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Biomedical subjects

G Bonsignore

Publications and source records attributed to G Bonsignore.

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

Evaluation of diaphragmatic fatigue in obstructive sleep apnoeas during non-REM sleep.

BACKGROUND: Resistive load applied to the airways may induce diaphragmatic fatigue, and hypoxaemia has been shown to predispose to the development of fatigue. Inspiratory muscle fatigue may occur in patients with obstructive sleep apnoea syndrome (OSAS), as these patients repetitively develop both inspiratory loading and hypoxaemia. The results of previous studies on this topic are inconclusive, probably because of the methodological approaches used. METHODS: Six obese patients with OSAS underwent a polysomnographic study. The diaphragmatic pressure time index (PTI) was evaluated as an indicator of diaphragmatic contraction, and the mean frequency of the diaphragmatic electromyogram power spectrum (Fm) and the maximum relaxation rate of transdiaphragmatic pressure (MRR) as indices of a fatiguing diaphragm. A total of 119 randomly selected apnoeas (each including 5-13 occluded efforts) were analysed throughout the night in non-REM sleep to assess possible muscle fatigue due to the high pressure generation in each apnoea. A breath-by-breath within-apnoea analysis was performed on the first three pre-apnoeic breaths, on all the occluded efforts, and on the first three unoccluded breaths following the apnoea interruption. Possible fatigue development due to the cumulative effect of apnoeas over the night was also evaluated. RESULTS: A progressive increase of Fm and MRR was found during the obstructive phase in all the subjects in the within-apnoea analysis. The overnight analysis did not show a reduction in either PTI, Fm, or MRR secondary to recurrent upper airway obstruction during the night. CONCLUSIONS: No evidence of diaphragmatic fatigue or impaired diaphragmatic contraction was found either within each apnoea or throughout the whole night, despite the generation of high PTI values during the apnoeic occluded phases. It is concluded that diaphragmatic fatigue does not occur in OSAS during non-REM sleep.

Adult↗
PubMed1997

Transforming growth factor-beta expression in mucosal biopsies in asthma and chronic bronchitis.

We assessed whether transforming growth factor-beta (TGF-beta), a fibrogenic growth factor, may be involved in remodeling of asthma and chronic bronchitis; its expression was compared with that of epidermal growth factor (EGF) and granulocyte macrophage colony-stimulating factor (GM-CSF) in bronchial mucosal biopsies from 13 normal subjects, 24 asthmatics, and 19 patients with chronic bronchitis. TGF-beta immunoreactivity was highly increased in epithelium and submucosa of those with bronchitis and to a lesser extent in asthmatics. By comparison, with normal subjects, EGF immunoreactivity was significantly increased in the epithelium of bronchitic subjects and submucosa of asthmatics, and, GM-CSF immunoreactivity was increased in both epithelial and submucosal cells of asthmatics and to a lesser extent in submucosa of bronchitics. A significant correlation was found between the number of epithelial or submucosal cells expressing TGF-beta in both asthma and chronic bronchitis and basement membrane thickness and fibroblast number. No such correlation was found for EGF or GM-CSF. in situ hybridization for TGF-beta 1 mRNA confirmed the results obtained by immunohistochemistry. By combining in situ hybridization and immunohistochemistry, it was found that eosinophils and fibroblasts were synthetizing TGF-beta in asthma and bronchitis. These data suggest that TGF-beta, but not EGF or GM-CSF, is involved in airways remodeling in asthma and chronic bronchitis.

Adolescent↗
PubMed1997

Effect of ageing on peak expiratory flow variability and nocturnal exacerbations in bronchial asthma.

