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Biomedical subjects

V Grassi

Publications and source records attributed to V Grassi.

At least 19 recordsLinked to original sources

Aging and the respiratory system.

All the components of the respiratory system are affected by aging, though at different rates: i) the lung elastic recoil decreases; ii) PaO2 decreases and the D(A-a)O2 increases; iii) the chest wall becomes stiffer; iv) the inspiratory muscles loose strength; and v) the respiratory centres are less sensitive. Residual volume, closing volume and function residual capacity increase, whereas vital capacity and FEV1 progressively decrease. The flow volume curve becomes more convex to the volume axis at low lung volume. Whether these changes are due to aging or associated with aging is a matter of debate. However, the aging lung is more fragile in the face of respiratory and systemic diseases than the respiratory system of young adults. Nutrition, smoking habits and sleep-related disorders also affect the respiratory system. Although bronchial asthma may also appear in the elderly, chronic obstructive pulmonary disease is one of the most common respiratory diseases in advanced life and is a major cause of respiratory failure and ICU admission. Age in itself is not a risk factor of respiratory failure, but elderly patients have an increased risk of mortality for both acute respiratory failure (the failing lung), and exacerbated chronic ventilatory failure (the failing pump). Although advanced age can influence the final outcome of elderly patients from the intensive care unit (ICU), admission to the ICU as well as the institution of mechanical ventilation should not be denied on the basis of age alone, since the severity of illness, prior health status and admitting diagnosis have more weight than age in the final outcome.

Adult

Ineffectiveness of intravenous beta 2-agonists on improving exercise tolerance in patients with reversible chronic airway obstruction.

The effects on exercise tolerance after acute administration of beta 2-agonists were investigated in 11 patients with partly reversible chronic airway obstruction after 400 micrograms of salbutamol (S) given intravenously (i.v.) and after 400 micrograms i.v. of a new selective beta 2-agonist, broxaterol (B), by a cardiopulmonary incremental exercise test. At rest, while VE increased in respect to basal conditions (C) after S (from 13.3 +/- 2.2 to 14.4 +/- 2.8 l/min; p < 0.05) and after B (from 13.6 +/- 3.1 to 15.5 +/- 3.6 l/min; p < 0.05), VO2, VCO2 and VO2/HR showed no substantial variations. A small, not significant reduction of PaO2 was observed both after S (from 82.7 +/- 11.7 to 79.1 +/- 16.7 mm Hg) and B (from 81.6 +/- 10.5 to 78.0 +/- 11.0 mm Hg). The maximum workload increased neither after S (from 67.5 +/- 39.1 to 66.6 +/- 37.0 W) nor after B (from 65.7 +/- 39.3 to 60.0 +/- 35.8 W). At peak of exercise, VO2, VCO2 and VO2/HR did not change after S and B as compared with C, whereas VE remained higher after both beta 2-agonists throughout the effort. VO2 at ventilatory anaerobic threshold (AT) was significantly greater either after S (from 744 +/- 378 to 815 +/- 302 ml/min; p < 0.05) and after B (from 756 +/- 290 to 842 +/- 292 ml/min; p < 0.05). The PaO2 increase shown by these patients during effort was greater after beta 2-agonists administration, delta PaO2 from rest to peak of exercise amounting to 14.9 +/- 14.3 vs. 7.8 +/- 8.2 mm Hg after S and to 17.8 +/- 15.1 vs. 8.8 +/- 10.9 mm Hg after B, in respect to relative baseline (p < 0.05). We conclude that beta 2-agonists, when given acutely, do not improve exercise tolerance in patients with reversible chronic airflow obstruction, although these drugs can induce a small increment of ventilatory AT. In addition, arterial blood gases do not deteriorate at rest and are better preserved during exercise after beta 2-agonists.

Adrenergic beta-Agonists

Diurnal change of bronchial caliber and airway responsiveness in asthmatics during long-term treatment with long-acting beta 2-agonist salmeterol.

