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Biomedical subjects

C Giuntini

Publications and source records attributed to C Giuntini.

At least 91 records · Page 5Linked to original sources

Phase II study of high-dose epirubicin in untreated patients with small-cell lung cancer.

Eighteen previously untreated patients with histologically confirmed small-cell lung cancer were treated with high-dose epirubicin (course 1, 100 mg/m2; courses 2-6, 140 mg/m2, day 1), every 3 weeks. Overall response rate was 33% (95% confidence limits, 14-52%), including two complete and four partial responses. The response rates for limited (n = 11) and extensive (n = 7) disease patients were 45% and 14%, respectively. With a median follow-up of 18 months, estimated 2-year survival of all patients was 29% and the median duration of response 18.5 months. The dose-limiting toxicity was myelosuppression, with a median granulocyte nadir of 1,150/mm3; 39% of patients had neutropenic fever. Nausea/vomiting, alopecia, and stomatitis were the most common nonhematological toxicities, usually mild to moderate. Acute cardiac toxicity was unusual and no episodes of congestive heart failure were observed. Cumulative doses of 800 mg/m2 were associated with moderate cardiotoxicity (grade 2), as assessed by endomyocardial biopsy and electron microscopy analysis. These results indicate that epirubicin, at the present doses and schedule, is an active single agent in patients with small-cell lung cancer, with acceptable general and moderate cardiac toxicity.

Aged↗

Pattern of airway response to allergen extract of Phleum pratensis in asthmatic patients during and outside the pollen season.

In order to evaluate the pattern of airway response to a specific bronchial provocative test (sBPT) with an extract of Phleum pratensis standardized in biological units (BU), we studied 27 patients with seasonal asthma due to grass pollen by means of allergologic evaluations, methacholine inhalation test and sBPT, outside the pollen season in all patients and, in 10 of them, also during the pollen season. We used a DeVilbiss 646 nebulizer with a dosimeter, giving increasing doses (0.01-2.5 BU) of the allergen solution and we monitored FEV1 to assess early (EAR) and late (LAR) airway responses. Outside the pollen season sBPT elicited an isolated EAR in 16 and a dual asthmatic response (DAR) in 11 patients. We observed no significant difference between EAR and DAR patients as regards the provocative dose causing a 15% fall in FEV1 (PD15FEV1) methacholine, EAR (expressed by PD15FEV1 allergen) or allergologic data. There was a significant relationship between PD15FEV1 allergen and PD15FEV1 methacholine (r = 0.43, p less than 0.05). The reproducibility of sBPT was assessed in 11 patients outside the pollen season. The correlation coefficients between the two tests were: r = 0.91, p less than 0.001 for the total delivered dose of allergen during sBPT; r = 0.79, p less than 0.01 for PD15FEV1 allergen; r = 0.95, p less than 0.001 for the maximum percent fall in FEV1 during LAR. Ten patients repeated all tests during the grass pollen season. PD15FEV1 methacholine and baseline FEV1 decreased significantly during the pollen season, but PD15FEV1 allergen did not change significantly during the season.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Improvement of screening for pulmonary embolism with a standardized questionnaire.

The anamnesis is believed to be poor in identifying patients with pulmonary embolism (PE), but the method of data collection may be critical for inference on this issue. We compared the prevalences of history findings recorded after a free verbal interview (VI) by the referring physicians with those recorded after completion of a standardized questionnaire (SQ) by the admitting physicians in a group of 177 consecutive patients referred to our Emergency Unit with the suspicion of PE (subsequently confirmed in 97). VI data were incomplete in 18 patients. In the remaining 159 patients, prevalences of symptoms and predisposing factors were higher after SQ than after VI. Accordingly, 8 items (obesity, prolonged immobilization, surgery, varicose leg veins, deep venous thrombosis, pleuritic chest pain, and sudden-onset dyspnea) were significantly more prevalent in patients with confirmed PE after SQ, compared to only 2 items (prolonged immobilization and pleuritic chest pain) after VI. When we tested for the agreement between the two methods of data collection, kappa values ranged from high values (for surgery and hemoptysis) to very low values (for prolonged immobilization and recurrent phlebitis). These results show that the use of an SQ could improve the accuracy of collecting clinical data in patients with suspected PE, as they are also consistent in separating patients with PE from those with unconfirmed suspicion of PE. Moreover, it allows the clinician to be alert towards findings which could be missed when not carefully searched for and which may be useful to raise or strengthen the suspicion of this disease.

