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G Valesini

Publications and source records attributed to G Valesini.

At least 73 records · Page 4Linked to original sources
PubMed1997

Interferon alpha for ocular Behçet's disease.

PURPOSE: To investigate the therapeutic role of interferon alpha in ocular Behçet's disease. METHODS: Three patients with B- or C-hepatitis and ocular sight-threatening Behçet's disease unresponsive to steroids were treated subcutaneously with interferon alpha 3 x 10(6)/unit three times per week for a mean period of 22 months (range: 12-31 months). The course of ocular and systemic lesions was recorded and compared with a similar pre-treatment period. RESULTS: At least a 50% reduction in the number of ocular relapses was observed in all the patients (mean relapse/month: 0.41 versus 0.16 in the pre- and in-treatment period, respectively) while during therapy also each relapse lasted less in all subjects. A reduction of steroid dependence was observed in all patients, while no significant side-effects were related to interferon alpha administration. Two patients who tried to stop interferon alpha therapy showed after a mean period of 12.5 days a recurrence of diffuse uveitis and, one of them experienced oral and genital aphthae as well. CONCLUSION: In patients with Behçet's disease interferon alpha seems to be a useful alternative therapy for sight-threatening ocular involvement.

Adult↗
PubMed1997

Differential risk of non-Hodgkin's lymphoma in Italian patients with primary Sjögren's syndrome.

OBJECTIVE: To assess the incidence of non-Hodgkin's lymphoma (NHL) and estimate the relative risk (RR) of developing lymphoproliferative complications in a large population of Italian patients with Sjögren's syndrome (SS) and to ascertain if any difference exists between the north and centre-south of Italy. METHODS: Differential relative risks of NHL were obtained by comparing the number of observed cases with cases identified on the basis of age-sex-time specific incidence rates extracted from regional cancer registries. RESULTS: Among the 331 patients with SS studied, 9 cases of NHL occurred, while no lymphoid malignancy appeared in patients with overlapping connective tissue disease (secondary SS) or in males with primary SS. As the number of NHL cases identified on the basis of the rate in the cancer registries would have been 0.27, the RR is 33.3 (p < 0.001). The incidence rate of NHL in Italian patients with SS is about 5.1/1000 person-years. 5.4/1000 per year in the north of the country and 4.8/1000 per year in the centre-south. The relative risks are, respectively, 34.7 and 32.5. CONCLUSION: Italian patients with primary SS have increased risk of developing NHL. In this group, the absence of a significant difference between the north and the centre-south of Italy contrasts with the higher incidence of NHL in the general population of northern regions and strengthens the direct connection between primary SS and NHL.

Adult↗
PubMed1996

Epitope specificity of anti-HIV antibodies in human and murine autoimmune diseases.

This article reports the HIV epitope specificity of antibodies present in the sera of HIV-negative patients with autoimmune diseases. Recombinant gp120 and a panel of synthetic peptides derived from the amino acid consensus sequences of either related (gp120, gp41, and p24) or unrelated (Mage-1, necdin, heat shock protein [65 kDa], and amyloid) HIV proteins were tested by a specific ELISA. The first set of experiments performed on four patients with Sjögren's syndrome (SjS) and four patients with systemic lupus erythematosus (SLE) revealed a significant anti-gp120 antibody reactivity in autoimmune patients when compared to healthy HIV-negative controls. Moreover, such binding could be almost completely inhibited by preincubation with free gp120. A significant anti-p24 reactivity was observed in 18 of 29 sera from SjS patients and in 13 of 25 sera from SLE patients, while anti-gp41 was observed only in 3 of 14 SjS and in 2 of 20 SLE-affected patients. Similar analyses were performed in the murine model of autoimmunity, showing that sera from MRL/lpr mice were able to bind all HIV-related peptides in an age-dependent manner. The analysis of a panel of HIV-unrelated peptides showed that SLE as well as MRL/lpr sera bind both HIV-related and unrelated peptides, while SjS sera failed to do so, revealing the polyclonal nature of the SLE and MRL/lpr repertoire and the oligoclonal reactivity of SjS sera. This is also supported by inhibition experiments, which showed that SLE, but not SjS, sera competitively inhibited the binding to HIV gp120 peptide of sera from autoimmune MRL/lpr mice. These results indicate that an overlapping polyclonal repertoire is present in both SLE and MRL/lpr sera, while the oligoclonal specificity of SjS antibodies may be related to a specific, nonpolyclonal, activation against putative retroviral antigens.

