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Biomedical subjects

Simonetta Monti

Publications and source records attributed to Simonetta Monti.

16 recordsLinked to original sources
PubMed2006

No evidence of chromosome damage in chronic obstructive pulmonary disease (COPD).

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in industrialized countries. It is characterized by a progressive airflow limitation resulting from an abnormal inflammatory response of the lungs to inhaled gases and particles. Since oxidative stress is thought to play a role in COPD, and since increased oxidative stress is associated with chromosomal instability in several diseases, we investigated whether such relationship also exists in COPD. Whole blood lymphocytes from 49 COPD patients and 48 age- and sex-matched controls were cultivated in vitro and cytogenetic damage was evaluated by micronucleus (MN) and sister-chromatid-exchange (SCE) assays. In patients with COPD, MN frequency was not significantly different from that of controls. Similarly, SCE frequency did not differ in the two groups suggesting no disturbance in DNA replication. Unlike other diseases characterized by oxidative stress, COPD does not appear to be associated with DNA damage.

Aged↗
PubMed2006

Computer-aided diagnosis of emphysema in COPD patients: neural-network-based analysis of lung shape in digital chest radiographs.

Several abnormalities of the shape of lung fields (depression and flattening of the diaphragmatic contours, increased retrosternal space) are indicative of emphysema and can be accurately imaged by digital chest radiography. In this work, we aimed at developing computational descriptors of the shape of the lung silhouette able to capture the alterations associated with emphysema. We analyzed two-sided digital chest radiographs from a sample of 160 patients with chronic obstructive pulmonary disease (COPD), 60 of which were affected by emphysema, and from 160 subjects with normal lung function. Two different description schemes were considered: a first one based on lung-silhouette curvature features, and a second one based on a minimal-polyline approximation of the lung shape. Both descriptors were employed to recognize alterations of the lung shape using classifiers based on multilayer neural networks of the feed-forward type. Results indicate that pulmonary emphysema can be reliably diagnosed or excluded by using digital chest radiographs and a proper computational aid. Two-sided chest radiographs provide more accurate discrimination than single-view analysis. The minimal-polyline approximation provided significantly better results than those obtained from curvature-based features. Emphysema was detected, in the entire dataset, with an accuracy of about 90% (sensitivity 88%, specificity 90%) by using the minimal-polyline approximation.

Humans↗
PubMed2006

Cryptic haplotypes of SERPINA1 confer susceptibility to chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity worldwide. While cigarette smoking is a major cause of COPD, only 15% of smokers develop the disease, indicating major genetic influences. The most widely recognized candidate gene in COPD is SERPINA1, although it has been suggested that SERPINA3 may also play a role. To detect cryptic genetic variants that might contribute to disease, we identified 15 SNP haplotype tags from high-density SNP maps of the two genes and evaluated these SNPs in the largest case-control genetic study of COPD conducted so far. For SERPINA1, six newly identified haplotypes with a common backbone of five SNPs were found to increase the risk of disease by six- to 50-fold, the highest risk of COPD reported to date. In contrast, no haplotype associations for SERPINA3 were identified.

Aged↗
PubMed2006

Survival and restoration of pulmonary perfusion in a long-term follow-up of patients after acute pulmonary embolism.

We followed prospectively 834 consecutive patients (70% inpatients), evaluated for suspected pulmonary embolism, for a median time of 2.1 years (range, 0-4.8 yr), and compared the survival rates in patients with proven pulmonary embolism (n=320) with those without (n=514). In multivariate analysis, we modeled the probability of surviving in patients with pulmonary embolism as a function of the extent of pulmonary vascular obstruction at baseline. Among patients with pulmonary embolism, a scintigraphic follow-up was pursued to assess the restoration of pulmonary perfusion over a 1-year period. We found that massive pulmonary embolism (vascular obstruction>or=50%) is a risk factor for mortality within the first few days after onset but, subsequently, has no significant effect on survival. The adjusted risk of death in patients with massive pulmonary embolism was 8-fold higher than in patients without embolism within the first day after the incident event. By contrast, the adjusted risk of death for patients with minor or moderate pulmonary embolism (vascular obstruction<50%) was no higher than in patients without embolism at any time after onset. Most of the patients who survived a year after pulmonary embolism showed a nearly complete restoration of pulmonary perfusion with a considerable improvement in arterial oxygenation. Four (1%) of the 320 patients with pulmonary embolism at presentation developed chronic thromboembolic pulmonary hypertension. These patients featured persistent large perfusion defects in sequential lung scans. Pulmonary embolism with vascular obstruction>or=50% is a strong, independent predictor of reduced short-term survival. This underscores the need for a prompt diagnosis of the disease. Monitoring the resolution of pulmonary embolism by lung scanning may prove useful in identifying patients with persistent perfusion abnormalities who may be at risk of chronic thromboembolic pulmonary hypertension.