Female↗

Carbon monoxide diffusing capacity, other indices of lung function, and respiratory symptoms in a general population sample.

To assess the relationships among single-breath diffusing capacity for CO (DLCOsb) (13), respiratory symptoms, and cigarette smoking in a general population sample, the data of 718 men and 894 women 20 yr of age or older were analyzed, and comparisons were performed with flow-volume curve (MEFV) variables and the slope of the alveolar plateau (DN2%/L) as well. Percent predicted DLCOsb and its correction for alveolar volume (DL/VA) were significantly lower in smokers than in nonsmokers. The relationship of presence/absence of respiratory symptoms and cigarette smoking with DLCOsb and DL/VA was significant. DLCO indices were almost always selected as discriminant variables in multivariate analysis between asymptomatic and symptomatic subjects. Poor concordance among lung function tests was evident: in men, 30% with abnormal (i.e., lower than 97.5% percentile) and 21% with normal DLCO indices also had abnormal MEFV parameters and/or DN2%/L. In women, the corresponding figures were 24 and 10%, respectively. In men, when considering only DLCO indices, the percentage of symptomatic subjects with abnormal lung function tests ranged from 33% in those with at least one symptom to 45% in those complaining of dyspnea. When the proportion of symptomatic subjects with DN2%/L and MEFV abnormalities were added, it increased to 56 and 66%, respectively. However, in women the proportion of symptomatic subjects with abnormal lung function indices was very small. These results indicate the usefulness of including CO diffusing capacity in epidemiologic surveys in the detection of abnormalities.

Adolescent↗

Natural course of treated pulmonary embolism. Evaluation by perfusion lung scintigraphy, gas exchange, and chest roentgenogram.

Perfusion lung scintigrams, pulmonary gas exchange data, and chest roentgenograms were obtained in 33 patients during acute embolism and over the following six months in order to assess their clinical usefulness in monitoring the effect of therapy. To this purpose, the measurement of pulmonary gas exchange and the presence of chest x-ray findings were compared with perfusion lung scintigraphic abnormalities both at diagnosis and after 7, 30, and 180 days during treatment. More than 50 percent of the pulmonary arterial tree was obstructed at diagnosis, and a large part of perfusion recovery was complete within the first month. All of the gas exchange parameters were abnormal at diagnosis, and the rate of their improvement was related to that of perfusion recovery. Interestingly, PaO2st (ie, PaO2 corrected for hyperventilation) and VE tended to return to normal during the first month as a consequence of the progressive recovery of perfusion, whereas oxygen and carbon dioxide gradients and physiologic dead space showed the persistence of some abnormalities six months after diagnosis. Significant correlations were observed between the number of ULSs evaluated on the perfusion lung scintigram (and considered an index of the severity of pulmonary embolization) and all of the gas exchange parameters at diagnosis (correlation coefficients averaged from 0.41 to 0.73) and after 7 and 30 days. The enlargement of the right descending pulmonary artery and particularly the "sausage" sign and the Westermark sign were significantly associated with a higher degree of gas exchange impairment and with a more severe embolization. In conclusion, this study demonstrates that perfusion lung scintigraphy has a primary role in monitoring the recovery of patients with pulmonary embolism under treatment. Moreover, the chest roentgenogram may help in this purpose. A second major result is that the simple measurement of some gas exchange parameters may allow the assessment of functional recovery of these patients, thus giving additional information about the effect of therapy.

Carbon Dioxide↗

Bronchoalveolar lavage and morphology of the airways after cessation of exposure in asthmatic subjects sensitized to toluene diisocyanate.

