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Biomedical subjects

C Lisboa

Publications and source records attributed to C Lisboa.

At least 19 recordsLinked to original sources

Cd8(+)/V beta 5.1(+) large granular lymphocyte leukemia associated with autoimmune cytopenias, rheumatoid arthritis and vascular mammary skin lesions: successful response to 2-deoxycoformycin.

We report a case of CD8(+)/V beta 5.1(+) T-cell large granular lymphocyte leukemia (T-LGL leukemia) presenting with mild lymphocytosis, severe autoimmune neutropenia, thrombocytopenia, polyarthritis and recurrent infections with a chronic disease course. Immunophenotyping showed an expansion of CD3(+)/TCR alpha beta(+)/CD8(+bright)/CD11c(+)/CD57(-)/CD56(-) large granular lymphocytes with expression of the TCR-V beta 5.1 family. Southern blot analysis revealed a clonal rearrangement of the TCR beta-chain gene. Hematopoietic growth factors, high dose intravenous immunoglobulin and corticosteroids were of limited therapeutic benefit to correct the cytopenias. During the disease course, the patient developed a severe cutaneous leg ulcer and bilateral vascular mammary skin lesions. Treatment with 2-deoxycoformycin resulted in both clinical and hematological complete responses, including the resolution of vascular skin lesions. Combined immuno-staining with relevant T-cell associated and anti-TCR-V beta monoclonal antibodies proved to be a sensitive method to assess the therapeutic effect of 2-deoxycoformicin and to evaluate the residual disease.

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Bleomycin-induced chronic lung damage does not resemble human idiopathic pulmonary fibrosis.

Administration of bleomycin into the lungs of experimental animals has been utilized as a model to understand human pulmonary fibrosis. Most of the studies, however, have focused on early stages of the lung reaction. We hypothesized that chronic stages of the model may not mimic idiopathic pulmonary fibrosis, since in preliminary studies, lung volume and compliance were not decreased. Eight male Sprague-Dawley rats receiving intratracheal bleomycin (0.5 U/100 g body weight) underwent measurement of FRC, inspiratory capacity, and lung compliance 120 d later. Lung histologic changes were evaluated using light microscopy. Eight rats without intervention served as controls. Results show that our model, in early stages, has histologic changes no different from those previously described elsewhere. In chronic stages, however, the model does not behave as a restrictive syndrome: FRC is normal or increased, whereas lung compliance is normal. Focal peribronchiolar inflammation and fibrosis associated with paracicatricial emphysematous changes are the main histologic features of long-term lung remodeling after bleomycin. We conclude that while the chronic stages of the model may be informative in understanding mechanisms of fibrosis, care should be taken not to extrapolate to human idiopathic pulmonary fibrosis. We speculate that the model might resemble a particular subgroup of human interstitial lung disease, namely, those involving peribronchiolar structures.

Animals↗

Breathing pattern and gas exchange at peak exercise in COPD patients with and without tidal flow limitation at rest.

Expiratory flow limitation (FL) at rest is frequently present in chronic obstructive pulmonary disease (COPD) patients. It promotes dynamic hyperinflation with a consequent decrease in inspiratory capacity (IC). Since in COPD resting IC is strongly correlated with exercise tolerance, this study hypothesized that this is due to limitation of the maximal tidal volume (VT,max) during exercise by the reduced IC. The present study investigated the role of tidal FL at rest on: 1) the relationship of resting IC to VT,max; and 2) on gas exchange during peak exercise in COPD patients. Fifty-two stable COPD patients were studied at rest, using the negative expiratory pressure technique to assess the presence of FL, and during incremental symptom-limited cycling exercise to evaluate exercise performance. At rest, FL was present in 29 patients. In the 52 patients, a close relationship of VT,max to IC was found using non-normalized values (r=0.77; p < 0.0001), and stepwise regression analysis selected IC as the only significant predictor of VT,max. Subgroup analysis showed that this was also the case for patients both with and without FL (r=0.70 and 0.76, respectively). In addition, in FL patients there was an increase (p < 0.002) in arterial carbon dioxide partial pressure at peak exercise, mainly due to a relatively low VT,max and consequent increase in the physiological dead space (VD)/VT ratio. The arterial oxygen partial pressure also decreased at peak exercise in the FL patients (p < 0.05). In conclusion, in chronic obstructive pulmonary disease patients the maximal tidal volume, and hence maximal oxygen consumption, are closely related to the reduced inspiratory capacity. The flow limited patients also exhibit a significant increase in arterial carbon dioxide partial pressure and a decrease in arterial oxygen partial pressure during peak exercise.

