Search PubMed⌕ Search

Biomedical subjects

P Paoletti

Publications and source records attributed to P Paoletti.

At least 37 records · Page 2Linked to original sources
PubMed1996

Importance of baseline cotinine plasma values in smoking cessation: results from a double-blind study with nicotine patch.

Nicotine replacement by transdermal patches is more effective than placebo in smoking cessation, but has a low success rate after one year (9-18%). We tested whether this was attributed to insufficient nicotine replacement. We conducted a randomized trial to investigate the effect on outcome of different doses of transdermal nicotine replacement after stratification according to baseline plasma cotinine values. Two hundred and ninety seven adult smokers were enrolled. Those with baseline cotinine < or = 250 ng.ml-1 (low cotinine) were randomly assigned to placebo (LC-P) or to 15 mg 16 h nicotine patches (LC-15), and those with baseline cotinine > 250 ng.mL-1 (high cotinine) were randomly assigned to 15 mg (HC-15) or 25 mg (HC-25) 16 h nicotine patches. Plasma nicotine and cotinine values, expired carbon monoxide and withdrawal symptoms were measured at scheduled intervals during treatment. Smokers in the LC-15 group had a significantly higher success rate than placebo (28 vs 9%). Smokers with high baseline cotinine had lower success rates, and a high dose of nicotine did not increase success rate (HC-25 9% vs HC-15 11%). Subjects in the HC-15 group had the lowest percentage of nicotine replacement and a higher prevalence of withdrawal symptoms than the HC-25 group. Replacement was similar in groups LC-15 and HC-25, but the success rate was significantly lower in HC-25 group, despite similar levels of withdrawal symptoms. We conclude that a higher success rate was obtained after one year in smokers with low baseline plasma cotinine values. Determination of plasma cotinine values may be, thus, helpful in identifying smokers who could benefit from transdermal nicotine replacement.

Adult↗
PubMed1995

Application of biomarkers in population studies for respiratory non-malignant diseases.

Though the use of biomarkers has been mainly suggested for cancer studies, the possibility of its use in non malignant disease is considered. Markers of internal dose, markers of biologically effective dose and markers of early biologically effect have been typically used in basic research and, more recently, in epidemiology to characterize genotoxic carcinogenic agents. These markers (e.g. adducts to DNA or proteins) may be used mainly in the presence of chronic exposure to toxic agents (e.g. benzene or benzopyrene), additional markers such as carboxyhemoglobin, expired air to measure various VOC and heavy metals in biological fluids are also considered in the paper. Since airway obstructive disease (asthma, chronic bronchitis, emphysema) are the main disorders influenced by environmental factors (including air pollution), markers of individual susceptibility, such as atopy increased responsiveness of airways, initial level of lung function, must be considered for a more precise evaluation of the relationship between environmental exposure and health effects. Currently, the application of the determination of markers of exposure in non malignant disorders is very limited. In fact, the relationships between acute adverse respiratory effects and the exposure to air pollutants appears difficult since markers for common air pollutants are not available, and their detection appears difficult in acute conditions. Characterization of long term exposure may be performed in organ fluids (blood, urine, saliva) however it is important to recognize that concentration at that level may not reflect that observed in the target organ (e.g. lung).

Air Pollutants↗
PubMed1995

Spirometric reference values for white European children and adolescents: Polgar revisited.

We analyzed six spirometric data sets collected in the Netherlands, Austria, the United Kingdom, Spain, and Italy. The objectives were to establish whether (1) it was possible to describe spirometric indices from childhood to adulthood, taking into account the adolescent growth spurt, and (2) there are systematic differences in ventilatory function between children and adolescents in different parts of Western Europe. The study comprised 2,269 girls and 3,592 boys, aged 6-21 years. The range in standing height was 110-185 in girls, 110-205 in boys. The model applicable to all data sets was ln FVC or ln FEV1 = a + (b + c x A) x H, where H = standing height and A = age; this model prevents the phase shift between the adolescent growth spurt in length and lung volume from leading to an age-dependent bias in predicted values. There was surprising agreement between most of the data sets; systematic differences are probably due to technical factors arising from ATPS-BTPS corrections and from defining the end of breath with pneumotachometer systems. Taking those into account, prediction equations for FVC, FEV1, and FEV1%FVC were developed with "lower limits of normal" which should be applicable to children and adolescents of European descent. It is proposed that the approach of analyzing available data sets should also be applied to other ventilatory indices, data collected in adults and elderly subjects, or in other ethnic groups, and that an international data base be set up to that end.

