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Biomedical subjects

O Schiraldi

Publications and source records attributed to O Schiraldi.

At least 37 records · Page 2Linked to original sources

[Enterococcal endocarditis: clinical features and therapeutic approach].

Enterococci are implicated in about 20% of cases of infective endocarditis, topically in aged subjects with gastro-intestinal and/or genitourinary diseases. These forms are usually associated with an increased morbidity and mortality, in that also reflecting the difficulties encountered to set up a specific therapeutic approach. Among the various antibiotics effective against enterococci, particular attention has been recently given to those belonging to glycopeptide group. In the current study we have assessed the efficacy of teicoplanin associated to ampicillin plus sulbactam in 27 consecutive patients with enterococcus-mediated endocarditis, admitted to our hospital between June 1987 and September 1995. In 17 patients the source of infection has been identified in the gastrointestinal tract. The clinical recovery and the bacteriologic eradication have been achieved in 24/27 (88.8%) patients. The results indicate the necessity of a prophylactic antibiotic treatment in aged individuals with diseases affecting the gastrointestinal tract and further suggest the efficacy of teicoplanin and ampicillin plus sulbactam association for the treatment of endocarditis caused by enterococci.

Adolescent↗

CD45RA and CD45RO isoform expression on intrahepatic T-lymphocytes in chronic hepatitis C.

A liver tissue recruitment of antigen-specific cytotoxic cells has been reported in chronic hepatitis C virus (HCV) infection, but whether they really play a role in viral clearance is still a matter of investigation. To further evaluate T-cell involvement in HCV-induced hepatic disease, the authors analysed, in a cohort of chronic hepatitis C patients, the intrahepatic T-cell expression of CD45 isoforms by using specific monoclonal antibodies. Within hepatic specimens, CD45RA+ (naive) cell frequency at the portal tract level was significantly higher than that exhibited at lobular level. At the same time, a large number of CD45RO+ (memory) cells was found at periportal sites in comparison with the lobular counterpart. The evaluation of CD45RA and CD45RO isoform topographical distribution in relation to CD4+ and CD8+ lymphocytes, as determined on serial sections, showed that CD45RA antigen expression was predominantly coexpressed with CD4+ lymphocytes at the portal tract level, and the CD45RO phenotype with CD8 structure at the lobular and periportal sites. The levels of CD45 isoforms did not show any correlation with biological and/or histological disease activities. The results suggest that a liver recruitment of both naive and memory cells occurs during chronic HCV infection, even if their functional role needs to be further clarified.

Adolescent↗

Liver steatosis and chronic hepatitis C: a spurious association?

OBJECTIVE: Based on the observation of steatosis in the majority of liver biopsy specimens from hepatitis C virus (HCV) infected patients, it has been suggested that HCV may be pathogenetically implicated. We aimed to determine the influence of possible underlying metabolic disorders on this association. DESIGN: In a series of 148 consecutive patients with chronic hepatitis, with and without HCV infection, we evaluated by logistic regression analysis the association between steatosis and HCV, controlling for diabetes, obesity, hyperlipidaemia and alcohol. These are all known to be factors associated with a fatty liver, and also with the histological degree of liver disease. RESULTS: Antibodies to HCV were detected in 121 of 148 (81.8%) patients. Steatosis, distributed in different histological patterns, was found in 73 of 121 (60%) HCV-positive and in 14 of 27 (52%) HCV-negative patients (P = NS). Using simple logistic regression, the association Of HCV to steatosis was weak and not statistically significant (OR, 1.14; 95% CI, 0.61-3.27). The same was true for hyperlipidaemia (OR, 4.45; 95% CI, 0.52-37.9). A strong and statistically significant association was found, however, between obesity and steatosis (OR, 4.18) and between steatosis and the highest degree of histological severity (Liver cirrhosis vs chronic persistent hepatitis: OR, 12.8). Using multivariate analysis, the association between steatosis and HCV was shown to be not significant. Hyperlipidaemia, among all the independent variables tested, was shown to be co-linear with obesity. CONCLUSION: Our findings seem to suggest that HCV is irrelevant as a risk factor for a fatty liver. The results indicated that there is a 'confounding' role of obesity and hyperlipidaemia, and that the severity of liver disease is associated with steatosis and HCV.

Adolescent↗

Effects of interferon-alpha treatment on neutrophil oxidative metabolism, lymphocyte proliferation and monocyte HLA class I antigen expression in patients with chronic hepatitis C.