Amino Acid Sequence↗
PubMed1996

Twenty-four hour heart period variability in systemic sclerosis.

OBJECTIVE: In patients with systemic sclerosis (SSc), an autonomic dysfunction has been implicated in the pathogenesis of Raynaud's phenomenon and gastrointestinal symptoms. To evaluate cardiovascular autonomic function we analyzed the heart rate variability (HRV) on 24 h electrocardiogram recordings. METHODS: In 50 patients diagnosed with SSc and 24 control subjects HRV was analyzed for both frequency and time domain. RESULTS: Frequency domain analysis showed reduction of low frequency and high frequency values in the patients with SSc compared to controls (5.52 +/- 0.74 vs 6.04 +/- 0.78 In(ms2), p = 0.007; and 4.17 +/- 0.97 vs 4.74 +/- 0.97 In(ms2), p = 0.021, respectively). Analysis in time domain showed no significant differences in any variable between groups. There were no significant differences between the diffuse and the limited form of SSc. Number of ventricular ectopic beats, prevalence of frequent ventricular ectopy, and supraventricular tachycardia episodes were increased in the patients with SSc compared to controls. CONCLUSION: Spectral analysis of heart period variability suggests cardiovascular autonomic dysfunction in patients with SSc. Better understanding of this complication could help delineate new strategies for the treatment of SSc.

Adult↗
PubMed1996

Eosinophil cationic protein serum levels and allergy in chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is a syndrome of uncertain etiopathogenesis characterized by disabling fatigue associated with a variable number of somatic and/or neuropsychologic symptoms. In patients with CFS, several immunologic abnormalities can be detected, including a higher prevalance of allergy. The aim of this study was to determine whether CFS patients, well studied for their allergy profile, show signs of eosinophil activation, as detectable by the measurement in serum of eosinophil cationic protein (ECP) levels. In 35 consecutive CFS outpatients (diagnosis based on the Centers for Disease Control case definition), ECP was measured in serum by a competitive enzyme immunoassay (ECP-FEIA kit, Kabi Pharmacia Diagnostics, Uppsala, Sweden). Fourteen disease-free subjects with no history of CFS or allergy were selected as controls. ECP serum levels were significantly higher in CFS patients than in controls (18.0 +/- 11.3 micrograms/l vs 7.3 +/- 2.1 micrograms/l; P < 0.01). In the CFS population, the prevalence of RAST positivity to one or more allergens was 77%, while no control showed positive RAST. Twelve of the 14 CFS patients with increased ECP serum levels were RAST-positive. However, CFS RAST-positive patients had no significantly higher ECP serum levels than CFS RAST-negative patients (19.3 +/- 12.4 micrograms/l vs 13.6 +/- 3.7 micrograms/l; P = 0.4). This is the first report of increased serum levels of ECP in CFS. On the basis of the available data, it is discussed whether eosinophil activation has a pathogenetic role in CFS or is linked to the frequently associated allergic condition, or, finally, whether a common immunologic background may exist for both atopy and CFS.

Adult↗
PubMed1996

Anticardiolipin and anti-beta 2-GPI are two distinct populations of autoantibodies.

