Biomedical subjects
Publications and source records attributed to M Tomassini.
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BACKGROUND: Computed tomography has been shown to be useful in the evaluation of aortocoronary bypass grafts (CABG). This is the first prospective study to evaluate the accuracy of a new-generation scanner in the detection of patency and significant stenoses (>50% decrease in diameter) of venous and arterial grafts in patients with previous CABG. METHODS AND RESULTS: In 96 patients (80 males, mean age 62 years) with previous CABG, a multislice computed tomography (MSCT) scan was performed (collimation 16x0.625 mm). Patients with atrial fibrillation, renal failure, severe respiratory disease, severe heart failure, heart rate >70 bpm despite therapy, or unstable angina were excluded. A total of 285 conduits implanted on the native coronary arteries at the time of CABG were evaluated. MSCT data were analyzed by 2 independent radiologists and compared with the results of conventional angiography. Three patients were excluded from analysis. All conduits were judged evaluable in 84 patients. Among these patients, MSCT correctly diagnosed 54 occluded grafts and 4 significant stenoses on the body of the grafts. Of the 17 significant anastomotic lesions, MSCT correctly diagnosed 15. For these 84 patients, diagnostic accuracy was 99%, sensitivity was 97%, and specificity was 100%. When all 93 patients were considered, the sensitivity of MSCT in diagnosing significant stenoses was 96%. CONCLUSIONS: MSCT with the new-generation scanner allows for accurate assessment of venous and arterial conduits in patients with previous CABG with a high degree of sensitivity and specificity. Exclusion criteria and radiation exposure remain limitations of the method.
Parallel evolutionary algorithms, over the past few years, have proven empirically worthwhile, but there seems to be a lack of understanding of their workings. In this paper we concentrate on cellular (fine-grained) models, our objectives being: (1) to introduce a suite of statistical measures, both at the genotypic and phenotypic levels, which are useful for analyzing the workings of cellular evolutionary algorithms; and (2) to demonstrate the application and utility of these measures on a specific example-the cellular programming evolutionary algorithm. The latter is used to evolve solutions to three distinct (hard) problems in the cellular-automata domain: density, synchronization, and random number generation. Applying our statistical measures, we are able to identify a number of trends common to all three problems (which may represent intrinsic properties of the algorithm itself), as well as a host of problem-specific features. We find that the evolutionary algorithm tends to undergo a number of phases which we are able to quantitatively delimit. The results obtained lead us to believe that the measures presented herein may prove useful in the general case of analyzing fine-grained evolutionary algorithms.
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Personal studies in allergic eye diseases reviewed in this paper indicate that: 1. An increased number and an abnormal distribution of eosinophils is present in conjunctival biopsies of patients with vernal keratoconjunctivitis (VKC). 2. Eosinophil and eosinophil products, such as ECP, are also increased in tears of VKC patients and, in hay fever conjunctivitis, accumulate during the late-phase of allergic reaction following specific allergen challenge. 3. Circulating eosinophils of VKC patients show a typical activation phenotypic profile which is associated with increased serum level of eosinophil cationic protein and eosinophil-derived neurotoxin/protein X. A clinical study of the modulatory effect of cetirizine on the early and late phase of the allergic reaction as well as on the eosinophil activation and tissue recruitment following conjunctival allergen challenge is reported as an example of the need to evaluate eosinophil functions when investigating anti-allergic drugs. Drugs modulating various aspects of eosinophil function could play a primary role in the treatment of allergic eye disease.
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BACKGROUND: Eosinophil cationic protein (ECP) is a cytotoxic performed mediator stored in eosinophil granules and released under various in vitro and in vivo conditions. OBJECTIVE: This study was carried out to evaluate the clinical value of ECP as a marker of allergic inflammation. METHODS: ECP was measured by a competitive radioimmunoassay in serum samples from 265 patients and 45 matched control subjects and related to the type of allergic disease (asthma, rhinitis, conjunctivitis) and to the type of allergic sensitization. RESULTS: All the patient groups studied showed significantly higher levels of serum ECP than control groups (p < 0.001). The type of sensitization was shown to be the only variable influencing ECP serum levels. In fact, subjects sensitized to perennial allergens had significantly higher ECP values than subjects with seasonal allergy (p < 0.001), whereas in patients with seasonal allergy ECP levels were significantly increased only during the pollen season. Differences in ECP values between various allergic diseases or age groups were only due to a nonhomogeneous distribution of the type of sensitization or to time of sera collection. CONCLUSIONS: Results obtained indicate that persistent natural exposure to a sensitizing allergen is responsible for a measurable increase in serum ECP levels in patients with allergy.
