

Effects of slow release bezafibrate on the lipid pattern and on blood glucose of type 2 diabetic patients with hyperlipidaemia.

Ninety-eight type 2 diabetic patients with hyperlipidaemia in stable metabolic control with diet alone (41) or diet plus hypoglycaemic agents (57) were divided into two groups: group 1 was put on treatment with slow release bezafibrate 400 mg a day, while group 2 was considered as control. In group 1, after 1 month of bezafibrate, serum triglycerides fell by 47% and cholesterol by 13%. HDL cholesterol showed a non-significant trend toward an increase. Fasting blood glucose significantly decreased by 6%, fructosamine and glycated haemoglobin by 5%. During OGTT, the area under the curve of both serum C-peptide and blood glucose showed a trend toward a decrease after bezafibrate. However, the difference did not reach statistical significance. Thirty-six patients continued the treatment with the drug for 4 months and 23 for 8 months, without further changes of the lipid pattern and glycaemic control. In the control group no significant variation of the lipid levels occurred and diabetic control slightly worsened during the study. Bezafibrate has been proved to be effective in the treatment of hyperlipidaemia in type 2 diabetic patients. The drug seems moreover to improve glycaemic control. The mechanism by which bezafibrate produces this latter effect remains to be elucidated, though an increase of peripheral insulin sensitivity might be suggested.

Aged↗
PubMed1992

Increased expression of endothelin in bronchial epithelial cells of asthmatic patients and effect of corticosteroids.

We have previously demonstrated that human bronchial smooth muscle cells possess specific binding sites for the potent bronchoconstrictive peptide endothelin 1 and that primary cultures of human bronchial epithelial cells constitutively produce an endothelin-like material that binds to smooth muscle cell receptors with a kinetic ability analogous to that shown by the authentic peptide. To evaluate the potential role of airway epithelium-derived endothelin in the pathogenesis of asthma, we have examined here the expression of endothelin in the bronchial epithelial cells of 6 patients with symptomatic asthma and reversible airflow obstruction. The epithelial cells of 5 normal volunteers and 5 patients with chronic bronchitis and airflow obstruction unaffected by bronchodilators were tested as controls. The bronchial epithelial cells of all the asthmatic patients expressed preproendothelin 1 mRNA, as assessed by in situ hybridization, and released high amounts of mature and biologically active endothelin during a 48-h period of incubation (radioimmunoassay). By contrast, the epithelial cells from normal donors did not contain preproendothelin 1 transcripts, and the endothelin-like material in their supernatants was invariably below the detection limit of the assay. Only a few cells from 2 patients with chronic bronchitis expressed preproendothelin mRNA and endothelin immunoreactivity. When hydrocortisone (10(-6)M) was added to the culture medium of asthmatic bronchial epithelial cells for 48 h, the release of immunoreactive endothelin significantly decreased (p < 0.025), but the numbers of cells expressing preproendothelin 1 mRNA did not change to the same extent.

Adrenal Cortex Hormones↗
PubMed1992

Effects of bezafibrate on biosynthesis of cholesterol and on degradation of native and acetylated low-density lipoproteins in incubated human monocytes.

The effects of bezafibrate on 14C-acetate incorporation into non-saponifiable lipids and on degradation of native and acetylated [125I] low-density lipoproteins (LDL) in cultured human monocytes has been evaluated. The presence of bezafibrate in the incubation medium resulted in a decrease of labelled acetate incorporation into non-saponifiable lipids. In parallel with the decrease in sterol synthesis, bezafibrate produced an increase in total and specific degradation of native low-density lipoproteins, whereas the degradation of acetylated low-density lipoproteins was not affected by the drug. These data, though obtained with concentrations of bezafibrate in the incubation medium greater than those encountered in ordinary therapeutic conditions, support the hypothesis that bezafibrate inhibits cholesterol biosynthesis and increases removal of low-density lipoproteins by activating the specific receptor pathway.

Bezafibrate↗
PubMed1991

Time course of IL1 and IL6 synthesis and release in human bronchial epithelial cell cultures exposed to toluene diisocyanate.

We have previously demonstrated that human bronchial epithelial cells release appreciable amounts of interleukin 1 (IL1) and interleukin 6 (IL6) when exposed to toluene diisocyanate (TDI) in vitro. TDI is an inflammatory and asthmogenic stimulus presumed to act at least in part through immunological mechanisms. The epithelial cell-derived IL1 and IL6 can promote T cell activation and proliferation in culture, and if this also happens in vivo they may contribute to the persistence of the inflammatory response of the bronchial mucosa observed in TDI-sensitive asthmatics. In this study, we confirmed the release of biologically active IL1 beta and IL6-like substances from bronchial epithelial cells exposed to isocyanates in vitro, and related the rate and the magnitude of the cytokine secretion with the pattern of IL1 beta and IL6 gene expression and the extent of epithelial cell injury. In the epithelial cell cultures exposed to TDI, there was a parallel, progressive increase in the expression of IL6 mRNA and in the secretion of IL6 protein between 48 hours and 6 days after exposure. By contrast, although increasing amounts of biologically active IL1 beta were detected in the supernatants of TDI-exposed epithelial cells throughout the 6-day period following exposure, augmented levels of IL1 beta mRNA were only evident 6 days after exposure, suggesting that TDI exposure might have initially affected the enzymatic cleavage of the intracellular IL1 beta precursor and the mechanisms which regulate the secretion of mature IL1 beta.