The aim of this study was to evaluate the role of ageing on variability of airflow obstruction and on the specific pattern of nocturnal exacerbations ("morning dipping" of peak expiratory flow (PEF)) in asthma. Two groups of stable asthmatics (Group A: 23 patients, aged 14-47 yrs; Group B: 20 patients, aged 53-74 yrs), that were similar for duration of disease, degree of obstruction and response to bronchodilators, were studied. PEF was monitored four times daily for 2 weeks, and amplitude of variation and "morning dip" were calculated. Both PEF amplitude and "morning dip" were greater in the older patients (p<0.005). Amplitude was negatively correlated with baseline forced expiratory volume in one second (FEV1) in both groups (p<0.01); multiple correlation with age, duration of disease, baseline FEV1 and degree of reversibility was significant in the older group only. Morning dip was inversely correlated to baseline FEV1 (p<0.01) and reversibility (p<0.05). Nocturnal symptoms were reported by all of the five Group A "dippers", but by only 6 of the 13 Group B "dippers" (p<0.04). Ageing contributes to increased variability of airway calibre in asthma. Aged patients are potentially at risk because functional evidence of nocturnal asthma may frequently be accompanied by a poor subjective awareness. Therefore, a more extensive practice of PEF monitoring is recommended in aged asthmatics.

Adolescent↗
PubMed1997

Markers of acute airway inflammation.

In asthma, acute inflammation induced by allergen challenge in allergic patients leads to an early and a late phase reaction. Immunoglobulin E (IgE)-mediated cell activation plays a crucial role in acute inflammation and leads to the release of proinflammatory mediators, such as histamine, eicosanoids, platelet-activating factor, oxygen-free radicals, neuropeptides and cytokines. These mediators are capable of inducing constriction of airways smooth muscle, increased secretion of mucus, and vasodilatation, as well as several important biological events, including modulation of the expression of adhesion molecules in endothelial and epithelial cells, and of inflammatory cell recruitment. Clinically, acute airway inflammation is characterized by a bronchoconstrictive response with acute symptoms, including wheezing and dyspnoea which can be reversed by short-acting bronchodilators, among which beta 2-agonists play a major role.

Asthma↗
PubMed1997

Growth factors in asthma.

Asthma is a chronic inflammatory disease of the airways, with associated repair processes. Both inflammatory and repair processes appear to be strictly related, and can lead to several histopathological alterations of the bronchial mucosa, such as the shedding of epithelium and increased thickness of the basement membrane. The integrity as well as the alterations of the bronchial structure are the consequence of several biological events, such as cell proliferation and death, cell activation and inhibition, and extracellular matrix (ECM) production and degradation. These events are critically regulated by polypeptides called growth factors (GFs), which are able, functioning in an autocrine and paracrine fashion, to affect and modulate cell functions and ECM turnover. Although the importance of GFs has been widely demonstrated in other pulmonary conditions, such as lung fibrotic diseases, their possible involvement in the pathogenesis of inflammatory and postinflammatory processes in asthma is still not completely clear. The aim of the present review was to discuss the biological evidence concerning the role of several growth factors, such as transforming growth factor-beta (TGF-beta), epidermal growth factor (EGF), granulocyte/macrophage colony-stimulating factor (GM-CSF), platelet-derived growth factor (PDGF) and endothelin, in asthma and chronic bronchitis.

Asthma↗
PubMed1997

Different heart rate patterns in obstructive apneas during NREM sleep.

Both bradycardia and a trend to tachycardia have been reported in obstructive sleep apneas (OSA). Because heart rate (HR) behavior may yield information on parasympathetic activity during OSA, we analyzed HR in samples of consecutive apneic cycles in non-rapid eye movement (NREM) sleep, recorded in normotensive patients breathing room air (n = 7) and supplemental O2 (n = 4). In air, the patients showed different HR trends during apnea, as HR decreased (HR decreased), remained constant (HR=), or increased (HR increased). By multiple regression analysis, development of HR trends correlated with the HR fall in the late interapneic period, HR at first effort, the decrease in esophageal pressure, and the lengthening of inspiration during apnea (R2 = 0.42). O2 abolished HR decreased-OSA, whereas HR= and HR increased-OSA still occurred but at higher HR than in air. In both the air and O2 series, the HR fall preceding apnea correlated significantly with the degree of hypoxia reached in the previous apneic cycle. These data indicate a complex modulation of HR during OSA, with the HR fall in the late interapneic period possibly reflecting the effectiveness of parasympathetic cardiac control in OSA patients during sleep.

Adult↗
PubMed1996

Urinary leukotriene E4 in the assessment of nocturnal asthma.