PURPOSE: To evaluate whether the eosinophil preformed mediators, eosinophil cationic protein X, and eosinophil-derived neurotoxin/eosinophil protein X (EDN/EPX) are detectable in serum and can be used as markers of eosinophilic inflammation. METHODS: A competitive radioimmunoassay was used to detect serum levels of eosinophil cationic protein and EDN/EPX in 31 patients with vernal keratoconjunctivitis (VKC) and in 15 healthy controls. RESULTS: Mean serum levels of both eosinophil cationic protein and EDN/EPX were significantly higher in patients with VKC than in controls. There was a good correlation between serum levels of eosinophil cationic protein and EDN/EPX. No significant difference in mean serum eosinophil cationic protein levels was observed between patients with positive radioallergosorbent test (RAST) results and those with negative RAST results who have VKC, whereas mean EDN/EPX and total immunoglobulin E serum levels were significantly higher in patients with positive RAST results than in those with negative RAST results who have VKC. Serum eosinophil cationic protein, but not EDN/EPX, levels were significantly related to total immunoglobulin E levels. CONCLUSION: The authors' data indicate that serum levels of eosinophil cationic protein and EDN/EPX are useful markers of eosinophilic ocular inflammation in VKC.
The paper reviews personal studies aimed at identifying clinical markers of eosinophil inflammation in allergic diseases. Preliminary data on the use of flow cytometry as a method to detect eosinophil activation through phenotypic activation markers are reported. The concept of eosinophil releasibility is introduced on the basis of in vitro eosinophil activation and mediator release by different stimuli. Data showing an increase of serum levels of ECP mainly in subjects with sensitivity to perennial allergens and related to histamine bronchial reactivity are discussed in view of their practical impact in diagnosing and monitoring of allergic diseases and asthma.
To assess the significance of ST segment shift during the acute phase of non-Q myocardial infarction we studied the clinic echocardiographic, ergometric and coronarographic findings of 46 patients with a first non-Q wave myocardial infarction. The study population was subdivided in 2 subgroups on the basis of acute electrocardiographic change (Group I with ST elevation, Group II with ST depression). Patients with ST elevation had little myocardial infarction with enzymatic (early CPK peak) and coronarographic (low prevalence of coronary occlusion) signs of early spontaneous fibrinolysis. The second group had more diffuse myocardial infraction, higher prevalence of multivessel coronary disease and positive stress test. The ECG changes in this subgroup an probably due to subendocardial necrosis for the presence of collateral flow. The worse intrahospital prognosis of patients with ST segment depression may be related to cardiac function and age.
The haem enzyme myeloperoxidase (MPO) (EC 1.11.1.7) with a spectral A430/A280 ratio greater than 0.7 and a specific activity of 125 U/mg was purified from isolated human neutrophils. To obtain a radioimmunoassay (RIA) for this enzyme, a specific antiserum against human neutrophil MPO was raised in rabbits and used at an initial dilution of 1/10,000. MPO labelled with 125iodine by a technique of self-labelling in the presence of H2O2, had a specific activity of 24 mCi/mg. After incubation at room temperature (2 h) and separation by double antibody precipitation in the presence of polyethylene glycol, the sensitivity of the RIA was 21 ng/ml. The RIA showed good precision and accuracy with intra- and interassay coefficients of variation of less than 7% for MPO concentrations ranging from 100 to 800 ng/ml, and satisfactory recoveries of known amounts of exogenous MPO in plasma. For the measurement of MPO in blood, the best sampling technique was to collect blood into EDTA. Rapid centrifugation (within 20 min) was necessary for blood collected into heparin. Mean MPO values in normal individuals were 340 +/- 98 ng/ml in EDTA plasma (n = 152) and 332 +/- 82 ng/ml in heparinized plasma (n = 34). When MPO was measured 12-6 h after injury in critically ill patients high values (above 1000 ng/ml) were found in 6/15 patients with multiple injuries. In patients with sepsis (n = 22), MPO values were always above 1000 ng/ml.
The release of eosinophil peroxidase (EPO) and eosinophil cationic protein (ECP) was evaluated after incubation of eosinophils (EOSs) from allergic subjects with the specific allergen or with anti-IgE monoclonal antibodies (MAbs). High levels of EPO could be released after addition of the specific allergen (and not unrelated ones) or anti-IgE MAb. Moreover, EPO release with the two stimuli was significantly correlated both in allergic and in nonallergic patients. In the same supernatants, another granule protein, ECP, could not be detected, suggesting a lack of correlation between EPO and ECP release after IgE-dependent stimulation. However, when EOSs with surface-IgA antibodies were incubated with anti-IgA MAb, both EPO and ECP were released. In contrast, incubation of EOSs with anti-IgG MAb induced mainly the release of ECP and not EPO. These results indicate that pharmacologically active mediators can be released by EOSs from allergic and nonallergic patients on immunoglobulin-dependent activation. The results also confirm the hypothesis of a selective release of the various granule proteins and raise the question of transduction signals delivered by the three Fc receptors (Fc epsilon R, FC alpha R, and FC gamma R) present on human EOSs.