Blotting, Northern↗
PubMed1991

Levels of endothelin in the bronchoalveolar lavage fluid of patients with symptomatic asthma and reversible airflow obstruction.

We have previously demonstrated that human bronchial smooth muscle cells possess a single class of specific binding sites for the potent bronchoconstrictive peptide, endothelin 1, and that human bronchial epithelial cells constitutively release an endothelin-like material in culture, which binds to smooth muscle cell receptors with a kinetic analogous to that observed with the authentic peptide. To evaluate the potential role of endothelin in the pathogenesis of asthma, we examined in this study the release of endothelin in the airways of six patients with asthma, both at the time when they were symptomatic and had reversible airflow obstruction and during the remission phase of the disease induced by treatment. Five normal volunteers and five patients with chronic bronchitis and airflow obstruction unaffected by bronchodilators were tested as control subjects. The release of endothelin in airway mucosa was assessed by RIA with the bronchoalveolar lavage fluid recovered during bronchoscopy. Patients with asthma had increased amounts of immunoreactive endothelin in bronchoalveolar lavage fluid than normal control subjects or subjects with chronic bronchitis (p less than 0.05) in absence of any significant alteration in the levels of circulating peptide. Treatment of patients with asthma with oral corticosteroids and inhaled beta-agonists for 15 days resulted in improvement of airflow obstruction and in more than threefold reduction in the contents of endothelin in lavage fluid. Our findings indicate that the potent bronchoconstrictive substance, endothelin, may contribute to the pathogenesis of airflow obstruction in asthma.

Adult↗
PubMed1991

Cellular and biochemical characteristics of bronchoalveolar lavage fluid in symptomatic nonallergic asthma.

We have undertaken cellular and biochemical examination of bronchoalveolar lavage fluid from nonallergic patients with asthma to determine the nature and degree of inflammatory process in symptomatic asthma. Six patients with asthma (mean methacholine provocative concentration causing a 20% fall in FEV1 was 0.26 mg/ml) and six control subjects underwent fiberoptic bronchoscopy with bronchoalveolar wash. The patients with asthma shed a higher number of epithelial cells into lavage fluid than normal control subjects (p less than 0.05). Their lavage fluid also contained increased numbers of neutrophils (p less than 0.025), eosinophils (p less than 0.025), and basophilic cells (p less than 0.025), and increased proportion of activated T cells (p less than 0.05). The basophilic cells were mast cells, as indicated by positive labeling with the monoclonal antibody MCG35. Biochemical analysis of lavage fluid demonstrated exudation of protein molecules in airways of patients with asthma with increased contents of albumin (p less than 0.05) and fibronectin (p less than 0.05). In the lavage fluid of patients with asthma, there were also increased amounts of interleukin-1-beta (IL-1-beta) (p less than 0.025), interleukin-6 (IL-6) (p less than 0.025), and granulocyte-macrophage, colony-stimulating factor (GM-CSF) (p less than 0.05), as compared with lavage fluid of normal control subjects. Immunocytochemical evaluation of lavage cells demonstrated that IL-1-beta, IL-6, and GM-CSF were mostly produced by nonciliated epithelial cells and/or monocytes. IL-1, IL-6, and GM-CSF can prime granulocytes to respond to other stimuli and can promote T cell activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Human bronchial epithelial cells modulate CD3 and mitogen-induced DNA synthesis in T cells but function poorly as antigen-presenting cells compared to pulmonary macrophages.

This study was undertaken to investigate the ability of bronchial epithelial cells (ECs) to function as accessory cells. Pulmonary monocytes were our reference cells. ECs and pulmonary monocytes were isolated from the bronchial mucosa and pulmonary parenchyma of subjects undergoing lobectomy for standard clinical reasons. Circulating autologous T cells were rigorously depleted of accessory cells to the extent that they lost the capacity to respond to mitogenic lectins alone. ECs restored mitogen-induced DNA synthesis and DNA synthesis triggered by CD3 cross-linking in T cells, as did pulmonary macrophages, and this was unrelated to HLA-DR expression. The ability of promoting T cell proliferation after CD3 cross-linking was, in part, due to the secretory products of ECs, since their supernatants were also effective. Interferon-gamma-treated ECs were capable of presenting antigens to autologous T cells. This was an HLA-DR-restricted phenomenon, but EC efficiency in this system was less than 40% of efficiency demonstrated by pulmonary monocytes. However, ECs greatly upregulated antigen-specific responses supported by pulmonary monocytes.

Antigen-Presenting Cells↗