Adolescent↗
PubMed1995

Glycine-independent and subunit-specific potentiation of NMDA responses by extracellular Mg2+.

Extracellular Mg2+, which blocks NMDA channels in a voltage-dependent manner and increases the receptor's affinity for glycine, is shown here to potentiate NMDA responses at saturating glycine concentrations. This potentiation, induced by millimolar concentrations of Mg2+, is not mimicked by Ca2+ and Ba2+ and is voltage independent. The potentiation is variable in native receptors of cultured mouse central neurons; in recombinant receptors, it is "permitted" by the NR2B subunit and prevented by the NR1 splice variant containing an N-terminal insert. Mg2+ also induces a shift of the pH sensitivity of NMDA receptors. The similarity and nonadditivity of the effects of Mg2+ and spermine suggest that Mg2+ may be the physiological agonist acting at the subunit-specific spermine site.

Animals↗
PubMed1995

Plasma endothelin and renal endothelin are two distinct systems involved in volume homeostasis.

This study of seven healthy young subjects was designed both to establish whether endothelin-1 (ET-1) is involved in the homeostasis of blood volume and to clarify the relationship between plasma and urinary ET-1. Acute volume expansion (+17%) caused increases in venous blood pressure (+4.4 mmHg) and the plasma concentration of ET-1 (+129%) and a decrease (-99%) in the urinary excretion of ET-1. Volume depletion (-8.5%) provoked an increase in the plasma concentration of ET-1 without altering the urinary excretion of ET-1. Passive elevation of an arm resulting in a local decrease of venous blood pressure (-17 mmHg) elicited an increase of the local formation of ET-1, with a 10-fold increase in the venous-arterial gradient compared with the opposite arm, which lay at the level of the heart. The increased local formation of ET-1 was blunted by volume expansion. The results indicate that 1) plasma ET-1 and urinary ET-1 represent two different endothelin-generating systems, both of which are involved in the regulation of blood volume, and 2) plasma ET-1 appears to be an important mechanism for the long-lasting adaptations of venous wall tension to changes in blood volume.

Adult↗
PubMed1995

Distribution of bronchial responsiveness in a general population: effect of sex, age, smoking, and level of pulmonary function.

Bronchial responsiveness (BR) was assessed by the methacholine challenge test in 1,694 subjects from a sample of the general population (aged 8 to 73 yr) enrolled in a prospective epidemiologic study on the natural history of chronic obstructive pulmonary disease (COPD). Information on respiratory symptoms and risk factors for COPD were obtained with a standardized questionnaire. The provocative dose causing a 10%, 15%, and 20% decrease in FEV1 was reached in 939 (55%), 658 (39%), and 447 (26%) subjects, respectively, after the last cumulative dose of methacholine (i.e., 4.8 mg). The slope of the dose-response curve was also computed in order to attribute a parameter to subjects who did not reach the provocative dose. After natural log transformation, the slope (Ln Slope) of the curve showed a significant association with the degree of airway obstruction, as assessed by FEV1% predicted, FEV1/VC%, and FEV1/FVC%. Therefore, relationships between BR, sex, age, and smoking were evaluated after adjustments for the initial airway caliber (FEV1, FEV1 adjusted for height, and FEV1/VC%). Females showed significantly higher values of Ln Slope than did males after adjustments were made for baseline lung function. In males, higher BR was observed in childhood-adolescence age groups and at older ages, while in females a higher level of BR was observed during childhood. Significantly higher Ln Slope values were found for females who currently smoked than for non- and ex-smokers. No difference was observed in males in relation to smoking habit. (ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Risk factors for chronic obstructive pulmonary disease in a north Italian rural area.