This study has been undertaken to assess whether anticardiolipin and anti-beta 2-GPI are two distinct populations of (auto)antibodies, and to clarify whether the beta 2-GPI region critical for phospholipid binding is also crucial for anti-beta 2-GPI reactivity. Fourteen of the 62 anticardiolipin (aCL) ELISA positive sera (22.6%) were positive for anti-beta 2-GPI by immunoblotting, 42 (67.7%) for aCL using TLC immunostaining. IgG fractions from 5 sera gave the same anticardiolipin reactivity detected by TLC immunostaining in the corresponding sera. All anti-beta 2-GPI-positive sera were reactive with the phenylthiocarbamyl derivative of the protein, indicating that binding of phenylisothiocyanate with lysine residues does not modify the molecule antigenicity. In addition, incubation of IgG fractions with the phospholipid binding site did not modify reactivity with beta 2-GPI. These findings demonstrate that: a) "true" antiphospholipid antibodies are detectable in patients' sera; b) aCL and anti-beta 2-GPI have a different immunological profile; c) the beta 2-GPI phospholipid-binding site is not the region recognized by the antibodies.

Adult↗
PubMed1995

Saddle nose.

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Aged↗
PubMed1995

Plasma endothelin-1 levels, pulmonary hypertension, and lung fibrosis in patients with systemic sclerosis.

PURPOSE: To investigate the behavior of circulating endothelin (ET)-1 concentrations in patients affected by systemic sclerosis, and to elucidate the possible relationships existing in this disease among plasma peptide levels, pulmonary hypertension, and lung fibrosis. PATIENTS AND METHODS: Circulating ET-1 levels were determined by reverse-phase, high-pressure liquid chromatography followed by sensitive radioimmunoassay in 20 patients affected by systemic sclerosis (18 women and 2 men, mean age 48.1 +/- 13.7 years) with or without pulmonary hypertension as evaluated by Doppler echocardiography, or lung fibrosis as measured by a score method based on lung examination by high-resolution computed tomography (HRCT). A group of 18 normal volunteers served as controls (15 women and 3 men, mean age 45.0 +/- 10.1 years). RESULTS: Plasma ET-1 levels were significantly higher (P < 0.001) in patients with systemic sclerosis (1.72 +/- 0.28 pg/mL) than in control subjects (0.63 +/- 0.06 pg/mL). Pulmonary artery systolic hypertension was detected in 10 patients (50%) with systemic sclerosis (56.2 +/- 18.0 mm Hg, range 37 to 97) versus none of the control subjects (30.2 +/- 2.2 mm Hg, P < 0.0001). Lung fibrosis was present in 12 patients (60%), with an HRCT overall score of 9.0 +/- 4.6. There were no significant differences in plasma ET-1 levels between patients with pulmonary hypertension (1.58 +/- 0.20 pg/mL) or without it (1.76 +/- 0.39 pg/mL, P = 0.188, not significant [NS]); or between patients with lung fibrosis (1.65 +/- 0.14 pg/mL) or without fibrosis (1.78 +/- 0.37 pg/mL, P = 0.290, NS). In particular, 6 patients had neither pulmonary hypertension nor lung fibrosis. In these patients, plasma ET-1 levels were similar compared with the others (1.85 +/- 0.49 versus 1.66 +/- 0.13, respectively; P = 0.180, NS). No correlations were observed between ET-1 levels and either pulmonary pressure levels or HRCT overall scores. CONCLUSIONS: The use of a sensitive assay, highly selective for ET-1, showed higher levels of circulating peptide in patients affected by systemic sclerosis than in control subjects. Neither pulmonary hypertension nor lung fibrosis was accompanied by a further rise in plasma ET-1 concentrations.

Adult↗
PubMed1995

Anti-beta 2-glycoprotein I antibodies: a marker of antiphospholipid syndrome?

Anticardiolipin (aCL) and anti-beta 2-glycoprotein I(anti beta 2GPI) antibodies have been shown in animal models as not cross-reacting antibody populations. This observation prompted us to prove if anti-beta 2GPI exist in human sera by using a reliable method and then to investigate if these are independent from aCl antibodies. We have developed a new ELISA for the detection of anti-beta 2GPI antibodies employing the coating of the protein in carbonate buffer to irradiated microtitre plates and the filtration of serum samples, that makes irrelevant the binding to the uncoated wells. IgG F(ab)2 fragments from IgG positive sera were shown bind beta 2GPI, providing that the binding was a specific antibody binding, mediated by the antigen binding site of the antibody molecule: moreover the antibodies were not able to differentiate native and delipidated beta 2GPI coated plates, making a possible role of a phospholipid contaminant unlikely. On the other hand, the phosphorus content of native as well as delipitated beta 2GPI was undetectable. IgG, but not IgM, anti-beta 2GPI antibodies were classically inhibited by the addition of soluble beta 2GPI, while cardiolipin liposomes appear to modify the reaction in a completely different way, possibly by the described interaction between cardiolipin and beta 2GPI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Insulin stimulates endothelin-1 secretion from human endothelial cells and modulates its circulating levels in vivo.

