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Biomedical subjects

G Melillo

Publications and source records attributed to G Melillo.

At least 19 recordsLinked to original sources
PubMed1992

Tumor necrosis factor-alpha-dependent production of reactive nitrogen intermediates mediates IFN-gamma plus IL-2-induced murine macrophage tumoricidal activity.

We have previously established that IFN-gamma plus IL-2 induces murine macrophage tumoricidal activity. The purpose of this study was to identify the effector molecules that account for the IFN-gamma plus IL-2-induced macrophage cytotoxicity against P815 mastocytoma cells. ANA-1 macrophages and normal thioglycollate-elicited mouse peritoneal macrophages produced little or no detectable nitrite (NO2-) after incubation with IFN-gamma alone or IL-2 alone; however, IL-2 synergized with IFN-gamma for the production of NO2-. IFN-gamma plus IL-2 did not induce NO2- production or tumoricidal activity in ANA-1 macrophages that were cultured in medium devoid of L-arginine or in ANA-1 macrophages that were incubated with NG-monomethyl-L-arginine. As observed previously with ANA-1 macrophage tumoricidal activity, IL-4 inhibited IFN-gamma plus IL-2-induced, but not IFN-gamma plus LPS-induced, NO2- production. IL-4 also selectively decreased the ability of IFN-gamma and/or IL-2 to augment TNF-alpha mRNA expression in ANA-1 macrophages. Lastly, incubation of ANA-1 macrophages with anti-TNF mAb selectively inhibited the ability of IFN-gamma plus IL-2 to induce NO2- production and tumoricidal activity. These results indicate that IFN-gamma plus IL-2-induced tumoricidal activity is dependent upon the metabolism of L-arginine to reactive nitrogen intermediates, and they establish a role for TNF-alpha as a required intermediate for IL-2-dependent NO2- production and tumoricidal activity.

Animals↗
PubMed1992

Peripheral site of action of levodropropizine in experimentally-induced cough: role of sensory neuropeptides.

The mechanism of action of levodropropizine has been investigated in different models of experimentally-induced cough in guinea-pigs. In particular it has been demonstrated that the antitussive drug has a peripheral site of action by injecting the drug intracerebroventricularly (i.c.v.). In these experiments levodropropizine (40 micrograms/50 microliters i.c.v.) did not prevent electrically-induced cough. On the other hand, codeine (5 micrograms/50 microliters i.c.v.) markedly prevented coughing. A difference in the potency ratio of levodropropizine and codeine has been demonstrated in capsaicin-induced cough; after oral administration, codeine was about two to three times more potent than levodropropizine. However, after aerosol administration the two compounds were equipotent. These data might suggest a peripheral site of action for levodropropizine which is related to sensory neuropeptides. Further support for the role of sensory neuropeptides in the mechanism of action of levodropropizine comes from the results obtained in capsaicin-desensitized animals. In this experimental model levodropropizine failed to prevent the vagally elicited cough in neuropeptide-depleted animals, whereas codeine did not differentiate between control and capsaicin-treated animals. In conclusion, our results support the suggestion that levodropropizine has a peripheral site of action. In addition, the interference with the sensory neuropeptide system may explain, at least in part, its activity in experimentally-induced cough.

Animals↗
PubMed1991

Clinical magnetocardiography. 10 years experience at the Catholic University.

Since the introduction, in 1982, of a Biomagnetic facility in the clinical environment, efforts were concentrated to investigate whether magnetocardiography could really provide new information of potential diagnostic use, even avoiding electromagnetic shielding to facilitate simultaneous biomagnetic and conventional cardiac investigations, including cardiac catheterization for invasive electrophysiological procedures. More than 350 patients have been magnetically investigated using a single-channel second-order gradiometer. Results of 281 MCG studies, whose data have been extensively analyzed with updated software programs, are reported. Magnetocardiographic (MCG) mapping during endocardial pacing was performed to quantify the accuracy of MCG localization of intracardiac dipolar sources. MCG classification of ventricular preexcitation has been attempted in 70 patients with overt preexcitation. MCG localization of the ventricular preexcited area was accurate and reproducible, provided that during mapping a sufficient degree of ventricular preexcitation was present. MCG mapping during orthodromic A-V re-entry tachycardia has been also employed to attempt the localization of retrograde atrial preexcitation as well as the site of origin of atrial and ventricular tachyarrhythmias. For validation, the results of catheter and epicardial mappings have been used. Other applications of clinical magnetocardiography are under evaluation. The use of the Relative smoothness index needs, in our opinion, a larger experience to define its reliability as a predictor of risk for sudden death. MCG follow-up study of patients with transplanted hearts seems to be a promising application, for early detection of acute graft rejection reaction. Our reported case strongly supports this potentiality. Present work is also addressed to develop an integrated system allowing easy MCG mapping during cardiac catheterization, as a new method to guide diagnostic and therapeutic procedures as close as possible to the arrhythmogenic substrate.