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[Strength of inspiratory muscles in chronic heart failure and chronic pulmonary obstructive disease].

BACKGROUND: The maximal pressure generated by inspiratory muscles (PIMax) is an index of their strength which is diminished in both chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF). Although inspiratory muscle power output (IMPO), which includes both strength and velocity of shortening, has been shown to be reduced in COPD, there is no information regarding IMPO in CHF. AIM: To measure IMPO in patients with CHF and COPD. PATIENTS AND METHODS: We studied 9 CHF patients with functional capacity II and III and 9 patients with severe COPD. Eight normal subjects of similar ages were included as controls. Power output was measured using the incremental threshold loading test. RESULTS: Maximal IMPO was significantly reduced in both groups of patients. Power output developed with each increasing load was also diminished, basically as a consequence of a reduction in Vinsp. The degree of dyspnea at the end of the test was greater in COPD than in CHF patients and normal subjects. For a given level of power, dyspnea was also greater in patients than in normals subjects. There was no decrease in SpO2 during the test. CONCLUSIONS: IMPO is equally reduced in COPD and CHF patients. Power output is better related to dyspnea than PIMax, probably because of the inclusion of shortening velocity.

Analysis of Variance↗

[Selective training of respiratory muscles in patients with chronic heart failure].

BACKGROUND: Patients with chronic heart failure have a lower inspiratory muscle strength and fatigue endurance. AIM: To assess the effects of selective training of respiratory muscles in patients with heart failure. PATIENTS AND METHODS: Twenty patients with stable chronic heart failure, aged 58.3 +/- 3 years with an ejection fraction of 28 +/- 9%, were subjected to respiratory muscle training with threshold valves. The load was fixed in 30% of maximal inspiratory pressure (PImax) in 11 and in 10% of PImax in nine. Two sessions of 15 minutes, 6 days per week, during 6 weeks were done. Degree of dyspnea (Mahler score), maximal oxygen uptake, distance walked in 6 minutes, respiratory muscle function and left ventricular ejection fraction were measured before and after training. RESULTS: Both training loads were associated to an improvement in dyspnea (+2.7 +/- 1.8 and +2.8 +/- 1.8 score points with 30% PImax and 10% PImax respectively), maximal oxygen uptake (from 19 +/- 3 to 21.6 +/- 5 and from 16 +/- 5 to 18.6 +/- 7 ml/kg/min with 30% PImax and 10% PImax respectively, p < 0.05), PImax (from 78 +/- 22 to 99 +/- 22 and from 72 +/- 34 to 82.3 cm H20 with 30% PImax and 10% PImax respectively), sustained PImax (from 63 +/- 18 to 90 +/- 22 and from 58 +/- 3 to 69 +/- 3 cm H20 with 30% PImax and 10% PImax respectively), and maximal sustained load (from 120 +/- 67 to 195 +/- 47 and from 139 +/- 120 to 192 +/- 154 g with 30% PImax and 10% PImax respectively). The distance walked in 6 min only increased in subjects trained at 30% PImax (from 451 +/- 78 to 486 +/- 68 m). CONCLUSIONS: Selective training of respiratory muscles results in a functional improvement of patients with chronic heart failure.

Breathing Exercises↗

[Quality of life in patients with chronic obstructive pulmonary disease and the impact of physical training].

