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Biomedical subjects

M Silvestri

Publications and source records attributed to M Silvestri.

At least 19 recordsLinked to original sources
PubMed1999

Plasma levels of apolipoprotein E and genetic markers in elderly patients with Alzheimer's disease.

Besides apolipoprotein E (APOE) polymorphism, whose association with Alzheimer's disease (AD) has been confirmed in most of the numerous population samples studied, other markers have been investigated. In most cases the association firstly described was not confirmed in subsequent works. Since it is important to examine these associations in as many populations as possible, we investigated APOE, APOC1, APOC2, alpha-1 antichymotrypsin (ACT) and presenilin-1 (PS-1) polymorphisms in a series of elderly patients with late-onset sporadic AD from Northern Italy and in a sex and age-matched control group. We could not confirm the significantly higher frequency of the ACT*A allele among carriers of APOE e*4 allele described elsewhere, although a similar trend was observed. The APOC2 and the PS-1 distributions were similar between patients and controls. However, we observed a significant difference in the genotype and allele frequencies of APOE and APOC1: patients had higher e*4 and C1*2 allele frequencies. This finding confirms the important role for APOE in AD occurrence. In addition, APOC1 seems to be an interesting marker because, though in strict linkage disequilibrium with APOE, it seems to play an independent role in AD risk. In contrast to previously reported data, plasma apoE concentrations were similar in patients and in controls. An interaction between APOE and APOC1 polymorphisms and apoE levels was observed in patients: subjects carrying the APOE E3/E2 or the APOC1 2-2 genotype have higher apoE concentrations than those who do not.

Aged↗
PubMed1999

Radial force of coronary stents: a comparative analysis.

High radial force has become an essential feature of new coronary stents. These stents are expected to exhibit sufficient radial force and minimum radial recoil when deployed in atheromatous lesions of various morphologies. The aim of this study was to compare the radial force of 17 coronary stents in vitro (Anglodynamics, ACS Multilink, AVE Micro II and GFX, Bard XT, Biocompatibles PC, Cook GR II, Cordis Crossflex, Hexacath Freedom, Johnson & Johnson PS 153'PS 154, and Crown, Medtronic Wiktor and BeStent BEL-15, Saint-Come SC 1616, Scimed Nir 7 and 9). Two in vitro mechanical tests were performed to assess the stent radial force. The first test measured the deformation of coronary stents in a V-stand by using a deformation controlled by a dynamometer based on a longitudinal generatrix. The precision was of 1 micron. This comparative test highlighted the appreciable variation in behavior of the range of tested stents in terms of resistance to local compression. The line graphs obtained show a very small (and in some cases nonexistent) purely elastic behavior area in the stents, with this result reflecting a small (<0.4 Newtons) range of forces applied to all stents. Above this value, the stents did not return to their size before compression and the line graph remains approximately linear for a long period. It was therefore possible to distinguish between two families of stents on the basis of the presence or absence of this elastic area. In the second test, the stent was deployed in a 3.0-mm elastic tube and a pressure gradient created between the interior and exterior of the tube. The precision was of 50 microns. A typical line graph of the pressure-diameter relationship was recognizable for a given stent. No difference in behavior between the different coronary stents was noted up to 0.3 x 10(5) Pa; subsequently, after 0.3 x 10(5) Pa, sizable deformation differences were visible between the least resistant stent, the BeStent BEL-15, and the most resistant stent, the Crossflex.

Evaluation Studies as Topic↗
PubMed1999

Budesonide down-regulates eosinophil locomotion but has no effects on ECP release or on H2O2 production.