BACKGROUND: Urinary leukotriene E4 (LTE4) is a marker of the body's production of cysteinyl LTs, important mediators of airway inflammation. The role of the latter in nocturnal asthma is a topic of increasing interest. OBJECTIVE: This investigation was aimed at determining whether nighttime attacks are associated with increased release of LTs, expressed by urinary LTE4, and the relationship between the two phenomena. METHODS: Three groups were studied: group A, seven control subjects; group B, nine asthmatic patients without nocturnal attacks; and group C, nine asthmatic patients with a comparable daytime FEV1 but who were experiencing nocturnal exacerbations (morning dips in peak expiratory flow greater than 20%). Urine was collected over 24 hours in three samples (9:00 AM to 3:00 PM; 3:00 PM to 9:00 PM; and 9:00 PM to 9:00 AM). LTE4 was measured by high-performance liquid chromatography and radioimmunoassay and expressed as nanograms per millimole of creatinine. RESULTS: No significant differences between urinary LTE4 were noticed within groups A and B. Conversely, in group C urinary LTE4 at night (geometric mean with 95% confidence interval; 35.16 with 28.77-42.85) was significantly higher than that of the other samples (respectively 23.12 with 17.78-30.06, p less than 0.05; and 25.18 with 21.03-30.13, p less than 0.02); it was also significantly higher than in all the samples of other groups. A significant (p less than 0.02) linear correlation was observed between morning dip in peak expiratory flow and the log urinary LTE4 in the nocturnal sample. CONCLUSION: These results indicate the role of LTs in nocturnal asthma and suggest that urinary LTE4 may be a useful marker of this condition.

Activity Cycles↗
PubMed1996

Release of transforming growth factor-beta (TGF-beta) and fibronectin by alveolar macrophages in airway diseases.

Asthma and chronic bronchitis are associated with airway remodelling, and airway macrophages are present in bronchial inflammation. TGF-beta and fibronectin released by alveolar macrophages possess a fibrogenic potency. The potential role of alveolar macrophages in airway remodelling was studied in asthma and chronic bronchitis by the release of TGF-beta and fibronectin. Alveolar macrophages were isolated by bronchoalveolar lavage in 14 control subjects, 14 asthmatics and 14 chronic bronchitics. The spontaneous and lipopolysaccharide (LPS)- or concanavalin A (Con A)-induced release of TGF-beta and fibronectin was measured by ELISA. Alveolar macrophages from chronic bronchitics spontaneously release greater amounts of TGF-beta and fibronectin than those from asthmatic and control subjects. Alveolar macrophages from asthmatics release greater amounts of TGF-beta and fibronectin than those from control subjects. The spontaneous release of TGF-beta is significantly correlated with that of fibronectin. Fibronectin release was significantly reduced after LPS stimulation, and TGF-beta release was significantly increased after LPS stimulation, except in chronic bronchitis patients. Con A increased the release of TGF-beta in cells from normal subjects. This study suggests that activated macrophages play a role in airway remodelling in chronic bronchitis and to a lesser extent in asthma.

Adult↗
PubMed1996

Cardiovascular and ventilatory response to isocapnic hypoxia at sea level and at 5,050 m.

To assess the effect of chronic hypoxic conditions on ventilatory, heart rate (HR), and blood pressure (BP) responses to acute progressive isocapnic hypoxia, we studied five healthy Caucasian subjects (3 men and 2 women). Each subject performed one rebreathing test at sea level (SL) and two tests at the Pyramid laboratory at Lobuche, Nepal, at the altitude of 5,050 m, 1 day after arrival (HA1) and after 24 days of sojourn (HA2). The effects of progressive isocapnic hypoxia were tested by using a standard rebreathing technique. BP, electrocardiogram, arterial oxygen saturation, airflow and end-tidal CO2 and O2 were recorded. For each subject, the relationships between arterial oxygen saturation and HR, systolic BP and minute ventilation (VE), respectively, were evaluated. At HA1, the majority of subjects showed a significant increase in VE and BP response and a decrease in HR response to progressive isocapnic hypoxia as compared to SL. At HA2, VE and BP responses further increased, whereas the HR response remained similar to that observed at HA1. A significant relationship between hypoxic ventilatory responses and both systolic and diastolic BP responses to progressive hypoxia was found. No significant correlation was found between hypoxic ventilatory and HR responses.