Electrocardiography↗
PubMed1991

Biomagnetically localizable multipurpose catheter and method for MCG guided intracardiac electrophysiology, biopsy and ablation of cardiac arrhythmias.

A multipurpose catheter, specially designed to be biomagnetically localizable and the method for magnetocardiographic (MCG) guided intracardiac electrophysiological recordings, endomyocardial biopsy and ablation of cardiac arrhythmias are described. The catheter features two non-polarizable non-ferrous magnetic electrodes, arranged in such a way that, connected to an external current generator, an electromagnetic field of dipolar configuration can be generated in the heart. The connection is done with twisted pairs of non-ferrous magnetic conductors, to avoid the occurrence of spurious magnetic fields along the catheter during current injection to the electrodes. With this assembly the tip of the catheter can be localized (and driven close to an arrhythmogenic area) by MCG mapping. The same electrodes are feasible for monophasic action potential (MAP) recordings. One or more lumen allow fluid infusion, blood sampling, pressure measurements and introduction of steerable wires, pacing or ablation electrodes, bioptic devices, or optic fibers. On the basis of preoperative MCG three-dimensional localization of the arrhythmogenic substrate, the biomagnetically localizable catheter is driven, under fluoroscopic control, as close as possible to the suspected arrhythmogenic zone. MCG mapping is then performed under pacing, with adjustments of the catheter's tip, until the electrically induced magnetic field and catheter's localization parameters fit those generated by the spontaneous arrhythmia. MAP is recorded. The catheter position is accepted for ablation when electrophysiological abnormalities are identified in the MCG localized area.

Action Potentials↗
PubMed1991

Biomagnetic study of cardiac arrhythmias.

Clinical magnetocardiographic mapping was initiated in the Cardiovascular Biomagnetism Unit of the Catholic University of Rome about 10 years ago. Since then several hundred patients have been investigated. However, the most interesting data have been collected after the development, in 1984, of the present laboratory configuration, which allows simultaneous MCG mapping and invasive electrophysiological procedures. Perspective studies have been carried out to validate the accuracy of MCG for localisation of arrhythmogenic structures and for early detection of patients at risk of sudden death. Although the diagnostic applicability of the method is still under evaluation, preliminary results are reported, concerning 120 patients, investigated between 1985 and 1990, with cardiac arrhythmias associated with ventricular pre-excitation, ischaemic heart disease or cardiomyopathies.

Arrhythmias, Cardiac↗
PubMed1991

Aspirin-induced asthma and bronchial hyperresponsiveness.

The inhalation challenge with lysine-aspirin (L-ASA) using the dosimeter method allows the construction of a dose-response curve and the quantitative estimation of airway responsiveness to the drug. We assessed the modifications of airway responsiveness to methacholine in four groups of subjects: aspirin-sensitive asthmatics, aspirin-sensitive subjects with urticaria/angioedema, subjects with an equivocal history of aspirin intolerance and normal control subjects. The L-ASA challenge was positive in all aspirin-sensitive asthmatics. The pattern of bronchial response to the challenge was different from that observed after challenge with allergens or occupational sensitizers. The main difference was found in the recovery from induced bronchoconstriction. The recovery lasted from 3 to 6-8 hours, and a peculiar dose-response curve was obtained that we call "early prolonged reaction". In five of 18 ASA-sensitive subjects there was a significant increase in airway responsiveness. Airway responsiveness was normal in aspirin-sensitive nonasthmatic subjects and in the other two groups studied. We conclude that L-ASA inhalation challenge may increase bronchial hyperresponsiveness in some ASA-sensitive asthmatics. This presence of enhanced bronchial hyperesponsiveness seems to be a marker with which to distinguish ASA-sensitive asthmatics from ASA-sensitive subjects with urticaria/angioedema.

Adolescent↗
PubMed1989

Human basophil/mast cell releasability. V. Functional comparisons of cells obtained from peripheral blood, lung parenchyma, and bronchoalveolar lavage in asthmatics.