Treatment of allergic asthma with inhaled corticosteroids results in local down-regulation of proinflammatory cytokine synthesis and in marked decrease in tissue eosinophilia. Blood concentrations of inhaled corticosteroids, although significantly lower than those measured in the lung, may still have antiinflammatory effects on circulating eosinophils, reducing their ability to migrate. The aim of our study was to evaluate in vitro the activity of budesonide on blood eosinophils by measuring their chemotactic response, eosinophil cationic protein (ECP) release, and hydrogen peroxide (H2O2) production in the presence of different drug concentrations similar to those obtained at airway level (10(-8) and 10(-7) M) and at blood level (10(-10) and 10(-9) M). Partially purified blood eosinophils, isolated from 23 asthmatic subjects, were used to evaluate the activity of budesonide on: (1) chemotaxis toward the activated fifth component of complement (C5a, 0.1 microg/ml) or recombinant human (rh) interleukin (IL)-5 (200 pg/ml), (2) ECP release by cells stimulated with tetradecanoylphorbol acetate (TPA) and (3) H2O2 production by TPA-activated cells. The chemotactic response to C5a was down-regulated significantly by budesonide only by the highest concentrations tested (10(-8) and 10(-7) M); differently, budesonide was effective in inhibiting eosinophil migration toward rhIL-5, at all concentrations tested (p < 0.01, each comparison). By contrast, no drug-induced modifications were observed in ECP release or in H2O2 production (p > 0.05, each comparison). We conclude that concentrations of budesonide similar to those obtained in vivo are effective in inhibiting eosinophil locomotion but not in down-regulating the release of reactive oxygen species and granule-associated proteins.

Administration, Topical↗
PubMed1999

Orally exhaled nitric oxide levels are related to the degree of blood eosinophilia in atopic children with mild-intermittent asthma.

Increased levels of nitric oxide have been found in expired air of patients with asthma, and these are thought to be related to the airway inflammatory events that characterize this disorder. Since, in adults, bronchial inflammatory changes are present even in mild disease, the present study was designed to evaluate whether a significant proportion of children with mild-intermittent asthma could have increased exhaled air NO concentrations. Twenty-two atopic children (aged 11.1+/-0.8 yrs) with mild-intermittent asthma, treated only with inhaled beta2-adrenoreceptor agonists on demand and 22 age-matched controls were studied. NO concentrations in orally exhaled air, measured by chemiluminescence, were significantly higher in asthmatics, as compared to controls (19.4+/-3.3 parts per billion (ppb) and 4.0+/-0.5 ppb, respectively; p<0.01). Interestingly, 14 out of 22 asthmatic children had NO levels >8.8 ppb (i.e. >2 standard deviations of the mean in controls). In asthmatic patients, but not in control subjects, statistically significant correlations were found between exhaled NO levels and absolute number or percentage of blood eosinophils (r=0.63 and 0.56, respectively; p<0.01, each comparison). In contrast, exhaled NO levels were not correlated with forced expiratory volume in one second (FEV1) or forced expiratory flows at 25-75% of vital capacity (FEF25-75%) or forced vital capacity (FVC), either in control subjects, or in asthmatic patients (p>0.1, each correlation). These results suggest that a significant proportion of children with mild-intermittent asthma may have airway inflammation, as shown by the presence of elevated levels of nitric oxide in the exhaled air. The clinical relevance of this observation remains to be established.

Adolescent↗
PubMed1998

Airway eosinophilic inflammation and bronchial hyperresponsiveness after allergen inhalation challenge in asthma.

Allergen exposure in atopic asthmatic patients is associated with recruitment and activation of eosinophils in the airways. Once activated, eosinophils release toxic products, including the eosinophil cationic protein (ECP), able to damage bronchial structures and to increase bronchial hyperresponsiveness. With this background, the present study was designed to evaluate whether ECP levels in bronchoalveolar lavage (BAL) fluid could reflect, better than BAL eosinophil counts, the cellular activation that follows allergen exposure in atopic asthmatics. Twenty-two atopic patients attended the laboratory on two separate days. On the 1st day, they underwent methacholine (MCh) inhalation challenge to detect the degree of nonspecific bronchial hyperresponsiveness. On the 2nd day, they underwent fiberoptic bronchoscopy and BAL, at baseline or 4-6 h after allergen inhalation challenge. In this latter patient group, MCh challenge was repeated 3-5 h after allergen challenge, 1 h before fiberoptic bronchoscopy. The analysis of the mean baseline FEV1 values and the degree of bronchial reactivity to MCh (MCh Pd20) on the 1st study day did not demonstrate differences between the two patient groups (p > 0.1, each comparison). In addition, in the allergen-challenged group, MCh Pd20 was decreased significantly after allergen challenge (151.4 micrograms/ml and 67.6 micrograms/ml, respectively, before and after challenge; p < 0.05). Evaluation of the different BAL cell types demonstrated that the proportions of eosinophils and epithelial cells were increased significantly in the allergen-challenged group compared with the group evaluated at baseline (p < 0.01 and p < 0.05, respectively). Moreover, ECP levels, corrected by the correspondent albumin levels (ECP/Alb), were higher in the allergen-challenged group compared with the group evaluated at baseline (p < 0.05). In addition, although a positive correlation was demonstrated between BAL eosinophil percentages and ECP/Alb values (r = 0.72, p < 0.05) in the group evaluated at baseline, no links were found between these parameters in the allergen-challenged group (p > 0.1). However, in this latter group, a weak positive correlation was demonstrated between eosinophil percentages and delta Mch, i.e., the increased non-specific bronchial reactivity, which is observed after allergen challenge (r = 0.55; p < 0.05). Thus, in stable asthmatic patients an ongoing activation of eosinophils parallels their migration, but this eosinophilic inflammation is not strictly related to bronchial reactivity to Mch. By contrast, after allergen inhalation challenge, eosinophil recruitment and activation seem to follow different temporal kinetics, and eosinophilic inflammation may be partially associated with the degree of airway hyperresponsiveness.