In hypereosinophilic patients, eosinophil heterogeneity has been assessed mainly according to morphologic and biologic criteria. In order to investigate the molecular basis of such heterogeneity, biochemical analysis was performed on various eosinophil subpopulations fractionated on metrizamide gradients. Whole cell extracts from purified eosinophils disrupted with a nonionic (NP-40) detergent were successively analyzed by SDS-PAGE and two-dimensional electrophoresis (isoelectric focusing or nonequilibrium pH gradient electrophoresis in the first dimension). Hypodense eosinophils that sediment in the lightest density gradients (18 to 22% metrizamide solution) differed from other purified eosinophils (intermediate and normodense eosinophils respectively collected in 22 to 23% and 23 to 25% metrizamide solutions). Comparative analysis of protein patterns on both monodimensional and bidimensional electrophoresis showed that a basic protein of Mr 51 kDa, present on normodense or intermediate eosinophils, was poorly detected in the case of hypodense eosinophils. In contrast, two other proteins with apparent Mr of about 23 kDa and 41 kDa were exclusively or predominantly identified in these latter cell fractions. Immunochemical analysis with polyclonal antibodies against eosinophil basic proteins and enzymatic assays revealed that the 51-kDa polypeptide could be related to an eosinophil peroxidase-like molecule. In addition, the two proteins detected only in hypodense eosinophils might be related to proteins newly synthesized by in vivo activated eosinophils. Our results suggest that variations in protein expression might represent a good marker of in vivo activation.
The presence of receptors for IgE on eosinophils has drawn the attention on their direct participation in IgE-dependent hypersensitivity reactions. Surface IgE antibodies were detected on eosinophils from allergic patients. The addition of the specific allergen or anti-IgE antibodies to such purified eosinophils induced the release of eosinophil peroxidase, but not of eosinophil cationic protein. These findings associated with results obtained by using electron microscopy and immunogold staining of the various antibodies directed against the granule proteins allowed us to suggest a selectivity in the mediators released by eosinophils. In addition, preliminary results concerning the existence and the functional role of a receptor for IgA on eosinophils are reported, leading to the concept of a particular interaction of eosinophils with immunoglobulins present in the tissues and their participation in local immune responses.
The clinical response after allergen challenge and immunologic mechanisms leading to tissue inflammation have been extensively studied in the skin, nose and lung of allergic subjects. The present paper reviews personal studies aimed at evaluating clinical, cellular and humoral events after administration of specific allergen to the eye. Specific conjunctival provocation tests performed in grass-sensitive patients caused persisting inflammatory changes in conjunctival scrapings and tear fluid with a significant accumulation of different inflammatory cells depending on the time of observation (neutrophils, 20 min; eosinophils, 6 h; neutrophils, eosinophils and lymphocytes, 12-24 h after provocation). Increasing the dose of allergen resulted in a dose-dependent increase in the number of inflammatory cells recruited. When high doses of allergen were used, the challenge not only induced late-phase histological changes, but also clinical symptoms 6-10 h after provocation. Several mediators of allergic inflammation, such as histamine, C3a des-Arg, leukotrienes B4 and C4, were also present and could be measured in tears after allergen challenge. Our studies represent the first evidence in humans that a late phase of allergic reaction occurs in the eye. They also suggest that the conjunctival provocation test may represent a model for the study of cells and mediators involved in the pathophysiology of allergic inflammation as well as of its pharmacologic modulation.
Cetirizine is a new anti-allergic compound with a potent, long-acting, and specific antihistaminic property. Strongly active in the therapy of urticaria and seasonal or perennial rhinitis, it has been shown to inhibit the in vivo eosinophil attraction at skin sites challenged with allergen in atopic patients. In the present work, we confirmed that, at a therapeutical concentration, this molecule had a potent inhibitory action in vitro on eosinophil chemotaxis induced either by N-formyl-Met-Leu-Phe or platelet-activating factor and also on the IgE-dependent stimulation of platelets. These observations appear in favour of a possible role for cetirizine in the modulation of inflammatory cell interactions in allergic processes.
The in vivo inhibitory effect of a new antiallergic, anti-H1 drug, cetirizine, on eosinophil attraction at skin sites challenged with various stimuli has been recently suggested. In the present work, we confirmed that this molecule, at therapeutical concentration, has a potent inhibitory action on eosinophil response to different chemoattractant mediators such as platelet-activating factor (PAF acether) and N-formyl methionyl leucyl phenyl alanyl in vitro. Another anti-H1 drug, polaramine, did not show this effect at the same concentration. These findings suggest that cetirizine in addition to its antihistaminic effect could also play a direct inhibitory effect on eosinophil recruitment. Moreover, cetirizine was not toxic for eosinophils and did not induce degranulation, as shown by the absence of peroxidase release. Comparison between cetirizine and a PAF acether antagonist (BN 52021) suggested that cetirizine did not act by a PAF receptor-blocking activity.
The existence of receptors for immunoglobulin A on human eosinophils is demonstrated by flow cytofluorometry. Between 5 and 60% of eosinophils purified from peripheral blood of hypereosinophilic patients are able to bind monomeric serum IgA. The addition of antihuman IgA antibodies to surface IgA-bearing eosinophils induces the exocytosis of peroxidase contained in the granules suggesting a cell activation due to IgA receptors. The inhibition of antiparasitic cytotoxicity by eosinophils preincubated with IgA under a polymeric form only, indicates the low affinity of IgA receptors as well as their participation in the effector function of eosinophils.