Adult↗
PubMed1996

ICAM-1 expression by lung cancer cell lines: effects of upregulation by cytokines on the interaction with LAK cells.

Intercellular adhesion molecule-1 (ICAM-1) expression by tumour cells may be involved in their interaction with defensive cells. In this study the surface ICAM-1 expression and soluble ICAM-1 (sICAM-1) production by five small cell lung cancer (SCLC) and five non-SCLC (NSCLC) cell lines was investigated. In addition, the effects of ICAM-1 upregulation by cytokines on the adhesion of lung cancer cells to allogeneic lymphokine-activated killer (LAK) cells and susceptibility to LAK cytotoxicity was also evaluated. ICAM-1 expression was assessed by flow cytometry. Soluble ICAM-1 release was measured by enzyme-linked immunosorbent assay (ELISA). Interaction with LAK cells was tested by adhesion and cytotoxicity assays. At baseline, SCLC lines did not express ICAM-1, while 4 of the 5 NSCLC lines expressed ICAM-1. ICAM-1 expression was induced by interferon-gamma (IFN-gamma) in 4 of the 5 SCLC lines and upregulated in 1 of the 5 NSCLC lines. ICAM-1 expression was induced by tumour necrosis factor-alpha (TNF-alpha) in 1 of the 5 SCLC lines (National Cancer Institute (NCI) H211), and upregulated in 2 of the 5 NSCLC lines (NCI H460 and NCI H838). Among the latter lines, one (NCI H838) released significant amounts of sICAM-1. Adhesion to LAK cells and susceptibility to LAK cytotoxicity were significantly higher in TNF-alpha-treated NCI H460 and NCI H211 cells, compared to untreated NCI H460 and NCI H211 cells. In contrast, no difference in adhesion to LAK cells and susceptibility to LAK cytotoxicity was detected between baseline and TNF-alpha-treated NCI H838 cells. Intercellular adhesion molecule-1 surface expression and soluble intercellular adhesion molecule-1 release may play an important role in interactions between lymphokine-activated killer cells and lung cancer cells.

Antineoplastic Agents↗
PubMed1995

Sequential chemoimmunotherapy for advanced non-small cell lung cancer using cisplatin, etoposide, thymosin-alpha 1 and interferon-alpha 2a.

A phase II study was performed to evaluate the clinical and immunological effects of a regimen of cisplatin (DDP) and etoposide (VP-16) combined with thymosin-alpha 1 (TA1) and low-dose interferon-alpha 2a (IFN) in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Chemoimmunotherapy cycles were repeated every 3 weeks. There were 24 responses (two complete, 22 partial) among 56 assessable patients. Median survival was 12.6 months. Overall, treatment was well tolerated. Natural killer cell activity and lymphocyte subtypes were depressed by chemotherapy, but this effect was less prominent in patients receiving TA1 and IFN in comparison with a concomitant group of patients treated with DDP and VP-16 only. The combination of DDP and VP-16 and TA1 and IFN is effective in advanced NSCLC with acceptable toxicity. However, the results of this study need to be confirmed in a randomised trial.

Adult↗
PubMed1995

Preoperative chemotherapy and immunochemotherapy for locally advanced stage IIIA and IIIB non small cell lung cancer. Preliminary results.

From January 1991 to November 1993, 110 patients with histologically confirmed stage IIIA and IIIB non-small cell lung cancer (NSCLC), were seen at our Institution. Our study was designed to evaluate whether redirection to surgery of otherwise unresectable patients may be obtained by preoperative therapy. Forty-nine patients were considered eligible for neoadjuvant treatment. Thirty-two (Group I) were treated with two or three cycles of cisplatin, vinblastine and mitomycin C and 17 (Group II) received two cycles of cisplatin, VP16, alpha 1 timosine and interferon. The overall response rate was 81.2% for Group I and 88.7% for Group II. Downstaging was predictive of resectability (P < 0.05). Forty-one patients (83.6%) underwent thoracotomy with 37 (75.5%) radical resections. Conservative techniques (bronchovascular reconstruction) (22 cases) were preferred over pneumonectomy (2 cases). The resectability rate was 84% for Group I and 87% for Group II (P = NS). Treatment-related complications were minor, with no deaths. Postoperative complications occurred in two cases in each group (7.4% and 14.3%). There was no histologic evidence of tumor in three patients. Two-year survival was 75% for Group I and 55% for Group II (P = NS). To date 35 patients who had complete resection are alive, and free of disease. We conclude that preoperative chemotherapy produces high response and resectability rates in both stage IIIA and IIIB unresectable NSCLC; radical resection using a conservative technique is possible in patients who are otherwise unresectable; no local recurrence occurred after radical resection; no significant differences were demonstrated between the two protocols.