BACKGROUND: Health related quality of life (QoL) is severely impaired in COPD patients as a consequence of dyspnea and limited exercise tolerance, which lead to physical deconditioning and muscle atrophy resulting in weakness and fatigue. Psychosocial factors such as depression and anxiety also contribute to this impairment. AIM: To evaluate: a) the impact of COPD on quality of life, and b) the effect of 10 weeks of exercise training on exercise performance and on QoL. PATIENTS AND METHODS: The Spanish version of the Chronic Respiratory Questionnaire (CRQ) was applied to 55 COPD patients (FEV1 37 +/- 13% pred) for the assessment of QoL and in 30 of them submitted to exercise training for 10 weeks. Exercise performance was evaluated by measuring: six-minute walking distance, maximal workload (Wmax), maximal O2 consumption (VO2max) as well as endurance time, blood lactic acid, dyspnea and leg fatigue during a submaximal exercise. Trained patients were evaluated before and after training. RESULTS: COPD patients showed a reduction (mean +/- SD) in the four domains of the CRQ: dyspnea (3.1 +/- 0.9); fatigue (4.3 +/- 1.3); mastery (4.65 +/- 1.3), emotional function (4.1 +/- 0.97), and in Wmax and VO2max (52 +/- 16 Watt and 970 +/- 301 ml/min). No significant relationship between the impairment in exercise tolerance and in QoL was observed. Exercise training significantly improved the four domains of QoL (p < 0.0001), Wmax (p < 0.05), VO2max (p < 0.02) and endurance time (p < 0.001). Isotime exercise measurements of dyspnea, leg fatigue and lactic acid decreased after training (p < 0.001, each). No significant relation between changes in QoL and changes in exercise performance were observed. CONCLUSIONS: Our results demonstrate that QoL is seriously impaired in patients with COPD and confirm: (a) the lack of relationship of QoL to the usually measured physiological parameters, and (b) the beneficial effect of exercise training on QoL through the reduction of symptoms. These findings stresses the need of measuring quality of life in our patients if we want to evaluate the impact of therapeutic procedures on well-being from the patients' perspective.

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[The six minute walking test elicits lung hyperinflation in patients with severe chronic obstructive lung disease].

BACKGROUND: Exercise tolerance in patients with COPD is highly variable and poorly related to airways obstruction assessed by FEV1. These patients develop dynamic hyperinflation (DH) during an incremental exercise test which can be evaluated through a reduction in inspiratory capacity (IC). AIM: To evaluate: a) if the six minute walking test (6 MWD) induce DH reducing IC, b) if the reduction in IC is related to tidal expiratory flow limitation at rest (FL). SUBJECTS AND METHODS: Thirty eight stable COPD patients (28 FL and ten non FL during resting breathing, determined by the negative pressure technique). Inspiratory capacity was measured before and immediately after the 6 MWD test. Dyspnea, SpO2 and heart rate were measured before and after the test. RESULTS: Inspiratory capacity was lower in FL patients as compared to patients without FL (p < 0.005). Although no differences were found between groups in 6 MWD, dyspnea and HR, a significant reduction in IC after the walking test was observed only in FL patients (p < 0.0001). In addition, SpO2 fell significantly (p < 0.0001) after walking in the same group. CONCLUSIONS: Our results demonstrate that a moderate exercise such as the walking test induces DH and hypoxemia in patients with COPD and FL and stresses the importance of assessing DH by measuring IC in these patients.

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[Computer analysis of respiratory sounds in bronchial obstruction evaluation in small children that do not collaborate with spirometry tests].

BACKGROUND: There are changes in inspiratory breath sound intensity in patients with airway obstruction. Airway narrowing may change sound spectral characteristics. AIM: To define the characteristics of lung sounds at standardized air flow during methacholine challenge and to compare acoustic changes with transcutaneous oxygen tension (PtcO2) during induced airway narrowing. PATIENTS AND METHODS: Forty asthmatic children (20 male) aged 5.2 +/- 1 years and 40 normal children (18 male), aged 5.6 +/- 1 years were studied. All patients were free of respiratory tract infections one month before the study. A methacholine challenge from 0.06 to 8 mg/ml was performed; the test was ended when a fall in PtcO2 of > 20% from baseline was observed or if the final concentration was reached. Subjects breathed through a pneumotachograph aiming at flows of 0.4 to 0.6 l/s. Respiratory sounds were recorded using contact sensors at the suprasternal notch and at the posterior right lower lobe. From average spectra, power at low (100-200 Hz = P1) and high frequencies (400-2000 = P2) was calculated. Frequencies below which 50% (F50) and 99% (SEF90) of the spectral power between 100 and 2000 Hz was contained, were also calculated. RESULTS: In asthmatics, the metacholine concentration at which a 20% fall in PtcO2 was observed, was lower than in normal children (p < 0.05). There was an increase in P1 (p < 0.01) and a reduction in P2 (p < 0.01) during inspiration, in subjects that experienced a 20% reduction in PtcO2. Also, there was an increase in F50 and SEF99 during inspiration in lung sounds, but not over the trachea. CONCLUSIONS: Lung sounds analysis can be useful for the assessment of airway reactivity in asthmatic children.

