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Biomedical subjects

F Fiaccadori

Publications and source records attributed to F Fiaccadori.

At least 37 records · Page 2Linked to original sources
PubMed1995

Prognostic value of adenosine deaminase compared to other markers for progression to acquired immunodeficiency syndrome among intravenous drug users.

This study was designed to determine the prognostic value of erythrocyte adenosine deaminase (ADA) as a possible indicator of progression to AIDS, and compare this with other known cellular and serological markers. At the end of a 3-year study, a cohort of 114 human immunodeficiency virus-1 (HIV-1) seropositive intravenous drug users (IVDUs) from the five different Center for Disease Control (CDC) groups was examined in order to estimate the prognostic relevance with respect to the progression to acquired immunodeficiency syndrome (AIDS) of each of the following markers at baseline value: number and percentage of CD4+ T cells, number of CD8+ T cells, CD4+/CD8+ ratio, IgA and beta 2 microglobulin and ADA levels, and the presence of HIV antigens. Moreover, 57 IVDUs belonging to II and III CDC groups were analyzed in a follow-up study at 6-month intervals, in order to evaluate and compare the behavior of each marker over time. The prognostic significance of each marker was assessed by computing the survival distribution and the Cox analysis in a multivariate model providing the set of markers with greatest predictive value. The levels of ADA and the CD4+/CD8+ ratio showed a linear association with disease staging, whereas beta 2 microglobulin and CD4+/CD8+ ratio were the best predictors for AIDS progression. A highly significant increase in ADA and beta 2 microglobulin was observed during follow-up. The results obtained among HIV-positive IVDUs clearly indicate that the erythrocyte ADA may be considered a reliable marker of the development of HIV infection from the intermediate stages of the disease onwards.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1994

Cytotoxic T lymphocyte response to a wild type hepatitis B virus epitope in patients chronically infected by variant viruses carrying substitutions within the epitope.

Mutations that abrogate recognition of a viral epitope by class I-restricted cytotoxic T lymphocyte (CTL) can lead to viral escape if the CTL response against that epitope is crucial for viral clearance. The likelihood of this type of event is low when the CTL response is simultaneously directed against multiple viral epitopes, as has been recently reported for patients with acute self-limited hepatitis B virus (HBV) infection. The CTL response to HBV is usually quite weak, however, during chronic HBV infection, and it is generally acknowledged that this is a major determinant of viral persistence in this disease. If such individuals were to produce a mono- or oligospecific CTL response, however, negative selection of the corresponding mutant viruses might occur. We have recently studied two HLA-A2-positive patients with chronic hepatitis B who, atypically, developed a strong HLA-A2-restricted CTL response against an epitope (FLPSDFFPSV) that contains an HLA-A2-binding motif located between residues 18-27 of the viral nucleocapsid protein, hepatitis B core antigen (HBcAg). These patients failed, however, to respond to any of other HLA-A2-restricted HBV-derived peptides that are generally immunogenic in acutely infected patients who successfully clear the virus. Interestingly, DNA sequence analysis of HBV isolates from these two patients demonstrated alternative residues at position 27 (V --> A and V --> I) and position 21 (S --> N, S --> A, and S --> V) that reduced the HLA and T cell receptor-binding capacities of the variant sequences, respectively. Synthetic peptides containing these alternative sequences were poorly immunogenic compared to the prototype HBc18-27 sequence, and they could not be recognized by CTL clones specific for the prototype peptide. While we do not know if the two patients were originally infected by these variant viruses or if the variants emerged subsequent to infection because of immune selection, the results are most consistent with the latter hypothesis. If this is correct, the data suggest that negative selection of mutant viral genomes might contribute to viral persistence in a subset of patients with chronic HBV infection who express a narrow repertoire of anti-HBV CTL responses.

Acute Disease↗
PubMed1994

Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells.