Measurements of bronchial caliber and airway sensitivity were performed 4 times during the day (at 9, 11, 16, and 22 hr) at basal conditions (baseline), following the first inhalation of 50 micrograms salmeterol (acute) and at the 21st, 90th and 150th day after the initiation of an uninterrupted long-term treatment with inhaled salmeterol (50 micrograms b.i.d., at 10 and 22 hr). In each period of the protective effect was assessed by computing the increase of the methacholine dose able to induce a 20% fall of the forced expiratory volume in the first second (PD20FEV1) in terms of doubling dose (DD), either against the respective 9-hour PD20FEV1 value (DD9hr) or against the corresponding baseline PD20FEV1 value (DDbaseline). After the first dose of salmeterol the forced expiratory volume in the first second (FEV1) increased significantly as compared with the 9-hour FEV1 and the corresponding baseline FEV1 at each observation time (p < 0.01). During regular treatment FEV1 was higher than baseline at the 21st and 90th day at each observation time (p < 0.05), whereas at the 150th day no significant FEV1 increments were observed at 9 hr and 22 hr. The acute protective effect exerted by salmeterol amounted to about 2 DD9hr (p < 0.05) and 2 DDbaseline (p < 0.05) at each observation time. At the 21st, 90th, and 150th day, however, no significant increase of DD9hr was found, although a mild decrease of airway sensitivity of 1 DDbaseline of magnitude was observed for all periods at each observation time. We conclude that in mild to moderate asthma salmeterol appears to rapidly lose its ability to improve bronchial responsiveness while it is effective in maintaining a well-sustained bronchodilation despite a small degree of tachyphylaxis.

Administration, Inhalation

Cardiopulmonary performance during exercise in acromegaly, and the effects of acute suppression of growth hormone hypersecretion with octreotide.

We studied 10 adult patients with active acromegaly (4 men and 6 women, mean age 55 +/- 5 years and mean body mass index 27.9 +/- 1.1 kg/m2). Control values for the echocardiographic and exercise studies were obtained from 10 normal subjects matched for sex and age (5 men and 5 women, age 51.1 +/- 3.7 years and body mass index 25.3 +/- 1 kg/m2). Each patient underwent: (1) blood sampling for growth hormone (GH) assay every 3 hours; (2) a 2-dimensional, guided M-mode echocardiographic study; and (3) a cycloergometric exercise test at baseline and after treatment with a portable pump infusing octreotide, 500 micrograms/24 hours subcutaneously. All patients had left ventricular hypertrophy. Systolic function indexes did not significantly differ among normal subjects, whereas baseline Doppler studies showed abnormalities in left ventricular diastolic filling in acromegalic patients. At anaerobic threshold and at maximal exercise, acromegalic subjects sustained a significantly (p < 0.05) decreased workload (54 +/- 23 vs 94 +/- 11 and 87 +/- 37 vs 152 +/- 15 W) compared with control subjects. After octreotide, baseline heart rate (79 +/- 7 vs 87 +/- 8 beats/min, p < 0.05) and serum GH levels significantly decreased compared with levels before administration of octreotide. Systolic and diastolic functional indexes at rest significantly improved after octrotide in acromegalic patients. Both at anaerobic threshold and at maximal exercise, workload and oxygen consumption were significantly increased after octretide administration. Exercise capacity at anaerobic threshold was not significantly different in acromegalic subjects after octreotide when compared with normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly

Effect of two beta 2-agonist drugs, salbutamol and broxaterol, on the growth hormone response to exercise in adult patients with asthmatic bronchitis.

The aim of our study was to evaluate the effect of the iv administration of two different beta 2- receptors agonists, salbutamol and broxaterol, on the growth hormone (GH) response to maximal exercise in 11 patients (8 males and 3 females; age range 18-65 yr; mean +/- SE age 56 +/- 13 yr; BMI 26.2 +/- 1.4 kg/m2) with chronic asthmatic bronchitis. All the subjects underwent four cycloergometric exercise tests (incremental workload until maximal predicted heart rate). At baseline, at maximal exercise, at the end of the recovery period and 60 min after the end of each exercise, blood samples were drawn for the assay of GH, glucose, insulin, lactates, norepinephrine and epinephrine. Two exercises were performed without treatment while the remaining two were performed 60 min after the administration of 400 micrograms of either salbutamol or broxaterol (both diluted in 10 ml of saline) according to a randomized double blind cross-over design. Both exercise tests performed without treatment caused a significant (p < 0.05) and similar GH peak with respect to baseline values (from 0.3 +/- 0.1 micrograms/L to 2.8 +/- 1.3 micrograms/L, mean of the two exercise tests). Salbutamol pretreatment blunted the GH response to exercise which caused a no more significant serum GH peak over the baseline levels (from 0.6 +/- 0.2 micrograms/L to 1.4 +/- 0.6 micrograms/L,). Moreover, broxaterol completely abolished the GH response to exercise (baseline level 0.6 +/- 0.2 micrograms/L; peak levels 0.4 +/- 0.1 micrograms/L). The serum GH peak after exercise + broxaterol was significantly (p < 0.05) lower as compared to exercise + salbutamol. In conclusion, we have demonstrated for the first time that beta 2 stimulation blunts the physiological GH response to maximal exercise in adult human subjects. It can be suggested that changes in brain neurotransmitters, possibly an increase in the alpha-adrenergic tone, are likely to be involved in this endocrine effects of exercise.