Adolescent↗
PubMed2005

Comparison of 3 clinical models for predicting the probability of pulmonary embolism.

Two clinical models have been described to predict the probability of pulmonary embolism: the Canadian (or Wells) model, and the Geneva model. A third model has been developed recently at our institution (the Pisa model). We compared the performance of the 3 models in 215 consecutive patients with suspected pulmonary embolism. The clinical probability predicted by the models was categorized as low, intermediate, or high. In all patients, pulmonary angiography was used as the reference diagnostic standard. In patients with pulmonary embolism, the extent of pulmonary embolization was assessed on the lung scan as an index of disease severity. The prevalence of pulmonary embolism was 43.3%, and the median extent of pulmonary embolization at diagnosis was 39.8% (range, 4.5%-75.3%). The proportions of patients categorized as having low, intermediate, or high probability were, respectively: 12%, 60%, and 28%, for the Geneva model; 30%, 55%, and 15%, for the Wells model; 37%, 37%, and 26% for the Pisa model. The frequencies of pulmonary embolism in the low, intermediate, and high probability categories were, respectively: 50%, 39%, and 49% for the Geneva model; 12%, 54%, and 64% for the Wells model; 5%, 42%, and 98% for the Pisa model. Among patients with pulmonary embolism, there was a strong, positive relation between clinical probability predicted by the Pisa model and the extent of pulmonary embolization. The Pisa model proved more accurate than the 2 other models. It may be useful to physicians in defining precisely the pretest probability of pulmonary embolism.

Adolescent↗
PubMed2004

Usefulness of ultrasound lung comets as a nonradiologic sign of extravascular lung water.

The "comet-tail" is an ultrasound sign detectable with ultrasound chest instruments; this sign consists of multiple comet-tails fanning out from the lung surface. They originate from water-thickened interlobular septa and would be ideal for nonradiologic bedside assessment of extravascular lung water. To assess the feasibility and value of ultrasonic comet signs, we studied 121 consecutive hospitalized patients (43 women and 78 men; aged 67 +/- 12 years) admitted to our combined cardiology-pneumology department (including cardiac intensive care unit); the study was conducted with commercially available echocardiographic systems including a portable unit. Transducer frequencies (range 2.5 to 3.5 MHz) were used. In each patient, the right and left chest was scanned by examining predefined locations in multiple intercostal spaces. Examiners blinded to clinical diagnoses noted the presence and numbers of lung comets at each examining site. A patient lung comet score was obtained by summing the number of comets in each of the scanning spaces. Within a few minutes, patients underwent chest x-ray, with specific assessment of extravascular lung water score by 2 pneumologist-radiologists blinded to clinical and echo findings. The chest ultrasound scan was obtained in all patients (feasibility 100%). The imaging time per examination was always <3 minutes. There was a linear correlation between echocardiographic comet score and radiologic lung water score (r = 0.78, p <0.01). Intrapatient variations (n = 15) showed an even stronger correlation between changes in echocardiographic lung comet and radiologic lung water scores (r = 0.89; p <0.01). In 121 consecutive hospitalized patients, we found a linear correlation between echocardiographic comet scores and radiologic extravascular lung water scores. Thus, the comet-tail is a simple, non-time-consuming, and reasonably accurate chest ultrasound sign of extravascular lung water that can be obtained at bedside (also with portable echocardiographic equipment) and is not restricted by cardiac acoustic window limitations.

Aged↗
PubMed2004

Clinical experience with axillary presentation breast cancer.