To evaluate the morphologic basis of the different outcomes of toluene diisocyanate (TDI) asthma after quitting occupational exposure, we examined ten patients with TDI asthma who showed, at diagnosis, a positive TDI challenge test and nonspecific bronchial hyperresponsiveness (NSBH) to methacholine. After diagnosis, all patients ceased work and a 4- to 40-month follow-up was obtained with three to eight determinations of the cumulative dose producing a 15 percent fall in FEV1 (PD15FEV1) methacholine in each patient. Bronchoalveolar lavage (BAL) and biopsy of bronchial muscosa were performed 3 to 39 months after cessation of work, in the absence of acute exacerbations of the disease. Total cell count in BAL fluid was moderately increased in four of ten patients, eosinophils were increased in five of ten patients, and neutrophils were increased in eight of ten patients. Mucosal biopsy specimens of main or lobar bronchi were available in eight of ten patients; epithelial damage and thickening of basement membrane was observed in almost all patients, as well as a mild-to-moderate inflammatory reaction in the submucosa, mainly represented by lymphocytes, eosinophils, and neutrophils. No relationship was observed between the cellularity of BAL and the degree of NSBH at the time of BAL; mean values of total cells and differential count were not different between patients with presence or absence of the different histologic findings. Mucosal biopsy and BAL were performed also in four subjects exposed to dusts without respiratory symptoms or NSBH; similar findings were obtained except for the absence of eosinophils in BAL and a lesser degree of basement membrane thickening and inflammatory reaction in the submucosa. The study of the changes in NSBH after quitting exposure showed that five of ten patients had a significant improvement in NSBH to methacholine, as evaluated by a positive significant linear regression between months of work cessation and PD15FEV1 methacholine; only one of these five patients had an increased number of eosinophils in BAL fluid. By contrast, four of the five patients with persistent NSBH after quitting exposure had an increased number of eosinophils in BAL. We suggest that persistent NSBH in TDI asthma after cessation of work may be related to an inflammatory reaction in which eosinophil infiltration seems to be a major determinant.

Adult↗

Pulmonary lipid peroxidation in cigarette smokers and lung cancer patients.

Lipid peroxidation (LPO) was studied in lung tissues of patients with lung cancer (LC, n = 37) or nonlung cancer (NLC, n = 13) and its relationships with the smoking habits and the degree of airway obstruction were investigated. Specimens of peripheral lung parenchyma, free of tumor tissue, were taken and the malondialdehyde (MDA) content was measured in the S-12 fractions. Airway obstruction was assessed by flow-volume curves, and data were expressed as percentage of the predicted values. Cigarettes smoked were expressed as pack-years. The patients with LC and NLC did not differ by MDA content, age, and number of pack-years. On the contrary, FEF75-85 and MEF75 were significantly lower in LC than in NLC patients (p less than 0.05). The MDA content was inversely correlated to number of days patients had refrained from smoking (r = -0.66, p less than 0.001). The MDA content was higher in recent smokers (ie, people smoking during the last 30 days before surgery) than in the other patients (0.136 +/- 0.007 vs 0.116 +/- 0.007 mumol/g of tissue, p less than 0.05) and, by considering only recent smokers, MDA content was higher in LC patients (0.144 +/- 0.008 mumol/g of tissue) than in NLC patients (0.113 +/- 0.014 mmol/g tissue, p = 0.059). When patients were divided into "high MDA" and "low MDA" groups, MEF75 was much lower in the high MDA group (35.1 +/- 3.4 percent) than in the low MDA group (55.1 +/- 8.1 percent) (p less than 0.01). These results suggest the following: (1) enhanced level of prooxidant state in the lungs is associated with recent cigarette smoking; (2) LC patients may be more prone than respective NLC patients to oxidative stress; (3) MDA level and degree of small airway obstruction were associated and differed between LC and NLC patients even though these groups did not differ in the percentage of recent smokers; and (4) a common free-radical mediated pathway may be active for both LC and small airway obstruction.

Glutathione↗

Carcinogen metabolism studies in human bronchial and lung parenchymal tissues.

The pulmonary metabolism of xenobiotics was investigated by measuring the glutathione content and the activity of the aryl hydrocarbon hydroxylase, epoxide hydrolase, glutathione S-transferase, and uridine 5' -diphosphoglucuronosyl transferase enzymes in S-12 fractions of bronchial tree and peripheral lung parenchyma obtained at surgery from 21 patients. In parallel, the same preparations were used to assess either the activation of promutagens, i.e., benzo(a)pyrene, 2-aminofluorene, cyclophosphamide, and a cigarette smoke condensate, to metabolites reverting his- Salmonella typhymurium strains, or the decrease of direct-acting mutagens, i.e., sodium dichromate, 4-nitroquinoline N-oxide, epichlorohydrin, and ICR 191. As compared to bronchus preparations, parenchymal preparations contained considerably higher concentrations of reduced glutathione, had a significantly higher epoxide hydrolase activity, and, as assessed by means of a quantitative index, were more efficient in activating 2-aminofluorene and in reducing the mutagenicity of dichromate and 4-nitroquinoline N-oxide. These data may suggest that parenchymal lung tissue is more capable than bronchial tissue to detoxify reactive intermediates of xenobiotics, possibly explaining the greater susceptibility of bronchi to cigarette smoke-induced cancers.