Polymorphonuclear cell (PMN) oxidative metabolism, lymphocyte polyclonal proliferation and monocyte HLA class I antigen expression were evaluated at different intervals of time in patients with chronic hepatitis C (CH-C) subjected to a 6 month interferon alpha (IFN-alpha) treatment and divided into Responder ('R') and Nonresponder ('NR') subsets according to clinical outcome. Before therapy, all subjects exhibited multiple immune alterations even if to a different extent between 'R' and 'NR' subsets: an elevated superoxide anion (O2-) generation by suspended PMN, a failure to further increase neutrophil oxidative responsiveness under adherence conditions, an augmented phytohaemagglutin-induced lymphocyte proliferative capacity and an enhanced HLA class I antigen expression on CD14+ cells. IFN-alpha administration gave rise to a modulation of oxidative response in 'R' group only, since these individuals displayed an O2- release by suspended and adherent PMN which fell within normal values. At the same time, a decrease of lymphocyte proliferation occurred in both groups of patients during IFN-alpha therapy, even if it reached statistical significance in 'R' group only. Finally, a more marked difference between 'R' and 'NR' individuals was noted in terms of HLA class I antigen induction on CD14+ cells at the end of therapy, as a consequence of a reduced expression of these structures in 'NR' subjects. Altogether, these findings suggest the occurrence of a strict relationship between immunoresponsiveness and IFN-alpha induced therapeutical effects in CH-C patients.

Adult↗

Altered expression of basement membrane proteins and their integrin receptors in lichen planus: possible pathogenetic role of gelatinases A and B.

Lichenoid lesions of the skin are characterized by a band-like dermal inflammatory infiltrate and structural alterations of the basement membrane (BM). The etiopathogenesis of these lesions, of which lichen planus (LP) is perhaps the prototypic example, is unknown. Acute cases of LP are accompanied by the destruction of epidermal BM, degeneration of basal keratinocytes with loss of tonofilaments and hemidesmosomes, vesicular alterations, and even blister formation. Chronic LP is characterized by hyperkeratosis and acanthosis in the epidermis, fibrosis, and dense infiltrate in dermis. We found that acute LP lesions are characterized by uneven or absent immunostaining for laminin-5, laminin-1, and collagen type IV. Distribution and activity of gelatinases matrix metalloproteinase (MMP)-9 and MMP-2, and a specific inhibitor of MMP-2, tissue inhibitor of metalloprotein-2, were analyzed. The expression and activity of MMP-2 were increased, whereas tissue inhibitor of metalloprotein-2 expression was weak in the involved areas during the acute phase of LP. Moreover, we demonstrated in vitro that MMP-2 is directly capable of digesting laminin-5 gamma 2 chains to yield a 80-kd fragment. We also observed a weak or absent staining of all examined integrin receptors in the acute LP lesions. In chronic lesions, the staining of BM components was similar to normal controls. In these sections, normal expression of gelatinases and inhibitor was observed. There was, however, up-regulation and altered polarity of integrin receptors. These results indicate a link between overexpression of gelatinases, BM disruption, and altered integrin expression. In LP, the digestion of BM by MMP-2 may contribute to the pathogenesis by inducing altered integrin expression in basal keratinocytes and ultimately blister formation.

Adolescent↗

Hepatitis C virus infection. Biological and immunological features.

The recent cloning and genomic identification of hepatitis C virus (HCV) by sensitive and specific immune techniques has allowed a better definition of both histopathological and clinical features of the previously not well defined non-A, non-B hepatitis. In this regard, antibodies to different HCV antigens are usually found during infection, even if some of them such as anti-E1 and anti-E2/NS1 have been shown to be associated with significant viraemic levels. Acute hepatitis C is self-limiting in a minority of cases only. Over 60% of acute hepatitis becomes in fact chronic and may progress towards cirrhosis. In about 10% of cases, hepatocellular carcinoma may develop in cirrhotic livers. The occurrence of a strict relationship between immunoresponsiveness and disease activity is suggested by the observation that peripheral blood mononuclear cell (PBMC) proliferation induced by NS3 structure is associated with self-limiting acute hepatitis, while PBMC stimulation by core antigen characterizes chronic C hepatitis. The demonstration of lymphoid aggregates, bile duct lesions, intraportal lymphocyte infiltration, increased adhesion molecule expression and augmented cytokine release clearly emphasizes the involvement of immune-mediated reactions in the development of liver damage, even if a direct cytopathic effect cannot be excluded. Finally, it is likely that HCV may favour, through immune-mediated mechanisms, autoantibody generation and/or the appearance of some extrahepatic autoimmune manifestations during the course of HCV chronic infection.