Adolescent↗
PubMed1998

Salmeterol enhances the inhibitory activity of dexamethasone on allergen-induced blood mononuclear cell activation.

The possibility that salmeterol could interfere with the inhibitory effect of glucocorticosteroids on allergen-induced activation of leukocytes was assessed in cultures of human blood mononuclear cells (BMCs). BMCs, recovered from 27 patients (21 +/- 4 years of age) sensitized to Dermatophagoides pteronyssinus (Der p), were incubated with a purified Der p extract (10 micrograms/ml) for 7 days in the presence of salmeterol (10(-8) and 10(-7) M) and/or dexamethasone (10(-10) and 10(-9) M). BMC proliferation and cytokine release were respectively tested by [3H]thymidine incorporation and EASIA. Stimulation with Der p extract induced a significant BMC proliferation (Der p 18.7 +/- 1.9 cpm x 10(3), control 1.8 +/- 0.3 cpm x 10(3), p < 0.01) which was significantly inhibited both by salmeterol and dexamethasone (p < 0.05, each comparison). The inhibition of BMC proliferation induced by dexamethasone (10(-9) M) was significantly enhanced by salmeterol 10(-7) M (p < 0.05). Evaluation of cytokine levels in BMC supernatants showed that Der p extract significantly increased the release of granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta and IL-2 (p < 0.001, each comparison). Salmeterol (10(-7) M) or dexamethasone (10(-9) M) induced a similar, statistically significant, downregulation of GM-CSF release (p < 0.05, each comparison) and induced a slight, not significant, decrease in the production of IFN-gamma, TNF-alpha, IL-1 beta and IL-2 (p > 0.05 each comparison). Interestingly, salmeterol (10(-7) M) significantly enhanced the inhibitory activity of dexamethasone (10(-9) M) on the release of GM-CSF, TNF-alpha, IL-1 beta and IL-2 (p < 0.05, each comparison) but not of IFN-gamma (p > 0.05). Thus beta 2-adrenoceptors may enhance the inhibitory activity of low doses of corticosteroids on allergen-induced BMC activation.

Adrenergic beta-Agonists↗
PubMed1998

Downregulation of the expression of intercellular adhesion molecule (ICAM)-1 on bronchial epithelial cells by fenoterol, a beta2-adrenoceptor agonist.