4-Nitroquinoline-1-oxide↗

Prospective study of a standardized questionnaire to improve clinical estimate of pulmonary embolism.

A standardized questionnaire was administered to 100 patients suspected of having pulmonary embolism to investigate whether clinical data may be reliably used in the decision-making process of such patients. Questionnaire data were compared with lung scintigraphy outcome and 16 variables were selected as significantly associated with the scintigraphic diagnosis. Based on these variables, patients with abnormal scintigraphy compatible with pulmonary embolism and patients with scintigraphy not compatible with embolism were classified in accordance with the scintigraphic diagnosis. When these 16 variables were tested in an additional validation group, clinical and scintigraphic diagnosis matched in most cases. These results show that clinical data can be used to predict the outcome of lung perfusion scintigraphy in patients suspected of pulmonary embolism. Use of a standardized questionnaire can improve the accuracy of pretest assessment of such patients and positively influence the decisions to start heparin coverage or obtain pulmonary angiography.

Electrocardiography↗

Estimates of mean alveolar gas in patients with chronic airways obstruction.

Alveolar to arterial differences (AaD) may be computed from representative alveolar gas pressures (PA). These are particularly difficult to obtain in patients with chronic airways obstruction (CAO) and severe inhomogeneity of the ventilation/perfusion (VA/Q) ratio. In 25 such patients, using a computerized mass spectrometer, representative values of alveolar gas were obtained: 1. as end-tidal concentrations (ET); 2. using the alveolar air equation with PACO2 derived from Bohr's equation (BE); 3. putting PACO2 = PACO2 into the alveolar air equation to compute ideal O2 alveolar pressure (ID); 4. applying Rahn's definition of "mean" alveolar gas (RD), i.e. taking within each jth breath, the alveolar pressures corresponding to the moment when the instantaneous gas exchange ratio R(t)j equals the overall exchange ratio for that breath Rj. During quiet breathing, the point where R(t)j equals Rj occurred at 71% of tidal volume (VT). Alveolar pressures by BE and RD resulted in similar values (115.5 +/- 6.9 and 115.5 +/- 6.6 mmHg for O2 and 30.3 +/- 5.7 and 30.8 +/- 5.7 mmHg for CO2, respectively), but they were significantly different from those by ET and ID (106.2 +/- 9.5 and 95.6 +/- 13.5 mmHg for O2 and 36.3 +/- 7.7 and 48.2 +/- 11.2 mmHg for CO2, respectively). These findings may be explained considering that PA(BE) and PA(RD) represent both high and low VA/Q units, whereas PA(ET) and PA(ID) represent mainly low VA/Q units. AaDCO2 by RD and BE appeared proportional to the severity of CAO as estimated from VT. Automated techniques make it possible to substitute end-tidal determinations with more accurate estimates either by measuring anatomical dead-space and using Bohr's equation or by applying Rahn's definition.

Aged↗

Vagal reflexes and asthma.

Although vagal reflexes are well documented in animal models of airway hyperresponsiveness, their importance in asthmatic attacks in man is less documented. Indeed most of the stimuli that can trigger bronchoconstriction act only partially through a cholinergic reflex. However, inflammatory mediators released in airways during asthma attacks may stimulate different sites of cholinergic pathways, i.e. in the sensory receptors, afferent, efferent, ganglionic or postganglionic sites. Further studies are required to assess the real influence of chemical mediators on vagal activity in asthmatic subjects during spontaneous or induced bronchoconstriction.

Animals↗

Effects of childhood and adolescence-adulthood respiratory infections in a general population.

The role of childhood respiratory infections before 12 yrs of age (CRI) and during adolescence-adulthood (ARI) was studied in a general population sample (n = 3,289), living in an unpolluted area of Northern Italy. The presence of respiratory symptoms and diseases, as well as risk factors for obstructive airways disease (OAD), was assessed by a standardized questionnaire. Forced vital capacity and derived expiratory flows, and single-breath diffusing capacity were measured using computerized instrumentation. There were 1,185 (36.2%) subjects who reported pertussis (PT), 374 (11.4%) recurrent chest colds, pneumonia and croup, singly or in combination, with or without pertussis (CRI), and 1,718 (52.4%) reported no respiratory infections in childhood (NOCRI). Prevalence rates of respiratory symptoms and diseases were significantly higher in subjects of the CRI group in all ages, and in older smokers. Wheeze and attacks of shortness of breath with wheeze were significantly higher in younger nonsmoking subjects with a history of CRI. Respiratory symptoms and diseases were not more prevalent in subjects of the PT group. Prevalence rates of respiratory symptoms and diseases were significantly higher in subjects with a history of ARI, both in smokers and nonsmokers. Lung function parameters adjusted for sex, age and smoking were significantly lower in CRI subjects; PT subjects showed lower values than NOCRI subjects. A significantly higher prevalence rate of ARI was present in subjects who reported CRI, both in smokers and nonsmokers. Subjects with both CRI and ARI showed the highest prevalence of respiratory symptoms and diseases. In addition, they had the lowest lung function values regardless of smoking habit.