We present our experience of 50 cases of occult primary tumours presenting as axillary metastases, all with histological report of adenocarcinoma compatible with mammary carcinoma. After bilateral US and mammography, with MRI and mammoscintigraphy where necessary, ipsilateral breast cancer was suspected in 23 cases and quadrantectomy performed. Breast cancer was found only in 12 (24%). In the other 27 women there was no clinical or instrumental suspicion of breast cancer or other primary disease site, so the main treatment was complete axillary dissection plus radiotherapy to the ipsilateral breast (given to all patients). Chemotherapy alone was given to 27 patients, hormone treatment to 5 patients, and both to 18. Mean follow-up is 41.3 months (range 108-1). Thirty-nine (84%) patients are alive with no evidence of disease, two are alive with breast disease, five patients have died of metastatic disease (with no evidence breast disease). Our experience, like that of the literature, confirms that the breast should be extensively investigated but that blanket investigations are not usually revealing. We present guidelines for the work-up of patients presenting with axillary disease.

Antineoplastic Agents, Hormonal↗
PubMed2004

Less aggressive surgery and radiotherapy is the way forward.

PURPOSE OF REVIEW: Conserving the breast is one of the main objectives in treating patients affected by carcinoma. This objective should be compatible with good local control to keep the risk of local failures low. The progressive reduction of the extension of surgery in the breast and in the axilla is now accompanied by a reduction of the radiation field. This article provides an update on conservative therapy for breast cancer. RECENT FINDINGS: After the development of quadrantectomy, the effectiveness of sentinel node biopsy was demonstrated in the axillary staging of breast carcinoma. The situation took another step forward with partial breast irradiation. The highest incidence of local relapse after breast-conserving surgery is observed in the same area as the primary tumor. This factor provides the rationale for reducing the radiation field to a limited area of the breast primarily affected by carcinoma. SUMMARY: The Milan I trial on breast conservative surgery provided definitive confirmation of the equivalence of quadrantectomy, followed by radiotherapy, to mastectomy in terms of local control of disease. The randomized trial on sentinel node biopsy demonstrated the effectiveness of this procedure in axillary staging of breast carcinoma. Radiotherapy is currently under investigation in terms of limiting the radiation field to the affected quadrant of the breast by means of various techniques.

Breast Neoplasms↗
PubMed2004

Low triiodothyronine (T3) state: a predictor of outcome in respiratory failure? Results of a clinical pilot study.

BACKGROUND AND AIM: Various low triiodothyronine (T3) states have been described in severe nonthyroidal diseases and associated with a poor prognosis in cardiovascular disease patients. We assessed thyroid function in patients with severe respiratory failure from pulmonary disorders, and needing invasive or noninvasive mechanical ventilation, in order to evaluate the prognostic value of nonthyroidal illness syndrome. METHODS: We studied 32 consecutive patients with acute or acute-on-chronic respiratory failure. Measured variables upon admission included APACHE II score, the ratio of the partial pressure of oxygen in arterial blood to the fraction of oxygen in inspired gas (PaO(2)/FiO(2)), and plasma levels of free T3 (fT3) and free thyroxine (fT4), and TSH levels. Thyroid function was further evaluated at discharge. RESULTS: Plasma levels of fT3 were below normal in 17 patients (53%). Plasma fT3 was correlated with PaO(2)/FiO(2) (P<0.001), and with APACHE II score (P=0.003). In four patients (12.5%) who died, fT3 levels were significantly lower (P=0.002) than in patients who survived. In univariate logistic regression analysis, fT3 was the only factor significantly associated with an increased risk of death (odds ratio, 64.23; 95% confidence interval, 1.78-2316.86, P=0.023). Normalization of thyroid function was observed at discharge with a significant correlation between the percent increase in both fT3 and PaO(2)/FiO(2) (P=0.015). P values were calculated using Spearman's Correlation Coefficient. CONCLUSION: Our preliminary data suggest that the low T3 state is a predictor of outcome in pulmonary patients with respiratory failure.

Acute Disease↗
PubMed2003

A diagnostic strategy for pulmonary embolism based on standardised pretest probability and perfusion lung scanning: a management study.