Animals↗

Topical thymopentin therapy in HIV positive patients with recurrent oral candidiasis: a pilot study.

Oral candidiasis frequently occurs in HIV-positive patients especially in those with advanced disease. To date, common anti-mycotic drugs are unable to prevent relapses and alternative therapy is necessary to reduce disabling effects. With the aim of verifying whether thymic hormone extract may be efficacious in these subjects, we enrolled 10 HIV-positive patients with recurrent and/or persistent oral candidiasis to be treated with thymopentin (oral inhalations). All patients benefited from the topical use of thymopentin, and in all cases there was marked increase in salivary secretory IgA which possibly accounted for the candidiasis improvement.

AIDS-Related Opportunistic Infections↗

[Cutaneous vasculitis, mixed cryoglobulinemia in a patient with non-secreting monolateral pheochromocytoma. A likely paraneoplastic syndrome].

We describe a patient who presented with purpuric lesions over his legs, asthenia and arthralgias. The patient was diagnosed as having cryoglobulinemia and no secreting monolateral pheochromocytoma. Two months after the removal of the tumour, the vasculitic lesions disappeared but the cryoglobulins were still present in the patient's serum. The cryoglobulins, which varied from 30 mg/dl to 60 mg/dl, persisted even during the following year. We consider this case noteworthy because the association among leukocytoclastic vasculitis, cryoglobulinemia and no secreting monolateral pheochromocytoma has not been previously described.

Adrenal Gland Neoplasms↗

Psoriatic lesions in patients with chronic liver disease are distinct from psoriasis vulgaris lesions, as judged on basis of integrin adhesion receptors.

Psoriatic lesions are relatively frequent in patients with chronic liver disease. Furthermore, therapy with interferons tends to exacerbate the symptoms. The pathogenesis of psoriatic lesions is unclear. An important question is whether such lesions may be linked to the underlying chronic liver disease in these patients, or whether they are incidental manifestations of psoriasis vulgaris. We collected biopsy specimens from involved and uninvolved skin areas of chronic liver disease patients with psoriatic manifestations, as well as from psoriasis vulgaris patients, and investigated the patterns of integrin adhesion receptors by means of immunohistochemical methods. Integrin expression is known to be characteristically altered in psoriasis vulgaris. We found some of these changes in chronic liver disease psoriatic lesions-namely pericellular redistribution and suprabasal expression of the basement membrane receptor alpha 6 beta 4 and of the intercellular integrins alpha 2 beta 1 and alpha 3 beta 1. However, psoriasis vulgaris causes two other typical changes: One is the induction of the prototype fibronectin receptor alpha 5 beta 1, and the other is the alteration of integrin expression in areas of the epidermis that are macroscopically normal. These two changes were not found in chronic liver disease psoriasis biopsy specimens in 14 patients investigated. Thus integrin expression may be useful in differentiating chronic liver disease psoriatic lesions from psoriasis vulgaris lesions. Even though the two types of lesions are indistinguishable on inspection or by their histological features, they may be caused by distinct pathogenetic mechanisms. It remains to be seen whether the underlying chronic liver disease has a role, albeit indirect, in such mechanisms.

Aged↗

Biological and clinical significance of neutralizing and binding antibodies to interferon-alpha (IFN-alpha) during therapy for chronic hepatitis C.

It is known that IFN therapy can induce the development of anti-IFN antibodies. In order to evaluate the biological and clinical significance of both neutralizing (NA) and non-neutralizing (binding) antibodies, 123 patients with chronic hepatitis C treated with recombinant IFN-alpha were examined. Among them, 15 were positive for NA and 24 for binding antibodies. The kinetics of NA appearance show that, in general, they develop early during the first 3 months of treatment. Moreover, NA seem to be clinically relevant, since they may be responsible for non-responsiveness to treatment in 53% of patients who develop them. The evaluation of the clinical significance of binding antibodies is more difficult. They appear significantly earlier in non-responders than in responders, but no differences were observed in the overall percentage of seroconversion between responders and non-responders. Thus, it is not possible at the moment to establish their possible role in inducing non-responsiveness.

Alanine Transaminase↗

Monoclonal expansion of immunoglobulin not-secreting CD5+ CD11c+ CD38+ B-cells in a rare case of chronic lymphoplasmacytoid leukaemia.