Adolescent↗

Prevalence of asthma and asthma symptoms in a general population sample of north Italy.

The prevalence rates of asthma and asthma symptoms were investigated in a general population sample (n = 3,289) living in a rural area of northern Italy. The subjects received a standard questionnaire and performed lung function tests with automated equipment. The overall prevalence rate of reported diagnosis of asthma was 5%. In young nonsmokers of both sexes the prevalence rates of reported diagnoses were higher than those of symptoms whilst the reverse occurred in older age groups. The prevalence rates decreased from childhood to young adults and increased again in older age groups. In smokers, reported diagnoses and symptoms increased with age and the prevalence rates of symptoms were always higher than those of diagnoses. Smokers with symptoms and reported diagnoses had lower lung function parameters than those with only symptoms. The distribution of asthma symptoms in our population indicates the importance of cigarette smoke and other environmental factors in the expression of the disease.

Adolescent↗

Presence of epoxide hydrolase and glutathione S-transferase in human pulmonary alveolar macrophages.

Pulmonary alveolar macrophages (PAMs) were obtained from 11 patients by bronchoalveolar lavage. Epoxide hydrolase and glutathione S-transferase in sonicated PAMs were measured using benzo(a)pyrene-4,5-oxide as the substrate. The activity of epoxide hydrolase was 0.24 +/- 0.10 nmol/min/mg protein (mean +/- SD), and of glutathione S-transferase 0.22 +/- 0.12 nmol/min/mg protein. There was a significant difference in enzyme activities in the PAMs from smokers and non-smokers. Epoxides may be metabolized in PAMs.

Epoxide Hydrolases↗

A computer-based method for on-line acquisition and analysis of bronchial challenge test.

We developed a computer program for the optimization and management of data collection in order to compute the change of forced expiratory volume in the first second (delta FEV1), provocative doses and to plot the dose-response curve for bronchial challenge test. Doses of methacholine are entered via the keyboard and forced vital capacity (FVC) with the highest FEV1 value obtained in each step is selected. When the imposed threshold of response has been reached, doses of administered methacholine and corresponding spirometric parameters are displayed and printed. Dose-response relationships are analysed: the increase of delta FEV1 for each unit of metacholine is computed in the interval between the two doses where delta FEV1 reached one of the imposed values (i.e. 15% or 20% or 30%). Finally spirometric values, dose-response curve and provocative doses are shown in a print-out. Computer values of provocative doses are higher than those obtained manually. This difference may be ascribed to the incorrect manual linear extrapolation. In conclusion the computer program is able to reduce consistently the time spent to analyze data from bronchial challenge test and allows a more precise determination of provocative doses by avoiding also inter-intra individual errors.

Asthma↗

Ventilation-perfusion heterogeneity and gas exchange variables in acute pulmonary embolism evaluated by two different computerized techniques.

The mechanisms by which the disturbances of gas exchange develop in human pulmonary embolism are unknown. We investigated whether the inequality of ventilation-perfusion ratio is associated with the abnormalities of pulmonary gas exchange as evaluated by two different computerized techniques. We measured the alveolar to arterial gradients of oxygen and carbon dioxide by means of a computer based system with a mass spectrometer and the ventilation-perfusion distributions by the multiple inert gas technique in 5 patients with acute pulmonary embolism. In these subjects there was a marked ventilation-perfusion inhomogeneity, as detected from inert gases and this finding was in agreement with the impairment of the alveolar to arterial gradients and of their derived indexes. Consideration on the responsible mechanisms for the disturbances of gas exchange are also reported. In conclusion these two computerized techniques provide a useful assessment of the ventilation-perfusion relationships in order to explain the disturbances of gas exchange in critically ill patients.

Acute Disease↗