Asthma↗

Role of inspiratory capacity on exercise tolerance in COPD patients with and without tidal expiratory flow limitation at rest.

Expiratory flow limitation promotes dynamic hyperinflation during exercise in chronic obstructive pulmonary disease (COPD) patients with a consequent reduction in inspiratory capacity (IC), limiting their exercise tolerance. Therefore, the exercise capacity of patients with tidal expiratory flow limitation (FL) at rest should depend on the magnitude of IC. The presented study was designed to evaluate the role of FL on the relationship between resting IC, other respiratory function variables and exercise performance in COPD patients. Fifty-two patients were included in the study. Negative expiratory pressure (NEP) uptake (VO2,max) were measured during an incremental symptom-limited cycle exercise. Twenty-nine patients were FL at rest. The IC was normal in all non-FL patients, while in most FL subjects it was decreased. Both WRmax and VO2,max were lower in FL patients (p<0.001, each). A close relationship of WRmax and O2,max to IC was found (r=0.73 and 0.75, respectively; p<0.0001, each). In the whole group, stepwise regression analysis selected IC and forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) (% predicted) as the only significant contributors to exercise tolerance. Subgroup analysis showed that IC was the sole predictor in FL patients, and FEV1/FVC in non-FL patients. Detection of flow limitation provides useful information on the factors that influence exercise capacity in chronic obstructive pulmonary disease patients. Accordingly, in patients with flow limitation, inspiratory capacity appears as the best predictor of exercise tolerance, reflecting the presence of dynamic hyperinflation.

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[Peroxide metabolism on respiratory muscles: effect of growth, maturation and aging].

BACKGROUND: Glutathione peroxidase (GSHPx) and catalase are two important cellular antioxidant enzymes involved in H2O2 and lipid-peroxide metabolism. AIM: To study the effects of growth, maturation and aging on the activity of these enzymes. MATERIAL AND METHODS: GSHPx and catalase specific activities were measured in samples of diaphragm and intercostal muscle of male Sprague-Dawley rats of different ages (21, 50, 70, 180 and 365 days), anesthetised with chloral hydrate (45 mg/100 g i.p.). RESULTS: The diaphragm and intercostal muscles did not differ in GSHPx activity at 21 days. After that, GSHPx activity increased progressively with age, but following a different pattern, in each muscle, suggesting an increase in enzyme substrates with age. In one year old animals, GSHPx activity was 5 times higher for the diaphragm and 3 times higher for the intercostal muscles, when compared with values observed at 21 days of age. Catalase activity also increased with age in the diaphragm but not in the intercostal muscles. CONCLUSIONS: GSHPx activity increases progressively with age in rat respiratory muscles, with a time course that is specific of each muscle. Catalase activity increases with age only in the diaphragm. These results support the hypothesis that antioxidants in respiratory muscles undergo specific regulatory changes with age.

Age Factors↗

[Effects of inspiratory muscle training on the oxygen cost of breathing in patients with chronic obstructive pulmonary disease].

BACKGROUND: Patients with chronic obstructive pulmonary disease have an increased inspiratory work, since they must overcome high loads due to increased airway resistance. AIM: To determine if the reduction in the metabolic cost of exercise observed in patients with chronic obstructive pulmonary disease (COPD) after inspiratory muscle training, was due to a reduction in the oxygen cost of breathing. PATIENTS AND METHODS: Nine patients with COPD (FEV1 39 +/- 13%) subjected to inspiratory muscle training, using a training load of 30% of maximal inspiratory pressure, during 10 weeks; 5 patients with COPD (FEV1 44 +/- 18%) not subjected to training, and 7 healthy controls (FEV1 110 +/- 10%) were studied. The cost of breathing was calculated as the difference in VO2 measured at rest and after breathing a gas mixture containing air and 5% CO2. Exercise VO2 was measured at submaximal exercise. RESULTS: Oxygen cost of breathing was increased in patients with COPD and it was inversely correlated with FEV1 (r = -0.86 p < 0.001). Inspiratory muscle training increased maximal inspiratory pressure and decreased exercise VO2. Oxygen cost of breathing increased in six and decreased in three trained patients. Changes in this parameter after training did not correlate with the reduction in exercise VO2 or the increment in maximal inspiratory pressure. CONCLUSIONS: The reduction in exercise VO2 after inspiratory muscle training is not due to a reduction in the oxygen cost of breathing.