Inflammatory airway disorders, such as asthma and chronic bronchitis, are characterized by overexpression of adhesion molecules on airway epithelial and endothelial cells. This phenomenon is associated with increased adherence and activation of polymorphonuclear leukocytes (PMNs). With the knowledge that beta2-adrenoceptor agonists demonstrate some anti-inflammatory activity in vitro, the present study was designed to evaluate whether fenoterol could interfere with adhesion molecule expression on airway epithelium. Human bronchial epithelial cells (HBECs), obtained by protease digestion from surgically resected bronchi, were stimulated with human recombinant interferon-gamma (rh IFN-gamma) in the presence of (a) fenoterol (10(-12)-10(-5) M); (b) dexamethasone (10(-12)-10(-5) M); and (c) fenoterol and dexamethasone. Because desensitization after high-dose exposure to agonists has been described for many membrane-associated receptors, in additional sets of experiments HBECs were preexposed to fenoterol and, as control, to dexamethasone for 8 hr, then washed and stimulated with rh IFN-gamma in the presence of fresh drugs. The cells were harvested after 24-hr culture and stained by specific monoclonal antibodies. The intensity of intercellular adhesion molecule-1 (ICAM-1) expression was then measured by flow cytometry analysis and expressed as mean fluorescence channel (mfc). The significant increase in ICAM-1 expression on HBECs induced by rh IFN-gamma was inhibited, in a dose-dependent manner, by the two drugs, but fenoterol was more efficient than dexamethasone at all of the concentrations tested (p < 0.05, all comparisons). In addition, the inhibitory activity of fenoterol was not enhanced by the simultaneous presence of dexamethasone in rh IFN-gamma-stimulated HBEC cultures (p > 0.05, all comparisons). Finally, preexposure to fenoterol or to dexamethasone did not induce any modification of the inhibitory effect of the two drugs on ICAM-1 expression (p > 0.05, all comparisons). These results suggest that clinical efficacy of fenoterol in patients with obstructive lung disease may include downregulation of adhesion molecule expression on airway epithelial cells.

Adrenergic beta-Agonists↗
PubMed1998

Blood eosinophilia and degree of sensitization to house dust mites in preschool and school children with asthma.

In allergic asthma, there is convincing evidence that changes in eosinophil and lymphocyte state of activation in blood may reflect disease activity. We evaluated whether simple blood eosinophil or lymphocyte counts in atopic children with asthma could reflect the degree of allergic sensitization. Seventy-six asthmatic children, sensitized to house dust mites (HDM), in stable conditions at the time of the study, and 53 sex- and age-matched controls (CTR) were studied. As compared to CTR, allergic patients showed higher eosinophil numbers and percentages (p < 0.001) but similar lymphocyte numbers and proportions (p > 0.1). Both in CTR and in allergic patients, eosinophil counts did not correlate with lymphocyte counts (p > 0.05; each comparison) but positive correlations were observed between eosinophil numbers and percentages and paper radio immunosorbent test (PRIST) levels or radio-allergo sorbent test (RAST) classes (p < 0.001; each comparison). When allergic asthmatic individuals were subdivided according to their age into two subgroups (Gr), no differences were found in eosinophil and lymphocyte counts and in PRIST levels and RAST values between Gr1 (< or =5 years old [preschool children]) and Gr2 (>5 years old [school children]) (p > 0.05; each comparison). Interestingly, although positive correlations between eosinophil counts and PRIST levels were found in both subgroups (p < 0.05; each comparison), only in Gr2 did eosinophil counts correlate positively with RAST classes (p < 0.001). No correlations between lymphocyte counts and PRIST levels or RAST classes were demonstrated (p > 0.05; each comparison). These data suggest that although blood eosinophilia was similar in preschool and in allergic asthmatic school children sensitized to HDM, only in the oldest children did blood eosinophil counts appear to be related to the degree of HDM-specific sensitization.

Adolescent↗
PubMed1997

Coronary artery stenting without anticoagulation, aspirin, ultrasound guidance, or high balloon pressure: prospective study of 1,051 consecutive patients.

Between March 1994 and November 1995, 1,212 coronary stents were implanted in 1,051 consecutive patients at our institution with the following protocol: daily pre- and poststenting treatment with ticlopidine 500 mg without aspirin, implantation under angiographic guidance, without ultrasound, with semi-compliant balloons inflated at 10 bars. Stenting was indicated after failure of balloon angioplasty (bail-out, dissection, elastic recoil) in 27% of the patients and considered as elective (de novo, restenosis, chronic occlusion, saphenous vein grafts) in 73% of the cases. During the 30-day follow-up period, stent thrombosis occurred in 11 patients (1.0%) and vascular access-site complications in three patients (0.3%). Thirteen patients (1.1%) died, 10 from previous left ventricular failure, 3 (0.3%) from subacute thrombosis. Multivariate analysis revealed that the size of the last balloon used was associated with subacute stent thrombosis Thus, in nonselected patients, placement of coronary stents may be safely achieved without use of warfarin, post procedural heparin, high balloon pressure, or ultrasound guidance. Antiplatelet therapy with ticlopidine and angiographic guidance result in a stent thrombosis rate of 1% and a vascular complication rate of 0.3%.