We present the clinical and immunological features of a rare case of chronic lymphoid leukaemia with lymphoplasmacytoid morphology. The patient was first admitted suffering from weakness, pallor, dyspnoea, marked splenomegaly, hepatomegaly and systemic lymphadenopathy and panhypogammaglobulinaemia. White blood cell count revealed important leukocytosis (220 x 10(9) WBC/l) with 2% neutrophils and 98% lymphoid cells showing lymphoplasmacytoid features, while lymphoid cells of identical morphology severely infiltrated the bone marrow and lymph nodes. The disease, initially controlled by non aggressive chemotherapy over a period of 30 months, later evolved to a clinical and haematological picture suggestive of Richter's syndrome. Immunophenotyping of the leukaemic cells demonstrated a monoclonal expansion of B-cells bearing surface markers of typical CLL (CD5, CD19, CD20, CD21, CD22, CD23, CD24, CD40 and low density IgM+IgD/kappa) and also the CD11c and CD38 antigens. A proportion of these cells expressed activation markers (CD25, CD69 and CD71). Following in vitro activation with TPA or PWM, the cells responded by weak incorporation of 3H-TdR but failed to secrete immunoglobulins. These findings confirm the broad morphological, phenotypical and clinical spectrum of chronic lymphoid leukaemias.

Antibodies, Monoclonal↗

Prevalence of antibodies to hepatitis C virus among family members of patients with chronic hepatitis C.

In this study, 108 family members of 40 chronically HCV-infected patients (19 post-transfusion and 21 sporadic), and 45 families of 16 anti-HCV-negative index cases (control group) were tested for anti-HCV antibodies. Anti-HCV antibodies were found in 16 (14.8%) families of anti-HCV-positive index cases (15% males and 14.6% females; p = NS), with no difference between families of index cases with post-transfusion and those with sporadic HCV infection. Out of the 16 anti-HCV positive family members, 12 (75%) had clinical and/or serological evidence of chronic liver damage. None of the control group subjects were anti-HCV-positive (p < 0.01). The rate of anti-HCV positivity was 34.4% among spouses, 14.3% among siblings, 16.7% among cohabitants and 2.3% among children; anti-HCV antibodies were not detected among parents. We found a positive correlation between the prevalence of anti-HCV antibodies among families and the severity of the HCV-related chronic liver damage of the index cases (p < 0.00005). In addition, to confirm that HCV infection and HCV-related chronic hepatitis may be transmitted intrafamiliarly, our findings also indicate that horizontal, especially sexual contact, is a more important route of HCV infection than vertical/perinatal transmission. Finally, the risk of acquiring HCV infection among families appears to be the highest when index cases are suffering from severe HCV-related chronic hepatitis.

Adolescent↗

2',5'-Oligoadenylate synthetase activity as a responsive marker during interferon therapy for chronic hepatitis C.

The 2',5'-oligoadenylate (2-5A) synthetase is an intracellular enzyme induced by interferon (IFN). We evaluated the serum level of this enzyme in 25 patients affected by chronic hepatitis C and treated with recombinant IFN-alpha 2b. At the end of treatment, 14 patients were classified as responders and 11 as nonresponders. Before therapy initiation no significant differences in 2-5A synthetase levels among the patients were detected, while during therapy responders showed higher mean levels of 2-5A synthetase than nonresponders. An increase in the enzyme activity was observed after 1 month of therapy, and this trend was maintained in the following 2 months. The peak of 2-5A synthetase activity was found at the end of therapy. 2-5A synthetase levels were negatively correlated with serum alanine aminotransferase (ALT). This study suggests that 2-5A synthetase may be a useful marker to monitor IFN efficacy during treatment and to predict the clinical response.

2',5'-Oligoadenylate Synthetase↗

Occurrence of hepatitis delta virus infection in hepatitis B virus-infected patients with different serum patterns of preS gene-encoded proteins.