To assess the role of risk factors for chronic obstructive lung disease (COPD) by multiple logistic models, the data of the first cross-sectional epidemiological survey in the unpolluted rural area of the Po River Delta were analyzed (n = 2382; 20-64 years). Each subject filled out a standardized questionnaire; 94% of the subjects were also able to perform forced expirograms. Dependent variables were chronic respiratory symptoms, asthma, abnormal parameters of flow-volume curve (ABNFVC), and a complex characterized by chronic phlegm, and/or any wheeze and/or dyspnea grade 2+ and/or diagnosis of asthma and/or an FEV1/FVC ratio less than 60% (ANYABN). Independent variables were: age, ever cigarette smoking (SMK) and lifetime cigarette consumption expressed as pack-years, childhood respiratory infections (CRI), adolescence-adulthood respiratory infections (ARI), familial history for COPD (FCOPD) or for asthma/allergies (FASTHMA), work exposure to dusts/chemicals (EXPO), low socio-economic conditions (SES). A significant relationship with almost all dependent variables was shown by pack-years, ARI and age in both sexes. In males, FCOPD was related to chronic mucus hypersecretion and to ABNFVC, FASTHMA was associated with wheeze and ANYABN. EXPO was related to dyspnea and asthmatic symptoms in both sexes and also to bronchitic symptoms in males. CRI was a significant contributor for asthma symptoms in males, for ANYABN in females. SES had no significant association. In conclusion, our findings show that, beside lifetime cigarette smoking, other host--or environment--related conditions are important risk factors for COPD, suggesting the need for a more thorough strategy for prevention.

Adolescent↗
PubMed1994

Mechanosensitivity of NMDA receptors in cultured mouse central neurons.

Changes in osmotic and hydrostatic pressure were found to modulate NMDA responses of cultured embryonic mouse neurons recorded in various patch-clamp configurations. In nucleated patches, NMDA currents were potentiated by reductions in external osmolarity and were reduced in hyper-osmotic solutions. These changes, which were greater for low concentrations of NMDA, were not observed for responses to kainate, glycine, or GABA. They could be mimicked by directly changing the pipette pressure in nucleated, outside-out, inside-out, and cell-attached patches. Osmosensitivity of NMDA responses was also observed in the whole-cell mode, but only after prolonged dialysis. Mechanosensitivity of NMDA receptors could have an important role in neuronal regions experiencing changes in membrane tension, such as spines or growth cones.

Animals↗
PubMed1994

Endothelin and aneurysmal subarachnoid haemorrhage: a study of subarachnoid cisternal cerebrospinal fluid.

Endothelin (ET) is considered one of the most potent vasoconstrictor polypeptides; several experimental studies have suggested its possible role in the pathogenesis of arterial vasospasm after subarachnoid haemorrhage (SAH). Previously reported data on plasma and CSF levels of endothelin in patients with a diagnosis of SAH have been controversial. Cisternal endothelin CSF levels and the possibility that they could be related to vasospasm and other clinical patterns of SAH were investigated. CSF samples were obtained from 55 patients admitted after angiographic diagnosis of intracranial aneurysm. Levels of ET-1 and ET-3 were measured through radio-immunoassay technique. Twelve patients who had operations for unruptured aneurysms were considered control cases; 43 patients with SAH were classified according to: Hunt and Hess grading at admission, vasospasm grading, CT classification and timing of surgery. In all 55 patients ET-1 was measured, while positive levels of ET-3 were found only in 17 cases of 48. No linear correlation was found between cisternal CSF ET-1 levels when considering time of surgery, CT classification, Hunt and Hess grading at admission, and vasospasm grading. The results of ET-3 assay should be considered with great caution because of the low percentage of positive cases. Cisternal CSF levels of ET-1 and ET-3 are not directly related to the occurrence of arterial vasospasm after the aneurysm rupture, or to other major clinical patterns of SAH; however, ET-1 expression occurs either in paraphysiological (unruptured aneurysm) or in pathological conditions (SAH). It is suggested that ET may potentiate, or may be potentiated by, other factors playing a consistent pathophysiological role in the development of vasospasm.