Pulmonary embolism remains a challenging diagnostic problem. We developed a simple diagnostic strategy based on combination of assessment of the pretest probability with perfusion lung scan results to reduce the need for pulmonary angiography. We studied 390 consecutive patients (78% in-patients) with suspected pulmonary embolism. The pretest probability was rated low (<10%), intermediate (>10%, < or =50%), moderately high (>50%, < or =90%) or high (>90%) according to a structured clinical model. Perfusion lung scans were independently assigned to one of four categories: normal; near-normal; abnormal, suggestive of pulmonary embolism (wedge-shaped perfusion defects); abnormal, not suggestive of pulmonary embolism (perfusion defects other than wedge shaped). Pulmonary embolism was diagnosed in patients with abnormal scans suggestive of pulmonary embolism and moderately high or high pretest probability. Patients with normal or near-normal scans and those with abnormal scans not suggestive of pulmonary embolism and low pretest probability were deemed not to have pulmonary embolism. All other patients were allocated to pulmonary angiography. Patients in whom pulmonary embolism was excluded were left untreated. All patients were followed up for 1 year. Pulmonary embolism was diagnosed non-invasively in 132 patients (34%), and excluded in 191 (49%). Pulmonary angiography was required in 67 patients (17%). The prevalence of pulmonary embolism was 41% ( n=160). Patients in whom pulmonary embolism was excluded had a thrombo-embolic risk of 0.4% (95% confidence interval: 0.0%-2.8%). Our strategy permitted a non-invasive diagnosis or exclusion of pulmonary embolism in 83% of the cases (95% confidence interval: 79%-86%), and appeared to be safe.

Adolescent↗
PubMed2003

A structured clinical model for predicting the probability of pulmonary embolism.

PURPOSE: To develop a structured model to predict the clinical probability of pulmonary embolism. METHODS: We studied 1,100 consecutive patients with suspected pulmonary embolism in whom a definite diagnosis had been established. We used logistic regression analysis to estimate the probability of pulmonary embolism based on patients' clinical characteristics; the probability was categorized as low (< or = 10%), intermediate (>10%, < or = 50%), moderately high (>50%, < or = 90%), or high (>90%). RESULTS: The overall prevalence of pulmonary embolism was 40% (n = 440). Ten characteristics were associated with an increased risk of pulmonary embolism (male sex, older age, history of thrombophlebitis, sudden-onset dyspnea, chest pain, hemoptysis, electrocardiographic signs of acute right ventricular overload, radiographic signs of oligemia, amputation of the hilar artery, and pulmonary consolidation suggestive of infarction), and five were associated with a decreased risk (prior cardiovascular or pulmonary disease, high fever, pulmonary consolidation other than infarction, and pulmonary edema on the chest radiograph). With this model, 432 patients (39%) were rated a low probability, of whom 19 (4%) had pulmonary embolism; 283 (26%) were rated an intermediate probability, of whom 62 (22%) had pulmonary embolism; 72 (7%) were rated a moderately high probability, of whom 53 (74%) had pulmonary embolism; and 313 (28%) were rated a high probability, of whom 306 (98%) had pulmonary embolism. CONCLUSION: This prediction model may be useful for estimating the probability of pulmonary embolism before obtaining definitive test results.

Adolescent↗
PubMed2002

Airway inflammation in severe chronic obstructive pulmonary disease: relationship with lung function and radiologic emphysema.

The lung pathology of severe chronic obstructive pulmonary disease (COPD) has been poorly investigated. We examined surgical specimens obtained from patients with severe (forced expiratory volume in 1 second [FEV(1)] = 29 +/- 3% predicted, n = 9) or mild/no airflow limitation (FEV(1) = 86 +/- 5% predicted, n = 9) and similar smoking history. With histochemical and immunohistochemical methods we quantified the structural changes and the inflammatory cells in small airways and in muscular pulmonary arteries. As compared with smokers with mild/no COPD, smokers with severe COPD had an increased number of leukocytes in the small airways, which showed a positive correlation with the radiologic score of emphysema and with the value of residual volume, and a negative correlation with the values of FEV(1) and carbon monoxide diffusing capacity. The inflammatory process was characterized by an increase in CD8(+) and CD4(+) T-lymphocytes in the airway wall and by an increase in macrophages in the airway epithelium. When all smokers were considered together, the smoking history was correlated with both the airway wall and smooth muscle thickness, suggesting that smoking itself may play a role in the development of structural changes. No structural and cellular differences were observed in pulmonary arteries between smokers with severe COPD and smokers with mild/no COPD. In conclusion, in the small airways of smokers with severe COPD, there is an increased number of leukocytes, which is correlated with reduced expiratory flow, lung hyperinflation, carbon monoxide diffusion impairment, and radiologic emphysema, suggesting a role for this inflammatory response in the clinical progression of the disease.