Adolescent

Cardiopulmonary adaptation to exercise after acute weight loss in severely obese subjects.

The aim of our study was to investigate the effects on baseline and exercise cardiopulmonary function and metabolic parameters of an acute (3-4 weeks) loss of at least 10% of initial weight in severely obese patients. Eight obese patients, 3 males and 5 females, mean age +/- SEM 42 +/- 6 yrs, body mass index (BMI) > 35 kg.m-2, underwent two cardiopulmonary function tests separated by 3 weeks of very low calorie protein-sparing diet (589 kcal.day-1) and a weight loss of 10% of initial weight (mean 8.43 +/- 0.72 kg). Eight normal subjects, matched for sex and age with the obese patients, served as controls. In the obese subjects, maximal workload (+15 +/- 3.6 W) and maximal oxygen consumption (V' O2) (+188 +/- 40.5 mL.min-1) were significantly increased after weight loss. Interestingly, exercise capacity at anaerobic threshold was not significantly different in obese subjects after weight loss with respect to normal subjects. Our results show that an acute but significant weight loss obtained with a very low calorie diet in obese patients is able to significantly improve maximal V' O2 and V' CO2 at anaerobic threshold. Moreover, this acute weight loss is able to partially reverse all of the cardiopulmonary alterations seen in obese patients both at baseline and during exercise.

Adaptation, Physiological

Nedocromil sodium versus theophylline in the treatment of reversible obstructive airway disease.

BACKGROUND: Previous clinical therapeutic research has shown that inhaled nedocromil sodium can replace maintenance oral sustained release theophylline in the management of asthma patients. OBJECTIVE: To compare directly the efficacy and safety of nedocromil sodium and sustained release theophylline. METHODS: Using a randomized, double-blind, double-dummy, parallel-group design, 105 patients with reversible obstructive airways disease (77 asthmatic patients) recruited from four referred-care clinics received, in addition to their existing therapy, 4 mg nedocromil sodium four times daily or sustained release theophylline (maximum daily dose 13 mg/kg) for 6 weeks. Patients with serum theophylline levels within the therapeutic range of 10 to 20 micrograms/mL were retained for efficacy analysis. All were included in a tolerability analysis. Day and nighttime symptoms, inhaled bronchodilator use, morning tightness, cough, and twice daily peak flows were recorded on diary cards. Disease severity, lung function and unusual events were evaluated bi-weekly, and opinion of treatment after 6 weeks. RESULTS: Both treatments improved symptoms, inhaled bronchodilator use and lung function to the same extent. Both treatments were very to moderately effective in > 70% patients. The occurrence of gastrointestinal (P < .05) and central nervous system (P < .01) unusual events was significantly lower for nedocromil sodium compared with theophylline treated patients. CONCLUSIONS: Nedocromil sodium and theophylline were equally effective in this group of patients but nedocromil sodium treatment was associated with significantly fewer side effects, and therefore may be the treatment of choice.

Adolescent

[Respiratory medicine in geriatrics. A cultural niche of relevant theoretical and practical importance].

Respiratory medicine in the elderly represents a topic of increasing interest in the developed countries, because of its peculiar clinical and therapeutical implications. In this respect, a deeper knowledge of the biology and physiology of aging lung is desirable: namely, the age-related immunological and structural changes involving the respiratory system do influence clinical presentation and response to the treatment in older people. A better understanding of the pharmacology in the elderly which is recognized to be different for several aspects from that of the general population, is mandatory in order to better approach these practical problems. This short review emphasizes the need of the "longitudinal", rather than "transversal", epidemiological surveys which are uniquely able to give useful information on the natural history, even in older populations. In addition, clinical and therapeutical peculiarities of some respiratory illnesses such as infectious lung diseases, including pulmonary tuberculosis, COLD and bronchial asthma, sleep-related respiratory disorders will be underlined. Finally, a few problems concerning the management of the geriatric subject with chronic respiratory disease will be analyzed, focusing mainly on the difficulties inherent in the inhalant therapy and functional evaluation of this kind of patients.

Aged

Uremic lung.