Brain Diseases↗
PubMed1994

[An unusual case of pulmonary infiltrates with hepatic involvement in a woman with eosinophilia].

The literature reports many cases of eosinophilic pulmonary infiltrations, with different etiology. In our case clinical pictures were not very clear and specific at first and the clinical course was altered by an ex adjuvantibus steroid treatment before admission to hospital. It was new and unusual because it presented some characteristics of chronic eosinophilic pneumonia and idiopathic hypereosinophilic syndrome, with hepatic involvement as in the former, but without serious heart disease as in the latter. This confirms the difficulties in making a classification of the different clinical pictures because of their indistinct margins, which might appear as different forms of a single disease. In our case the patient refused transbronchial lung biopsy which is commonly considered a minimum diagnostic requirement. Some authors are not in agreement and think it is sufficient to find eosinophils in BAL to start steroid treatment, avoiding biopsy risks. Another interesting finding is the need for a long-term low-dose steroid treatment, to avoid relapses.

Female↗
PubMed1994

Prevalence rates of diagnosis of asthma in general population samples of northern and central Italy.

In order to assess the distribution of asthma in Italy in the 1980s, we have compared the findings of three general population surveys carried out in the North and the Centre of the country. Two cross-sectional investigations were performed in the Po Delta area (North Italy), 6 yrs apart: 1) 3,285 subjects, aged 8-64 yrs, in 1980-1982 (PD1); and 2) 2,841 subjects, aged 8-73 yrs, in 1988-1991 (PD2). One cross-sectional survey was carried out in Pisa (Central Italy): 3,866 subjects, aged 5-90 yrs, in 1985-1988 (PI1). For this analysis we have used data from the standardized questionnaires of those subjects between 18-64 yrs, who were currently employed. The prevalence rate of ever asthma was 3.3-5.5%, that of current asthma 1.3-2.9%; almost all of the diagnoses were confirmed by a doctor. Taking into account only doctor-confirmed asthma, the age of onset of manifestations was most frequently over 18 yrs (41-79%). It also occurred more frequently after the onset of employment. As regards smoking, whilst most asthmatic males were current or former smokers (70-86%), most asthmatic females were nonsmokers. However, the situation changed in PD2, where females showed the same pattern as males. Considering asthmatic subjects with skin-prick test reactivity (data available only in PD2), the vast majority (67% in males, 75% in females) had an age of disease onset under 18 yrs. In conclusion, the prevalence of asthma in Italy in the 1980s was similar to that in other European countries and was affected by atopy and smoking differently in the two sexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Bronchial reactivity in a general population of north Italy: relationships with occupational exposure.

Two thousand eight hundred and forty one subjects, aged 8-73 yrs, took part in the second cross-sectional survey in the Po River Delta area: among them, a subsample of currently employed people, aged 14-71 yrs, was chosen to establish the relationship between occupational exposure to dusts, chemicals or gases and respiratory symptoms, lung function and bronchial reactivity. Each subject filled out the Italian National Research Council (CNR) standardized questionnaire concerning respiratory symptoms, diseases and risk factors. A variable proportion of subjects performed acceptable forced and slow vital capacity manoeuvres, diffusing capacity of carbon monoxide and bronchial challenge test to methacholine. Occupational exposure appeared to be related to prevalence rate of respiratory symptoms (wheeze, dyspnoea, presence of at least one respiratory symptom) and bronchial asthma. Consistent effects on lung function were not evident. With respect to the bronchial challenge test, using the measurement of the provocative dose producing a 20% fall in forced expiratory volume in one second (PD20) a significantly higher percentage of hyperreactive subjects was found among ex-smoker exposed men; a borderline higher percentage of hyperreactive subjects was also found in non-smoker exposed women. The study findings support the suggestion that occupational exposure may play a role in the development of airway obstructive diseases.

Adolescent↗
PubMed1993

Macrophage-specific eicosanoid synthesis inhibition and lipocortin-1 induction by glucocorticoids.