Adult↗
PubMed1997

Mineral oil lipoid pneumonia in a child with anoxic encephalopathy: treatment by whole lung lavage.

We describe a case of exogenous lipoid pneumonia in a child with anoxic encephalopathy who was taking mineral oil for constipation. Computed tomography produced images suggesting this condition, and the diagnosis was confirmed by demonstrating the presence of lipid-laden alveolar macrophages in the bronchoalveolar lavage fluid. Despite discontinuing the offending agent, the pulmonary infiltrates did not improve; however, successful resolution was obtained by whole lung lavage.

Bronchoalveolar Lavage↗
PubMed1997

Salmeterol inhibits the allergen-induced mononuclear cell proliferation and downregulates GM-CSF release and HLA-DR expression by monocytes.

beta 2-adrenoceptor agonists are known to attenuate several functions of human mononuclear cells in response to activation. Since monocytes and lymphocytes play a major pathogenetic role in allergic asthma, this study was designed to evaluate the hypothesis that salmeterol, a beta 2-adrenoceptor agonist with a long duration of action, could inhibit in vitro the allergen-induced activation of blood mononuclear cells (BMCs). BMCs were collected from subjects sensitized to Dermatophagoides pteronyssinus (Der p) and incubated with a purified Der p allergen extract to evaluate the ability of salmeterol to downregulate; (a) BMC proliferation; (b) IL-2 receptors (r) and HLA-DR surface antigen (ag) expression; (c) cytokine release. Der p induced a significant BMC proliferation (P < 0.01), associated with increased expression of HLA-DRag and IL-2r (P < 0.05) and with enhanced release of IL-2, GM-CSF, IL-1 beta, TNF-alpha and IFN-gamma (P < 0.01, each comparison). Salmeterol (10(-8)-10(-6) M) significantly inhibited, in a dose dependent manner, the Der p-induced BMC proliferation, reducing (at 10(-7) M) HLA-DRag expression on monocytes and GM-CSF release (P < 0.05, each comparison). These data demonstrate that beta 2-adrenoceptor-mediated suppression of allergen-induced BMC activation is associated with inhibition of cytokine release and of surface molecule expression, which are involved in the interaction between T-lymphocytes and antigen-presenting cells.

Adrenergic beta-Agonists↗
PubMed1997

Bronchial and bronchoalveolar inflammation in single early and dual responders after allergen inhalation challenge.

To characterize the cellular inflammation at the bronchial and bronchoalveolar levels, we evaluated 43 patients with asthma who were sensitized to house dust mites. On 2 consecutive days patients underwent methacholine challenge and allergen bronchial challenge. In addition, 6, 24, or 72 h after allergen challenge, fiberoptic bronchoscopy with bronchial lavage (BL) and bronchoalveolar lavage (BAL) was performed. Patients belonging to the 6-h, 24-h, or 72-h group were divided further into two subgroups: those with isolated early response to allergen (LAR-), and those with dual response to allergen (LAR+). The percentage of eosinophils and of epithelial cells in BAL fluid was significantly higher in LAR+ than in LAR- patients in the 6-h group (p < 0.05, each comparison), but not 24 or 72 h after (p > 0.05, each comparison). Similarly, the proportion of BL eosinophils was also higher in LAR+ than in LAR- patients, both in the 6-h and in the 24-h group (p < 0.05, each comparison). In addition, increased proportions of BL neutrophils were present in the LAR+ patients belonging to the 24-h group (p < 0.05). Comparing "proximal" = BL vs "distal" = BAL data, we found a significantly higher proportion of epithelial cells in BL compared with BAL, in both LAR- and LAR+ subjects, either 6, or 24, or 72 h after challenge (p < 0.01, each comparison) and increased percentages of BL neutrophils and eosinophils in LAR+ patients (p < 0.05, each comparison), but not in LAR- patients, in the 24-h group. The percentages of BL or BAL macrophages and lymphocytes did not differ significantly among the different patient groups. These data indicate that the development of LAR after allergen inhalation challenge is associated with an early recruitment of eosinophils and with epithelial desquamation in the airways. In addition, after allergen challenge epithelial desquamation is more pronounced in the proximal than in the distal airways, independently of the type of bronchial response.