The occurrence of delta superinfection among viremic and nonviremic HbsAg-positive carriers with different serum patterns and levels of preS1 and preS2 antigens was investigated. PreS1 and preS2 antigens in serum, as well as their levels, were found to be independent of hepatitis B virus (HBV) replicative activity. Serological evidence of hepatitis delta virus (HDV) superinfection was found in 34 out of 233 (14.6%) HBsAg-positive carriers; all these 34 patients resulted positive for antibody to hepatitis B 'e' antigen, and 33 of them were negative for circulating HBV-DNA. Delta superinfection occurred only among HBsAg-positive carriers whose sera were reactive for both preS1 and preS2 antigens (30 out of 142; 21.1%) or at least for preS1 alone (4 out of 63; 6.3%), but not among the patients with undetectable levels of both these antigens. Serum levels of both preS1 (p < 0.005) and preS2 (p < 0.001) antigens were found to be significantly higher in delta-positive HBsAg-positive carriers than in patients with HBV infection uncomplicated by HDV. In addition to confirm previous observations that the detection of both preS antigens in HBsAg-positive sera is independent of HBV replication, these findings clearly show that HDV infection requires not only the presence of HBsAg, but also the presence of preS peptides, and seem to suggest a low susceptibility of HBsAg-positive carriers with low or undetectable synthesis and secretion of HBV surface proteins to delta superinfection.

Adult↗

Detection of antibodies to HCV in haemodialysis patients using two second generation ELISA tests.

Ortho HCV Elisa Test System 2nd Generation and Abbott HCV EIA 2nd Generation tests were used in 293 sera collected from dialysis patients in order to determine the prevalence of anti-HCV in this risk group and the sensitivity of the two tests. The agreement between the two tests employed was 98.3%. All reactive sera were confirmed using Ortho Riba and Abbott Supplemental tests. 91.9% sera were confirmed positive by Ortho RIBA and 100% by Abbott Supplemental test. The anti-HCV prevalence in haemodialysis patients increased with age, duration of dialysis treatment and number of transfusions. Our study confirms the higher prevalence of anti-HCV in haemodialysis patients using 2nd generation tests and their specificity.

Adult↗

Long-term immunogenicity safety and efficacy of a recombinant hepatitis B vaccine in healthy adults.

Two hundred healthy adults seronegative for HBV markers received three 10 or 20 mcg injections of a vaccine formulated from HBsAg produced by a recombinant strain of the yeast Saccharomyces cerevisiae. The vaccine was administered intramuscularly at 0, 1, and 6 months in the deltoid region. The seroconversion rates, expressed in GMT/IU/1 were determined at 1, 2, 6, 7, 12, 24, 36 and 48 months following the initial injection. No severe or serious adverse reactions attributable to the HB vaccines were observed in any subject. The seroconversion rates following the 20 mcg dose of recombinant vaccine were always higher than those observed after the 10 mcg dose, but the differences were not statistically significant. Also the GMT values were lower after the 10 mcg dose of vaccine. Females showed a higher anti-HBs response than males; an age-dependent effect was observed in the anti-HBs response as regards both the percentage of responders and the antibody concentrations in the serum. No adverse reactions to the vaccine were observed. The rDNA vaccine did not induce a response to yeast-derived impurities and did not increase anti-yeast IgE antibody titres. The results of this study have shown that the Amgen rDNA vaccine is safe and clinically well tolerated, and that it provides protection against infection and disease. A vaccination dose of 20 mcg appears more advantageous for healthy adult subjects.

Adolescent↗

Influence of free testosterone on antigen levels of plasminogen activator inhibitor-1 in premenopausal women with central obesity.

Women with upper body obesity are at increased risk for cardiovascular disease (CVD). Several studies have demonstrated a reduced fibrinolytic activity in these patients, mainly due to an enhanced activity of plasminogen activator inhibitor-1 (PAI-1). Since an increase of androgenic activity is a feature of central obesity in women, the present study was aimed at evaluating the possibility of a relationship between androgens and PAI-1 (antigen and activity) in 20 premenopausal women, 10 with upper body obesity and 10 controls. In obese women, PAI-1 antigen showed a positive Pearson correlation with free testosterone (FT), insulin, c-peptide, triglycerides (TG), and waist to hip ratio (WHR) (P less than .01), whereas PAI-1 activity correlated positively only with insulin and WHR (P less than .01). In control women, PAI-1 antigen and activity were positively related only to TG (P less than .01). When we applied the multiple regression model with stepwise backward method to our data, both PAI-1 antigen and activity did not maintain any significant association. However, when the data from both the groups were pooled (n = 20), and PAI-1 antigen was considered as the dependent variable, body weight (Sig T = 0.0001), TG (Sig T = 0.0053), FT (Sig T = 0.013), and luteinizing hormone (LH) (Sig T = 0.0474) met the stepwise criteria, suggesting an independent effect of each of these parameters on PAI-1 antigen. On the other hand, when PAI-1 activity was tested as the dependent variable, only body weight maintained a significant relationship with this parameter (Sig T = 0.0006).(ABSTRACT TRUNCATED AT 250 WORDS)

C-Peptide↗