Endothelin-1 (ET-1) is a potent vasoactive and mitogenic peptide produced by the vascular endothelium. In this study, we evaluated whether insulin stimulates ET-1 secretion by human endothelial cells derived from umbilical cord veins and by human permanent endothelial hybrid cells Ea.hy 926. Moreover, to provide evidence that insulin may stimulate ET-1 secretion in vivo, plasma ET-1 levels were evaluated in 7 type II diabetic normotensive males (mean age, 54.3 +/- 4.0 yr) during 2-h hyperinsulinemic euglycemic clamps (287 pmol insulin/m2.min-1) as well as in 12 obese hypertensive males (mean age, 44.2 +/- 4.6 yr) before and after a 12-week period of caloric restriction. Our results showed that insulin stimulated ET-1 release from cultured endothelial cells in a dose-dependent fashion. ET-1 release persisted for 24 h and was also observed at physiological insulin concentrations (10(-9) mol/L). The insulin-induced ET-1 secretion was inhibited by genistein, a tyrosine kinase inhibitor, and by cycloheximide, a protein synthesis inhibitor, suggesting that it requires de novo protein synthesis rather than ET-1 release from intracellular stores. In the in vivo experiments, plasma ET-1 levels rapidly increased during euglycemic hyperinsulinemic clamps (from 0.76 +/- 0.18 pg/mL at time zero to 1.65 +/- 0.21 pg/mL at 60 min; P < 0.05) and persisted elevated until the end of insulin infusion (1.37 +/- 0.37 pg/mL at 120 min; P < 0.05 vs. time zero). In obese hypertensives, plasma ET-1 levels significantly decreased after 12 weeks of caloric restriction (from 0.85 +/- 0.51 to 0.48 +/- 0.28 pg/mL; P < 0.04). The decrease in body weight induced by caloric restriction was accompanied by a significant reduction in fasting insulin levels (from 167.2 +/- 94.0 to 98.9 +/- 44.9 pmol/L; P < 0.05) which correlated with the reduction in plasma ET-1 levels (r = 0.78; P < 0.003). In conclusion, our data show that insulin stimulates both in vitro and in vivo ET-1 secretion. Such interaction could play a significant role in the development of atherosclerotic lesions in hyperinsulinemic conditions.

Adult↗
PubMed1995

Increased rate of thrombin generation in hepatitis C virus cirrhotic patients. Relationship to venous thrombosis.

BACKGROUND: Venous thrombosis may complicate the clinical course of liver cirrhosis (LC), but the pathogenesis is still uncertain. We have previously demonstrated that antiphospholipid (aPL) antibodies were a risk factor for thrombosis. In the same study it was also evident that there was a higher prevalence of hepatitis C virus (HCV) infection in patients with thrombosis, and an association between anti-HCV positivity and aPL. METHODS: In a case-control study, 18 consecutive patients with LC, who had suffered from splanchnic venous thrombosis (n = 12), or thrombophlebitis (n = 6), were matched for age, sex, and degree of liver failure with 36 LC patients without thrombosis. RESULTS: In comparison to patients without thrombosis, patients with thrombosis had higher prevalence of HCV infection (p = 0.0027), positivity for aPL antibodies (p = 0.0003), and higher values of fragment F1+2, a marker of thrombin generation (p = 0.0083). While F1+2 values were similar in aPL (+) and aPL (-) patients, HCV patients had significantly higher values of F1+2 than patients with hepatitis B virus (HBV) infection and/or alcoholism (2.6 +/- 0.94 vs 1.5 +/- 0.66, p = 0.0001). CONCLUSIONS: These data suggest that in LC, HCV infection may contribute to clotting system activation, thus predisposing patients to venous thrombosis.