Aged↗
PubMed1994

Theophylline suppresses the release of tumour necrosis factor-alpha by blood monocytes and alveolar macrophages.

The purpose of this study was to evaluate the effect of theophylline on tumour necrosis factor-alpha (TNF-alpha) release by human blood monocytes (BMo), and rat BMo and alveolar macrophages (AM). BMo and AM were incubated in the absence or presence of theophylline, and the cell-free supernatants were harvested and tested for TNF-alpha activity by bioassay. Theophylline dose-dependently reduced TNF-alpha release by human BMo: significant inhibition was observed at 100 microns (41 +/- 5.9% of controls) and at 50 microns (59 +/- 4.8% of controls), while the inhibitory activity of theophylline at 10 microns (71 +/- 8.9% of controls) was not statistically significant. This activity was maximal at 2 h and declined at 4 h (59 +/- 5.2% of controls) and 24 h (89 +/- 3.1% of controls). Northern analysis performed on ribonucleic acid (RNA) extracted from human BMo demonstrated that theophylline was able to reduce TNF-alpha gene expression. Comparable levels of inhibition of TNF-alpha release were observed on rat BMo and AM (rat BMo 42 +/- 4.9% of controls; rat AM 38 +/- 1.7% of controls), suggesting that BMo and AM are equally susceptible to suppression of TNF-alpha release induced by theophylline. These results indicate that theophylline suppresses TNF-alpha release by mononuclear phagocytes. Since TNF-alpha is involved in the pathogenesis of bronchial hyperresponsiveness and asthma, our results suggest that the therapeutic activity of theophylline might be partly related to its effect on TNF-alpha release.

Animals↗
PubMed1994

The cardiovascular effects of obstructive sleep apnoeas: analysis of pathogenic mechanisms.

Obstructive sleep apnoeas (OSA) exert immediate marked cardiovascular effects, and may favour the development of systemic and pulmonary hypertension in the long-term. As for the pathogenesis of the acute cardiovascular changes, the first studies high-lighted the role of OSA-induced hypoxia and mechanical changes. However, more recent work pointed to the role played by the arousal reaction terminating OSA, and to the activity of the autonomic nervous system during apnoea and inter-apnoeic phase. As for the pathogenesis of chronic cardiovascular changes, recent findings suggest that the link between OSA and systemic hypertension may be through an abnormal function of the carotid body and underline the importance of chronic intermittent hypoxia versus continuous hypoxia in the development of stable systemic hypertension. On the other hand, OSA do not appear to enhance strongly the development of stable pulmonary hypertension. In this review, we analyze OSA-induced cardiovascular changes with particular emphasis on to the interplay of the possible pathogenic mechanisms involved. Acute OSA-induced cardiovascular alterations during the apnoeic phase appear to result mainly from the mechanical effects of OSA, while during the interapnoeic phase they seem mostly determined by chemical factors (hypoxia, hypercapnia) and by the arousal reaction. In addition, the role of reflex changes elicited by resumption of ventilation should be reconsidered, since lung inflation seems to exert a positive effect on the cardiovascular changes occurring at the end of OSA. This would be in contrast with the inhibitory effects described as "lung inflation reflex", and deserves further study.

Blood Pressure↗
PubMed1994

Slow and fast changes in transmural pulmonary artery pressure in obstructive sleep apnoea.