Adolescent↗
PubMed1997

Frequency and specific sensitization to inhalant allergens within nuclear families of children with asthma and/or rhinitis.

OBJECTIVE: The purpose of this study was to investigate the frequency of allergy in 85 families of pediatric patients with asthma and/or rhinitis. METHODS: Families enrolled were drawn according to a table of randomization, from those whose children were referred the outpatient clinic of the Pulmonology Department of Gaslini Institute (Genoa, Italy). In patients and in both their mothers and fathers, allergic sensitization to the three most common classes of inhalant allergens (house dust mites, pollens, and animal danders) was evaluated by skin prick test. RESULTS: As compared with their parents, children showed a similar prevalence of positive skin prick test (50.0% and 58.8%, respectively; chi 2 = 1.4; P > .1), but a significantly higher frequency of specific sensitization to house dust mites, pollens, or pets (P < .05, each chi 2). These differences were at least partially related to the higher frequency of polysensitization (i.e., sensitization to more than one class of allergens) in children than in their parents [chi 2 = 4.2, odds ratio (OR) = 2.3, 95% confidence interval (CI95%) = 1.0 to 5.1; P < .05). In addition, both in children (chi 2 = 5.8, OR = 11.3, CI95% = 1.4 to 81.5; P < .05] and in their parents (chi 2 = 7.4, OR = 4.8, CI95% = 1.5 to 16.7; P < .01), allergy to pollens was less frequent in monosensitized than in polysensitized families, while the prevalence of sensitization to house dust mites was similar in monosensitized and in polysensitized families. The analysis of the role of parental sensitization in the development of allergy in the offspring demonstrated that the prevalence of allergic children: (1) seemed to be higher, without reaching statistical significance, in families with sensitized parents than in those with non-sensitized parents (chi 2 = 0.41, P > .1) and (2) was higher in families with one or both polysensitized parents than in those with one or both monosensitized parents (chi 2 = 4.5, OR = 4.0, CI95% = 1.1 to 15.6; P < .05). In addition, within each family, the coincidence of sensitization to house dust mites was more frequent than that to pollens (60.0% and 36.0%, respectively; chi 2 = 7.6, OR = 4.5, CI95% = 1.5 to 14.3; P < .01), and it was not influenced by the number of parents sensitized to same allergen. CONCLUSION: These data support the concept that, in addition to genetic predisposition, other factors (i.e., environmental exposure) may influence the development of specific sensitization in children with respiratory symptoms. The different sensitization found in this study between children and their parents occurred in a generation span, so as it is more likely to be related to environmental changes than to genetic factors.

Administration, Inhalation↗
PubMed1997

Adult onset Krabbe's leukodystrophy: a report of 2 cases.

Krabbe's disease with adult onset is rare; neurological symptoms begin in childhood or at a juvenile age. Two brothers with adult onset of the disease are here reported; 1 sibling developed parapareto-ataxic gait while the other was asymptomatic. Magnetic resonance imaging showed areas of demyelination in the white matter of the brain, while nerve conduction was completely normal. In both patients deficiency of galactosylceramide beta-galactosidase was comparable to the infantile form.

Adult↗
PubMed1997

Cytomegalovirus glycoprotein B-specific antibody analysis using electrochemiluminescence detection-based techniques.

An electrochemiluminescence technique was used to develop versatile and sensitive assay strategies for determination of seroreactivities against biologically important cytomegalovirus neutralization epitopes expressed on glycoprotein B. Indirect binding assays showed wide linear assay ranges and revealed that serum samples diluted in parallel with a monoclonal antibody-based standard, simplifying quantitative analytical assessments.

Antibodies, Viral↗
PubMed1996

Retrograde left main stenting.

Percutaneous transluminal coronary angioplasty of protected left main coronary artery stenosis is usually performed by an antegrade approach. In this case report, we describe left main coronary artery stenting by a retrograde approach through a saphenous venous graft in a patient in whom the antegrade approach was considered less appropriate due to chronic ostial occlusion.

Aged↗