Case-Control Studies↗
PubMed2002

Urinary desmosine excretion is inversely correlated with the extent of emphysema in patients with chronic obstructive pulmonary disease.

An enhanced proteolysis of lung interstitium is key event in the pathogenesis of emphysema, a major constituent of chronic obstructive pulmonary disease. To assess whether urinary desmosine and/or hydroxyproline may be used as a marker of lung destruction we studied urinary excretions of these products in 20 patients with chronic obstructive pulmonary disease and in 19 appropriate controls in 24h urine collection samples. For desmosine measurements, we developed a new indirect competitive enzyme-linked immunosorbent assay. The extent of emphysema was measured in high resolution computed tomography (CT) scans, by considering lung area with CT numbers <-950 Hounsfield units (HU). Urinary desmosine excretion was significantly higher in patients with chronic obstructive pulmonary disease than in controls (294+/-121 microg versus 183+/-93 microg, P=0.003), and was unrelated with both age and smoking habits. In patients with no evidence or only mild emphysema, desmosine excretion values were significantly higher (P=0.006) than those of patients with moderate to severe emphysema. In patients with chronic obstructive pulmonary disease, urinary hydroxyproline excretion was positively correlated with urinary desmosine excretion but on the average, it was not different from that of controls. These data indicate that urinary desmosine is a sensitive biological marker of lung elastin catabolism. The relatively low levels of urinary desmosine observed in patients with severe emphysema may be accounted for a decrease in elastin catabolism due to reduced lung elastin mass. Urinary desmosine may be used to identify subjects at risk of developing emphysema and to assess the efficacy of therapeutic interventions.

Adult↗
PubMed2002

[Transthoracic echocardiography in the diagnosis of pulmonary embolism].

Transthoracic echocardiography is advocated by some as a useful diagnostic test for patients with suspected pulmonary embolism (PE), but its diagnostic accuracy is unknown. Recently, the sensitivity and specificity of transthoracic echocardiography in the diagnosis of PE was determined prospectively in unselected patients using pulmonary angiography as a reference diagnostic standard. Echocardiographic criteria for diagnosing PE included the presence of any two of three abnormalities: right ventricular (RV) end-diastolic diameter > 27 mm (without RV wall hypertrophy), tricuspid regurgitation velocity > 2.7 m/s, or RV hypokinesis. These echocardiographic diagnostic criteria for PE yielded a sensitivity of 56% and a specificity of 90%. Because of its inherent poor sensitivity, transthoracic echocardiography should not be used as a routine test to screen patients for suspected PE.

Angiography↗
PubMed2000

Sentinel Node Biopsy Interpretation: The Milan Experience.

From March 1996 to December 1999 we performed 1,266 sentinel node biopsies (SNBs) in patients with small breast cancers. The technique is to inject technetium 99m-labeled albumin particles close to the tumor, locate the sentinel node (SN) scintigraphically, and use a handheld gamma-detecting probe to guide its removal via a small incision during breast surgery. Our experience was divided into three phases. In the first phase, complete axillary dissection was performed to assess the accuracy of SNB in predicting axillary status. We also assessed safety, perfected tracer injection technique, determined optimal particle size and radioactivity levels, optimized lymphoscintigraphic scanning, and perfected the surgical technique. The SN was identified and removed in 98.7% of cases. Comparison with complete axillary dissection showed that the SN predicted axillary status in 96.8% of cases. However, use of an intraoperative frozen section method predicted axillary status in only 86.5% of cases. In the second phase we developed a new method for intraoperative histologic analysis. Extensive sampling (up to 60 sections/SN) and an experienced pathologist proved more important than use of antikeratin immunostaining in identifying tumor cells, and the new method has the accuracy of a definitive histologic examination. The third phase, a randomized trial, closed at the end of 1999. Trial objectives were to confirm that the SN predicts axillary status, to determine the number of axillary relapses, and to assess overall and disease-free survival. Patients were randomized in the operating room to complete axillary dissection or SNB. If the SN was positive, complete axillary dissection was performed; if the SN was negative, no further axillary treatment was given. We expect the trial to confirm our clinical experience that SNB is a safe and accurate procedure for staging patients with early breast cancer and a clinically negative axilla.

Journal Article↗