It has been suggested that mutations within immunodominant cytotoxic T-lymphocyte (CTL) epitopes may be exploited by viruses to evade protective immune responses critical for clearance. Viral escape could originate from passive mechanisms, such as mutations within crucial CTL epitopes, either affecting major histocompatibility complex binding or T-cell antigen receptor (TCR) recognition. Additionally, it has recently been shown that substitutions of TCR contact sites can yield analogue peptides that can still interact with the T-cell receptor but be unable to deliver a full stimulatory signal, thus inducing anergy or acting as an antagonist for the TCR. We report here that hepatitis B virus isolates derived from two chronically infected patients display variant epitopes that act as natural TCR antagonists with the capacity to inhibit the CTL response to the wild-type epitope. During natural infection, TCR antagonist mutations of CTL epitopes could contribute to the development of viral persistence, especially if the antiviral CTL response is monospecific or the epitope is strongly immunodominant.

Amino Acid Sequence↗
PubMed1994

Octreotide versus terlypressin in acute variceal hemorrhage in liver cirrhosis. Emergency control and prevention of early rebleeding.

Sixty patients with endoscopically confirmed active variceal bleeding entered a randomized controlled clinical trial aimed at comparing the efficacy of octreotide vs. terlypressin in the control of acute variceal hemorrhage (period I, 24 h) and in the prevention of early rebleeding (period II, 6 days). Of the sixty 30 received octreotide (period I, 100 micrograms bolus followed by continuous intravenous infusion at 25 micrograms/h; period II, 100 micrograms t.i.d. subcutaneously), and 30 received terlypressin (period I, 2 mg intravenous bolus every 4 h; period II, 2nd day, 2 mg every 6 h; from 3th to 7th days, 1 mg every 6 h). Control of bleeding was achieved in 23 (76.6%) patients receiving octreotide and in 16 (53%) treated with terlypressin (NS); none of these patients suffered rebleeding during treatment. No significant difference in mortality was observed between the two groups during the hospitalization period. Complications due to therapy were lower with octreotide than with terlypressin (P < 0.01). Under the same effectiveness conditions the cost/benefit ratio must be taken into account.

Cost-Benefit Analysis↗
PubMed1994

Hepatitis C virus viremia following clinical resolution of acute hepatitis C.

Clinical resolution of acute hepatitis C occurs in a limited proportion of cases. However, the rate of hepatitis C virus persistence remains unclear. For this purpose, we conducted a serial study of 60 patients with hepatitis C virus infection from the early stage of the disease for 24 to 80 months (average 50 months). Fourteen cases who recovered from acute hepatitis were selected from this group for prospective analysis of the behavior of liver enzymes, anti-HCV antibodies (RIBA II, Ortho Diagnostic System) and hepatitis C virus-RNA in serum and in peripheral blood lympho-mononuclear cells by nested polymerase chain reaction. Primers were derived from the 5'-untranslated region of the hepatitis C virus genome and the amplified products were detected by gel electrophoresis and a DNA enzyme immunoassay. All patients except two showed early recovery from acute hepatitis that occurred within 3 months from clinical onset. Transaminase normalization was always preceded by clearance of serum hepatitis C virus-RNA, which remained negative throughout follow-up. During the resolution phase of the disease a progressive decline in the antibody response was observed in most of the patients. At the end of the study anti-C100 was negative in half the cases, while anti-C33 and anti-C22 became negative or borderline in five cases. Hepatitis C virus-RNA was found in the peripheral blood lympho-mononuclear cells, but not in the serum, of only one of eight patients tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Comparative analysis of torasemide and furosemide in liver cirrhosis.

This review concerns studies of the comparative efficacy and safety of torasemide and furosemide in patients with cirrhosis of the liver complicated by ascites and oedema. The short-term trials reviewed indicated that in patients who had failed to respond with adequate diuresis and loss of body weight and ascites to bed rest, restricted salt and water intake and spironolactone, torasemide had a longer duration of action than furosemide and resulted in a greater urinary excretion of salt and water and greater loss of body weight. Torasemide also had less effect than furosemide on urinary potassium excretion and unlike furosemide did not increase the fractional excretion of magnesium or phosphate or the blood ammonia concentration. Two longer term trials in similar patients with decompensated hepatic cirrhosis confirm the results of the shorter term studies. These studies, albeit each in relatively small numbers of patients, confirm the ability of torasemide to enhance diuresis, free water clearance and fractional excretion of sodium and chloride, resulting in loss of body weight and mobilization of ascites in patients with decompensated hepatic cirrhosis. In these patients, the relatively small increase in urinary excretion of potassium, induced by torasemide without any marked effect on renal function or on the plasma neurohormonal profile, enhances its potential safety.