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Humans

Control of breathing and respiratory muscle strength in patients with multiple sclerosis.

In 11 patients with moderately severe multiple sclerosis, lasting 11.2 +/- 7.3 years, in stable condition, and in 10 age- and sex-matched control subjects, we investigated lung function, respiratory muscle strength, and ventilatory control system. Respiratory muscle strength was assessed by measuring maximal inspiratory and expiratory mouth pressures (Pimax and Pemax, respectively). Respiratory central drive was evaluated in terms of neuromuscular (P0.1) and ventilatory (Ve) output, breathing room air and during CO2 rebreathing. In the absence of any significant impairment of lung function, patients showed a reduction of Pimax and Pemax amounting to about 40 percent and 60 percent of the predicted value at functional residual capacity (FRC), respectively; a significant, inverse correlation was found between both Pimax and Pemax at FRC and the severity score of the disease. While at rest Ve was similar to that of control subjects, baseline P0.1 was significantly higher in patients (1.97 +/- 0.79 vs 0.97 +/- 0.20 cm H2O, p < 0.005). Compared with the control group, during CO2 rebreathing P0.1/PetCO2 slope, although less steep, was not dissimilar in patients (0.34 +/- 0.13 vs 0.46 +/- 0.19 cm H2O/mm Hg, NS); on the other hand, Ve/PetCO2 slope was much lower in the patient group (1.93 +/- 0.91 vs 3.27 +/- 1.11 L/min/mm Hg, p < 0.01) and was significantly related to the functional stage of disease and to Pimax and Pemax values at FRC. These results indicate that in patients with clinically stable, moderately severe multiple sclerosis, the respiratory muscle function is abnormal. Moreover, the inspiratory drive at rest is increased and the drive response to CO2 appears normal, while the ventilatory response to CO2 is significantly impaired. Respiratory muscle weakness (and/or lack of coordination) could explain, at least in part, the lower ventilatory response in these patients, whereas the mechanism of increased rate of the initial inspiratory force generation remains unclear.

Adult

Cardiorespiratory intermediate intensive unit: heart-lung interactions.

The heart and lung (the body's gas transport system) are neurally, mechanically, humorally and functionally linked. Several clinical-therapeutic consequences involve heart-lung interactions. Three of these conditions are described here: 1) pulsus paradoxus in asthma; 2) survival in chronic cor pulmonale; and 3) Cheyne-Stokes breathing in congestive heart failure. They provide examples of the pathophysiological and clinical complexity that such correlations involve. The most remarkable "effects" of the heart-lung relationship as a metabolic unit are represented by development of cardiorespiratory intensive care units, and efforts to bring about methods of monitoring cardiorespiratory function.

Asthma

Effects of beta 2-agonists during cardiopulmonary exercise test in COPD patients.

The aim of this study was to evaluate endocrine-metabolic, respiratory and cardiovascular effects of two beta 2-sympathomimetic selective agents, such as broxaterol and salbutamol, before and during cardiopulmonary exercise test (CPX). Twelve in-patients with chronic obstructive pulmonary disease (COPD) (with partially reversible airways obstruction) were included. Broxaterol (400 micrograms) and salbutamol (400 micrograms) were administered i.v., according to a double-blind, cross-over study. Before treatment and within 60 min after the administration of each agent, the patients underwent incremental CPX by bicycle ergometer to the maximum tolerable threshold. At these times the following variables were assessed: minute ventilation (VE), oxygen consumption (VO2), carbon dioxide production (VCO2), VE/VO2 ratio and O2 pulse, glycaemia, insulinaemia, plasma norepinephrine (NE) and epinephrine (E), arterial oxygen and carbon dioxide tension (PaO2 and PaCO2), plasma lactates, heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure. Spirometry was performed before and after the administration of each beta 2-adrenoceptor agonist. CPX brought about a significant increase in VE, VO2, VCO2, and O2 pulse. Broxaterol or salbutamol administration did not significantly modify the increases caused by CPX. At rest, 60 min after treatment, both bronchodilators caused a significant rise in glycaemia. A significant reduction of PaO2 (after broxaterol) and PaCO2 (after salbutamol) was observed at rest. In contrast, both agents caused no modification to potassium and insulin levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Evaluation of the efficacy of pidotimod in the exacerbations in patients affected with chronic bronchitis.