Adult↗
PubMed1994

Detection of antiphospholipid antibodies by immunostaining on thin layer chromatography plates.

There is increasing interest in the role of antiphospholipid antibodies in the so-called 'antiphospholipid antibody syndrome' (APS). The two major methods currently employed for detecting the autoantibodies are the solid phase ELISA and the LAI test (inhibition of phospholipid dependent coagulation assay). In our study we have tested the possibility of detecting antiphospholipid antibodies by immunostaining on thin layer chromatography (TLC) plates, since this technique permits the use of pure phospholipid molecules as antigen. Sera were collected from 20 patients with SLE without APS, 20 patients with APS, 20 anti-HIV positive subjects, ten patients with signs of APS but antiphospholipid negative (ELISA), 20 patients with syphilis and 40 matched blood donors. Results showed that only 72.3% of sera containing detectable levels of aCL antibodies in solid phase ELISA were also positive for aCL in TLC immunostaining; these discrepancies may be due to the presence of antibodies reacting with a protein complexed with phospholipid (beta 2-glycoprotein-I) or, alternatively, to the different antigenic presentation of phospholipids on chromatograms compared to the surface of microtitre wells. Furthermore, aCL monoclonal antibody CAL-3, as well as nine sera positive for aCL, also reacted with PS and PE. Previous absorption of these sera with CL micelles completely abolished the reactivity with PS and PE, demonstrating cross-reactivity among these three phospholipids. In conclusion, our findings reveal that TLC immunostaining is more specific, but less sensitive, than ELISA for the detection of antiphospholipid antibodies in human sera.

Antibodies, Anticardiolipin↗
PubMed1994

Immunization with anticardiolipin cofactor (beta-2-glycoprotein I) induces experimental antiphospholipid syndrome in naive mice.

Beta-2-GPI is a 50 kDa glycoprotein which is known to be a serum co-factor, with a role in determining the binding of pathogenic anticardiolipin antibodies to phospholipids. Immunization of naive mice with beta-2-GPI resulted in elevated levels of antibodies directed against negatively charged phospholipids (cardiolipin, phosphotidylserine, phosphatidylinositol). The presence of increased titres of antiphospholipid antibodies in the sera of the mice was later followed by prolonged activated partial thromboplastin time (APTT), thrombocytopenia, and when the mice were mated, by a high percentage of fetal resorptions in the uterus. These data point to the ability of beta-2-GPI to induce pathogenic anti-cardiolipin antibodies following active immunization.

Animals↗
PubMed1994

Central nervous system involvement in systemic lupus erythematosus: a new therapeutic approach with intrathecal dexamethasone and methotrexate.

In systemic lupus erythematosus (SLE), neurological involvement has been reported to occur with frequencies ranging from 14% (severe cases) to 83% (mild forms included). In spite of early diagnosis and aggressive treatment, neuropsychiatric SLE may represent a serious problem of management. We describe three cases, one with acute transverse myelitis, one with hemiparesis, and one with signs of focal and diffuse cerebral dysfunction, in whom improvement following intrathecal therapy with methotrexate and dexamethasone was observed.

Adolescent↗
PubMed1994

Chronic fatigue: a peculiar evolution of eosinophilia myalgia syndrome following treatment with L-tryptophan in four Italian adolescents.

We describe four Italian adolescents in whom a persistent, debilitating fatigue appeared after therapeutic ingestion of products containing L-tryptophan and subsequent to the development of a transient rise in eosinophil count and severe myalgia (Eosinophilia Myalgia Syndrome-EMS). Their clinical picture was indistinguishable from that of the so-called Chronic Fatigue Syndrome. A chronic fatigue may occur after diverse triggering agents and its represents the peculiar clinical evolution of these four paediatric cases of EMS.

Adolescent↗