Clinical Trials as Topic↗
PubMed1994

Rhodococcus equi infection in HIV-positive patients: report of 5 cases and literature overview.

The importance of Rhodococcus equi infection, an uncommon human pathogen that almost exclusively affects immunocompromised hosts, has greatly increased following the advent of acquired immune deficiency syndrome (AIDS) epidemics. Until the present time, 38 cases of R. equi infection have been described in human immunodeficiency virus (HIV)-infected patients; we now report a further five personal cases. R. equi was acquired via respiratory exposure to animals in less than half of the patients, and caused invasive pulmonary infection (91%), bacteraemia and sometimes bloodstream dissemination. R. equi was easily cultured from sputum or blood, but its diagnosis was often difficult due to microbiological and clinical similarities with other pathogens. The persistence of the micro-organism inside macrophages and its high tissular load represent the major limitation to an effective treatment. Several antibiotics are active in vitro, but their efficacy in vivo depends on macrophage uptake and/or bactericidal activity. Treatment should start with at least two intravenous bactericidal antibiotics for 3-4 weeks, and then continue with oral therapy for a period of up to several months with at least two intracellularly active drugs. Surgical resection of the lesions may be beneficial in selected cases.

AIDS-Related Opportunistic Infections↗
PubMed1994

T-cell response to structural and nonstructural hepatitis C virus antigens in persistent and self-limited hepatitis C virus infections.

Twenty-nine patients with chronic hepatitis C and 15 asymptomatic hepatitis C virus antibody-positive subjects who clinically recovered from hepatitis C virus infection were studied for their peripheral blood lymphomononuclear cell proliferative response to hepatitis C virus structural and nonstructural antigens (core, envelope, nonstructural 4 and nonstructural 5) expressed in yeast as superoxide dismutase fusion proteins, in an initial attempt to define some of the features of the virus-specific immune response. Hepatitis C virus core was the most immunogenic antigen for human leukocyte antigen class II-restricted T cells in both groups of patients studied, and the proliferative response to it was the most vigorous and the most frequently expressed in comparison with the other antigens tested. The specificity of the results was supported by the lack of response to hepatitis C virus antigens by healthy uninfected controls and confirmed by recognition of recombinant core proteins of different origin (yeast and baculovirus) by polyclonal T-cell lines produced by T-cell stimulation with yeast-derived core. Each of the antigens tested was able to induce significant although variable levels of proliferative response, indicating that all can be immunogenic at the T-cell level. Significant proliferative responses to core, nonstructural 4 and nonstructural 5 antigens were more frequently detected in subjects who were able to eradicate infection than in patients with chronic hepatitis C, although the difference was statistically not significant. No difference was observed between the two groups of patients with respect to the response to the putative envelope antigens.

Adult↗
PubMed1993

Cell mediated immune response to hepatitis B virus nucleocapsid antigen.

A coordinated and efficient development of humoral and cell-mediated immune responses is believed to be required for complete eradication of viral infections. During the course of hepatitis B virus (HBV) infection, the HLA class II and class I-restricted T cell responses to HBV nucleocapsid antigens are vigorous in patients with acute infection who succeed in clearing the virus but weak or totally absent in patients with chronic persistence of the virus. These findings suggest a role for these responses in the pathogenesis of hepatitis B and in HBV clearance. Molecular analysis of T cell recognition of the HBV nucleoprotein defines the presence of immunodominant core epitopes recognized by helper and cytotoxic T cells that may represent the starting point for the design of alternative strategies for prevention and treatment of HBV infection.

Amino Acid Sequence↗
PubMed1993

Torasemide versus furosemide in cirrhosis: a long-term, double-blind, randomized clinical study.