Our purpose was to assess how pulmonary artery pressure changes in relation to hypoxia and oesophageal pressure during obstructive sleep apnoeas. Transmural systolic pulmonary artery pressure (Ppa,STM), oxyhaemoglobin saturation (SaO2) and oesophageal pressure were analysed in two samples of consecutive obstructive apnoeas in each of four patients. In the first samples (samples A; probably recorded during non-rapid eye movement (NREM) sleep), SaO2 swings were small and repetitive. In the second samples (samples B; probably recorded during rapid eye movement (REM) sleep), they were large and more variable. Oesophageal pressure oscillated similarly in the two groups of samples. In all cases, transmural systolic pulmonary artery pressure progressively increased throughout apnoeas, and subsequently decreased in the interapnoeic periods. However, both early and end-apnoeic transmural systolic pulmonary artery pressure, remained stable in samples A; whilst they progressively increased in samples B. Transmural systolic pulmonary artery pressure at the beginning of each apnoea was inversely correlated with SaO2 at the end of the preceding apnoea. These results suggest that transmural systolic pulmonary artery pressure is influenced by SaO2, but does not vary at the same speed as SaO2. In all cases, beat-by-beat analysis showed, as expected, that the lower the oesophageal pressure, the higher the transmural systolic pulmonary artery pressure however, at each oesophageal pressure level, transmural systolic pulmonary artery pressure was more variable and higher, in samples B. In conclusion, transmural systolic pulmonary artery pressure in obstructive apnoeas shows rapid changes, which reflect oesophageal pressure variations, and slower changes, which are likely to be caused by SaO2.

Blood Pressure↗
PubMed1994

Cytokine production and expression of adhesion molecules and integrins in tumor infiltrating lymphomononuclear cells of non-small cell carcinomas of the lung.

Localization of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and of their ligands, lymphocyte function-associated antigen-1 and very late activation antigen-4, was determined in non-small cell lung carcinomas and tumor-free lung. Messenger RNA expression for interleukins (IL) IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, tumor necrosis factor-alpha, transforming growth factor-beta, interferon-gamma, granulocyte-macrophages colony stimulating factor, and human perforin-1 was assessed by in situ hybridization on the same tissues. Intercellular adhesion molecule-1 was expressed in all blood vessels, whereas only a low number of vessels displayed vascular cell adhesion molecule-1 immunoreactivity. Tumor infiltrating lymphomononuclear cells consisted of lymphocyte function-associated antigen-1-positive cells and of a lower number of very late activation antigen-4-positive cells. All squamous cell carcinomas consisted of intercellular adhesion molecule-1-positive neoplastic cells infiltrated by lymphocyte function-associated antigen-1-positive tumor infiltrating lymphomononuclear and CD-la-positive Langerhans cells, whereas only a minor number of adenocarcinomas displayed a consistent number of intercellular adhesion molecule-1-positive neoplastic cells. Tumor infiltrating lymphomononuclear cells showed a wider production of cytokines when compared to bronchus-associated lymphoid tissue of tumor-free lung. Moreover, cells producing interferon-gamma, IL-4, and IL-5 were more numerous in squamous cell carcinomas than in adenocarcinomas. These findings indicate that the lung squamous cell carcinoma might represent a neoplastic microenvironment able to induce activation of tumor infiltrating lymphomononuclear cells more efficiently than the adenocarcinoma.

Aged↗
PubMed1993

Thyroarytenoid muscle activity in sleep apneas.

In normal subjects the thyroarytenoid muscle (TA), a vocal cord adductor, has phasic expiratory activity during wakefulness that disappears during non-rapid-eye-movement (NREM) sleep. Fiber-optic studies have reported absent or irregular vocal cord movements during obstructive apneas and vocal cord adduction during central apneas. This study was designed to investigate TA activity during NREM sleep in 14 subjects with sleep apnea by means of intramuscular wire electrodes. During central apneas, which were recorded in three subjects, continuous TA activity was observed. During obstructive apneas, which were recorded in all subjects, two different patterns of TA activity were observed: 1) absence of any activity until arousal and 2) phasic activity throughout the apnea. The first pattern was detected in six subjects, whereas both patterns were observed in the remaining eight subjects. No correlation was found between obstructive apnea characteristics and presence or absence of TA activity. In all subjects TA underwent a marked activation during arousal. While nasal continuous positive airway pressure was applied during NREM sleep TA activity was always absent. The persistence of TA activity during central apneas suggests that they may represent an extreme prolongation of neural expiratory discharge. We speculate that a variable interaction of different stimuli acting during obstructive apnea may activate TA, which, in turn, may contribute to glottic narrowing.

Adult↗