The efficacy and safety of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl)carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6), a new oral synthetic immunostimulating agent, were investigated in a multicentre study, performed in 10 university and hospital centres of pneumophthisiology and respiratory physiopathology, according to a double-blind vs. placebo experimental design. Primary objective of the investigation was to verify the efficacy of pidotimod against infectious exacerbations in patients affected with chronic bronchitis. 181 inpatients or outpatients (117 male, 64 female; mean age: 62.5 years), affected with chronic bronchitis, were enrolled in the study. Pidotimod 800 mg/die or placebo sachets were administered by oral route for 60 consecutive days, followed by a 60-day follow-up period. Clinical observations were performed at baseline (D 0), after 30 (D 30) and 60 (D 60) days of treatment, as well as at the end of the follow-up (D 120). Time and frequency of infectious relapses were considered as the target variable for the evaluation of the efficacy of the drug. Clinical picture, expectoration characteristics, spirometric parameters and laboratory tests were monitored to evaluate patients' conditions. The results indicate that pidotimod is significantly more effective than placebo against infectious relapses in patients suffering from chronic bronchitis. During the first month, 9% of patients treated with pidotimod were affected with an infectious relapse vs. 39.5% of patients treated with placebo (chi 2, p < 0.001). In the second month, infectious episodes were reported by 1.2% of patients treated with the drug vs. 46.1% of patients treated with placebo (chi 2, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Elevated cardiovascular mortality in subjects over 75 with low values of arterial pressure].

PURPOSE: The purpose of this study was to extend the observations from recent studies that have shown an increased mortality in elderly people with low blood pressure. METHODS: In 1982 we enrolled 88 subjects, 30 males, 58 females, aged 75-90 years, divided into 3 groups, according to their blood pressure and matched for sex, serum cholesterol, smoking and body mass index: Group I: 20 people with blood pressure equal or less than 120/75 mmHg; Group II: 46 subjects with blood pressure level ranging from 130/80 to 145/90 mmHg; Group III: 22 patients with hypertension (blood pressure equal or more than 160/95 mmHg). These three groups were followed for 6 years (1983-1988) to evaluate the mortality from cardiovascular diseases. During this period, no antihypertensive drugs were given, nor did any other treatment significantly modify the value of blood pressure. No patient changed starting group. RESULTS: Mortality from cardiovascular diseases was as follows: Group I: 14 deaths (mean age 82 +/- 5, 8 for heart failure, 2 for myocardial infarction, 4 for stroke); Group II: 8 (p < 0.001 versus Group I, mean age 81 +/- 3, 6 for heart failure, 1 for myocardial infarction, 1 for stroke); Group III: 4 (p < 0.001 versus Group I, mean age 80 +/- 2, 1 for heart failure, 1 for myocardial infarction, 1 for stroke and 1 for sudden death). CONCLUSIONS: This study adds further observations indicating an increase of mortality for cardiovascular diseases in subjects over 75 years with low levels of blood pressure, which could be more dangerous than moderately high levels in older people.

Aged

Respiratory prognosis in chest wall diseases.

In this short review focusing essentially on thoracic kyphoscoliosis, respiratory and cardiovascular abnormalities observed in different forms of this rib cage disorder are briefly described. Chest wall and pulmonary mechanics, respiratory muscles, gas exchange, pulmonary vasculature and regulation of ventilation can be markedly affected by kyphoscoliosis and a substantial growth of knowledge of these functional alterations has been allowed recently by new technological approaches. The pathophysiological process which leads to cor pulmonale and respiratory failure in some patients with kyphoscoliosis is analysed. The prognostic aspects of surgical and non-surgical management on pulmonary function are addressed.

Adult

[Changes in the heart rhythm and slow-release beta-2 agonist therapy (peroral) in asthmatic patients. A Holter study].

Slow-release formulations of salbutamol, used in asthmatic patients, may have few effects on cardiac rhythm. This study was designed to compare incidence and type of cardiac arrhythmias in a group of ten patients with stable bronchial asthma before and after 6 weeks treatment with a slow-release formulation of salbutamol. After a baseline spirometric and electrocardiographic evaluation, patients received placebo for a two-weeks period. At the end of this period patients repeated spirometry and carried out a 24-hour-ambulatory-E-Holter-monitoring. Subsequently, patients received for 6 weeks a treatment with a slow-release formulation of oral salbutamol. At the end of this period patients repeated spirometry, a 24-hour-ambulatory-EG-Holter-monitoring and potassium serum levels were controlled. We concluded from our study that, in patients with moderate bronchial asthma the treatment with an oral formulation of slow-release salbutamol may carry out a significant and durable bronchodilator effect, without causing important cardiac arrhythmias.

Administration, Oral