The effects of long-term therapy (70 days) with torasemide (20 mg/day), a new loop diuretic, were compared with those of furosemide (50 mg/day) in a randomized double-blind trial. Both drugs were administered in association with spironolactone (200 mg/day) in 28 nonazotemic cirrhotic patients with controlled ascites. The treatments did not modify creatinine clearance and exhibited a similar effect on body weight, urinary volume, and fractional excretion of uric acid, sodium, and chloride. The effect of torasemide on fractional potassium excretion was lower than that of furosemide. Torasemide showed higher sparing effect than furosemide on calcium, inorganic phosphate, and magnesium excretion and stronger action on free water clearance. No changes in serum parameters were induced by either treatment. Two episodes of hepatic encephalopathy occurred in the torasemide group. In view of its effects on sodium and water excretion and on other urinary parameters, torasemide can represent an alternative tool for the long-term treatment of ascites.

Ascites↗
PubMed1992

Immune pathogenesis of hepatitis B.

Available information about the immune pathogenesis of HBV infection in man is very limited. However, the present availability of recombinant sources of the different HBV antigens expressed in the appropriate forms to induce activation of either HLA class I or HLA class II-restricted T cells, provides the necessary tools to investigate directly the mechanisms of liver damage, the role of the different cellular components of the immune system in HBV clearance and the specific nature of the immune defects potentially responsible for the chronic evolution of HBV infection. In addition, improved knowledge of HBV biology suggests a dynamic interpretation of the HBV-immune system interactions, based on which viral mutations as well as direct interferences of HBV with specific immune functions are believed to play a relevant role with respect to the outcome of HBV infection.

Hepatitis B↗
PubMed1992

Long-term follow-up of anti-hepatitis C virus antibodies in patients with acute nonA nonB hepatitis and different outcome of liver disease.

We screened 74 patients with nonA nonB acute hepatitis (37 of post-transfusion PTH, and 37 of non-post-transfusion, NPTH, origin) for the presence of anti-HCV by tests detecting either C100-3 antibodies alone (ELISA I) or C100-3 plus C33c plus C22-3 antibodies (ELISA II). Samples were taken at the onset of disease and then serially for a period of time ranging from 12 to 60 months. An increased number of anti-HCV positive cases (86% vs 69%) and an earlier seroconversion were observed with the second compared to the first generation ELISA. Positive samples were confirmed by recombinant immunoblot assay (RIBA), which was also used to study the kinetics of the antibody response to individual HCV antigens. Anti-C33c and anti-C22-3 antibodies were the first detectable markers of HCV infection in 80% and 20% of the patients, respectively. Thirty-two percent of the patients studied showed complete and persistent biochemical recovery, whereas 68% maintained a chronic elevation of the transaminase values. Among the 20 patients who showed early and persistent normalization of the transaminase values, complete disappearance of all antibody reactivities was limited to five of them, whereas in four cases only anti-C100-3 and anti-5-1-1 became negative.

Acute Disease↗
PubMed1992

Hepatitis B virus (HBV)-specific cytotoxic T-cell (CTL) response in humans: characterization of HLA class II-restricted CTLs that recognize endogenously synthesized HBV envelope antigens.

In this study, we show that CD4+, hepatitis B virus (HBV) envelope-specific T-cell clones produced by stimulation with a particulate antigen preparation are able to recognize and kill not only autologous antigen-presenting cells incubated with exogenous HBV envelope antigens but also autologous HLA class II-positive cells expressing endogenously synthesized HBV envelope antigens following infection with recombinant vaccinia viruses or transfection with recombinant Epstein-Barr virus expression vectors. Experiments with lysosomotropic agents and brefeldin A suggest that the endosomal compartment is likely involved in the processing of endogenously synthesized viral proteins for recognition by CD4+ T cells. Our study indicates that HBV envelope-specific, HLA class II-restricted CD4+ cytotoxic T lymphocytes can potentially participate in the immune clearance of HBV-infected cells and the pathogenesis of hepatocellular injury in hepatitis B.

Ammonium Chloride↗