It has been suggested that the induction of lipocortin-1, a phospholipase A2-inhibitory protein, may mediate the anti-inflammatory action of glucocorticoids. We assessed the production of prostaglandin E2, thromboxane B2, and leukotriene B4 and the expression of lipocortin-1 in different populations of blood leukocytes and in alveolar macrophages (obtained by bronchoalveolar lavage) from patients with inflammatory lung diseases (bronchial asthma, n = 21; interstitial lung disease, n = 6) undergoing glucocorticoid treatment at clinically effective doses. No inhibition of eicosanoid production was observed in either whole blood or single populations of blood leukocytes (granulocytes and monocytes) stimulated with ionophore A-23187, N-formyl-L-methionyl-L-leucyl-L-phenylalanine, or zymosan. Conversely, eicosanoid production from alveolar macrophages (assessed in 9 cases) was significantly inhibited by glucocorticoids. After ionophore stimulation, eicosanoid production was as follows (in ng/ml): prostaglandin E2, 0.19 +/- 0.06 and 0.06 +/- 0.01; thromboxane B2, 2.9 +/- 0.9 and 0.5 +/- 0.1; leukotriene B4, 6.6 +/- 1.1 and 3.6 +/- 1.0, before and after treatment, respectively (P < 0.05 for all differences). Lipocortin-1 expression, determined by Western blot and enzyme immunoassay, was significantly (P < 0.05) stimulated in alveolar macrophages, but not in blood leukocytes, by glucocorticoid treatment. These results indicate that alveolar macrophages, at variance from blood leukocytes, are the most likely cell target for glucocorticoid-induced eicosanoid inhibition and lipocortin expression. We suggest that cell responsiveness to glucocorticoids is acquired during differentiation from monocyte to tissue macrophage.

Adolescent↗
PubMed1993

CO diffusing capacity in a general population sample: relationships with cigarette smoking and airflow obstruction.

The single-breath carbon monoxide diffusing capacity (DLCOsb) was measured together with ventilatory lung function tests as part of a survey of a general population sample living in Northern Italy (n = 2,481). Based on answers to an interviewer-administered questionnaire, subjects free of respiratory symptoms or diseases were identified. Data from subjects who had never regularly smoked cigarettes were used to derive reference equations for the test indexes, and data from the remaining subjects who had smoked were used to derive regression equations incorporating a term expressing cigarette consumption (cube root of pack-years) and a term indicating current smoking decrement, in order to obtain expected DLCOsb percent predicted. Neither number of cigarettes smoked daily or duration of smoking, in smokers, nor duration of smoking or years since quitting smoking, in ex-smokers, entered significantly the multiple-regression model. The mean values of DLCOsb were only slightly affected by the increasing degree of airway obstruction. When subjects with confirmed asthma were analyzed, after stratifying for different levels of FEV1/FVC ratio, increased mean value of DLCOsb (over 100%) was found in those with an FEV1/FVC ratio between 75 and 65%. This cross-sectional analysis suggests that there is a decrease in DLCOsb with cumulative cigarette consumption even in healthy subjects. Further, it confirms the clinical observations of high DLCOsb values in asthmatic patients, at least in those with an initial degree of chronic airflow obstruction.

Adolescent↗
PubMed1993

Serum levels of soluble interleukin-2 receptor in patients with systemic lupus erythematosus and systemic idiopathic vasculitis.

Soluble interleukin 2 receptor (sIL2R) may be used as an index of immune perturbation. We report on the correlation between the serum levels of sIL2R, as assessed with a sandwich-ELISA, and disease activity in 61 patients with Systemic Lupus Erythematosus (SLE) and in 15 with systemic idiopathic vasculitis (SIV). The mean levels of sIL2R in SLE and SIV patients were significantly higher than in healthy controls and higher values were detected in patients with active disease or severe organ involvement or infection. We also studied patients with clinically silent SLE, characterized by the presence of several immunologic abnormalities. The sIL2R mean level in this group did not differ from that of quiescent SLE patients, suggesting that immunologic alterations are present even in inactive SLE. Finally, the sIL2R assay showed higher sensitivity and specificity than most of the common immunologic parameters.

Adolescent↗