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[Non-invasive mechanical ventilation in patients with severe stable COPD].

BACKGROUND: The benefits of non-invasive mechanical ventilation (NIMV) in hypercapnic patients with severe stable COPD remain controversial mainly due to their unknown mechanisms. AIM: To assess the clinical and physiological benefits of a 3 weeks period of intermittent NIMV and their underlying mechanisms in COPD patients. PATIENTS AND METHODS: Twelve patients (10 male) prospectively recruited (age 65 +/- 3 years, FEV1 27 +/- 2% predicted, PaO2 46 +/- 2 mmHg, PaCO2 55 +/- 2 mmHg) were submitted to NIMV using a commercially available system (BiPAP) 3 h a day, 5 days a week for 3 weeks. Arterial blood gases, 6 min walking distance, dyspnea (Mahler's scale), breathing pattern, PIMax, ventilatory drive (P0.1) and the impedance of the respiratory system (P0.1/V1/T1) were measured before and after NIMV. RESULTS: A significant improvement in PaO2, PaCO2, PIMax, dyspnea and exercise capacity was observed in addition to a trend for VT to increase and for respiratory rate (RR) to decrease. The impedance of the respiratory system showed a significant reduction. Ventilatory drive, normalized for PaCO2 levels, did not change. Improvement in PaCO2 was related to an increase in Vp whereas a significant association between the reduction in RR and the fall in respiratory system impedance was also found. CONCLUSIONS: Our study supports previous data demonstrating that NIMV improves clinical and physiologic parameters in advanced stable COPD and suggest that the underlying mechanism is a reduction in the inspiratory load. A randomized clinical trial is needed to confirm that this mechanism is operative.

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Effect of inspiratory muscle training with an intermediate load on inspiratory power output in COPD.

There is very little information about the effect of inspiratory muscle training on inspiratory flow (V'I) and thus on power output (PO) in patients with chronic obstructive pulmonary disease (COPD). In this study we aimed to evaluate the changes induced by training on the determinants of PO. Thirty one patients with severe COPD were randomly divided into: Group 1, trained with 30% maximal inspiratory pressure (PI,max); Group 2, with 10% PI,max; and Group 3 also trained with 30% PI,max, but the breathing pattern was evaluated while performing the training manoeuvres along inspiratory muscle training (IMT). All groups used a threshold device for 10 weeks. The PO for each of the loads during an incremental threshold test was evaluated prior to and after training. Maximal PO (POmax) increased in all groups, but the increment was higher in groups trained with 30% PI,max (p<0.005), mainly due to an increase in V'I. Group 3 showed a progressive increase in V'I (p<0.001) during the training manoeuvres in spite of an increase in load along IMT. In addition, the load after IMT was overcome with a shorter inspiratory time (tI) (p<0.02), a smaller tI/total duration of the respiratory cycle (t(tot)), (p<0.001) with no change in tidal volume or t(tot). The increment in POmax in this group correlated with the V'I generated while training (r=0.85; p<0.0001). We conclude that in patients with chronic obstructive pulmonary disease, the use of an intermediate threshold load for training improves power output mainly by increasing inspiratory flow, an effect consistent with an increase in shortening velocity of inspiratory muscles.

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[Experimental pulmonary emphysema in rats. Inflammatory phenomena and progression of lung damage].

BACKGROUND: Although the hamster model of elastase induced emphysema is well characterized, the rat model has received less attention. AIM: To evaluate the effect of a single intratracheal elastase dose on lung pathological changes of Sprague-Dawley rats. MATERIAL AND METHODS: Rats were injected with a single intratracheal elastase dose of 28 U/100 g body weight or saline and studied 7, 15, 30 and 365 days after injection. RESULTS: Forty percent of rats died in the first 48 hours after injection, six were sacrificed at 7 days, 6 at 15 days, 7 at 30 days and 12 at 365 days. Progressive centroacinar emphysema was found from day 7 after elastase, with a persistent inflammatory reaction in the vicinity of emphysematous areas. CONCLUSIONS: Present findings differ from the panacinar emphysema described in the hamster using a similar elastase dose.

Animals↗