Releasability of human basophils and mast cells is an important parameter in allergic disorders. We compared IgE- and non-IgE-mediated releasability of human peripheral blood basophils with that of mast cells obtained from lung parenchyma (isolated by mechanical or enzymatic dissociation) and from bronchoalveolar lavage of normal and asthmatic donors. In a first study, the response to anti-IgE, Staph A, Con A, f-met peptide, and Ca2+ ionophore A23187 of basophils obtained from 52 donors was compared with that of mast cells isolated enzymatically (PMCE) or mechanically (PMCM) from lung parenchyma obtained during surgery. The histamine content of basophils (1.1 +/- 0.1 pg/cell) was significantly lower than that of PMCE (4.1 +/- 0.3 pg/cell; p less than 0.001) and PMCM (3.7 +/- 0.3; p less than 0.001). The maximal percent anti-IgE-induced histamine secretion in basophils (41.3 +/- 3.6) was higher than in PMCE (17.5 +/- 1.8) and in PMCM (13.8 +/- 1.5). Similarly, the response to Staph A and Con A was higher in basophils (29 +/- 3.9 and 31.6 +/- 4.9, respectively) than in PMCE (3.5 +/- 0.6 and 3.3 +/- 0.8, respectively) and PMCM (5.1 +/- 1.3 and 8.8 +/- 2.2, respectively). A positive correlation between the maximal percent of histamine release induced by anti-IgE and Staph A was found in basophils (rs = 0.61; p less than 0.001), whereas there was a negative correlation between the reactivity of PMCE (rs = 0.67; p less than 0.001) and PMCM (rs = -0.40; p less than 0.001) to anti-IgE and their reactivity to Staph A.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Intrasubject between-day variability of PD20 methacholine assessed by the dosimeter inhalation test.

The intrasubject between-day variability of the methacholine inhalation test (MIT) was estimated in a group of 30 patients (15 males, mean age 29 yr), representative of a wide range of degrees of nonspecific bronchial responsiveness (from normal to severely increased). In each patient, an MIT with the dosimeter method was carried out on three separate occasions within one week, keeping as constant as possible both the technical and patient-related factors (FEV1 within +/- 5 percent, no recent airway inflammation) and independently from operator-related factors (three tests, three different operators blinded with regard to previous MIT results). On each occasion, twofold increasing doses of methacholine were given from 6.25 to 3,200 micrograms as cumulative doses, at five-minute intervals by means of a dosimeter Me.far MB3 (nebulization time 0.8 +/- 0.2s, output 5 +/- 0.2 microliters/puff). The FEV1 was measured initially and 1.5 and 3 minutes after each inhalation. The test was continued until either a fall of 20 percent or more in FEV1 was obtained or the last dose was reached. The results were expressed in terms of PD20, ie, the dose of methacholine producing a 20 percent fall in FEV1. Under these carefully controlled conditions, the 95 percent confidence intervals (as based on a single determination) corresponded to +/- 0.22 on a log10 scale or, in a more meaningful way, +/- 1.66 fold-difference in PD20 from one visit to the other.

Adolescent↗
PubMed1989

Prolonged treatment with acrivastine for seasonal allergic rhinitis.

In a double-blind, placebo-controlled multicentre study, the antihistamine acrivastine, was used over prolonged periods for the treatment of seasonal allergic rhinitis. After the initial treatment period of 10 days, 8 mg acrivastine three times daily was significantly superior to placebo in controlling the symptoms of sneezing, itchy nose, running nose, watery eyes, itchy eyes and itchy throat. The benefit from acrivastine was also apparent in the second (14 days) and third (28 days) treatment periods, although the difference no longer reached statistical significance. This was probably due to the large proportion of non-responders in the placebo group who withdrew from the study owing to lack of efficacy. The investigators rated symptom control with acrivastine to be 'good' in comparison to 'poor' control with placebo treatment (P = 0.01) for all three periods. There were no significant differences between acrivastine and placebo in the incidence of adverse experiences at the end of each treatment period. Acrivastine is effective and well tolerated over prolonged periods (up to 52 days) for the treatment of seasonal allergic rhinitis.

Adult↗
PubMed1989

Treatment of reversible chronic airways obstruction with doxofylline compared with slow-release theophylline: a double-blind, randomized, multicentre trial.

A multicentre, double-blind, randomized trial was carried out in 11 Italian Pneumologic Clinics to investigate the therapeutic efficacy and tolerability of doxofylline compared with slow-release theophylline in 139 patients (86 males, 53 females) aged 17-77 years suffering from reversible chronic airways obstruction. The two groups of 69 patients on doxofylline and 70 patients on theophylline did not differ in their baseline clinical and functional parameters. After one week of wash-out, the two drugs were administered orally at a dose of 400 mg twice daily of doxofylline and 300 mg twice daily of theophylline. The treatment and follow-up lasted 28 days. Inhaled salbutamol on demand was allowed in the wash-out week and throughout the trial. The average serum levels at day 14 and 28 were: doxofylline 7.5 and 8.5 micrograms/ml; theophylline 10.4 and 7.95 micrograms/ml respectively. Both drugs significantly increased spirometric parameters (p less than 0.001 for all tests) and significantly reduced salbutamol consumption (p less than 0.001 for both drugs). Doxofylline was better tolerated than theophylline considering either the number of unwanted side-effects: (doxofylline 12; theophylline 37) or number of drop-outs due to side-effects (doxofylline 5; theophylline 10). From these results doxofylline seemed to be a good alternative to theophylline in the treatment of reversible chronic airway obstruction in view of its better safety profile.

Adolescent↗