Simonetta Monti - Academia.edu (original) (raw)
Papers by Simonetta Monti
Breast cancer research and treatment, Jan 1, 2004
We present our experience of 50 cases of occult primary tumours presenting as axillary metastases... more 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.
![Research paper thumbnail of [Transthoracic echocardiography in the diagnosis of pulmonary embolism]](https://attachments.academia-assets.com/39673606/thumbnails/1.jpg)
](Recenti progressi in medicina
Echocardiography is advocated by some as a useful diagnostic test for patients with suspected pul... more Echocardiography is advocated by some as a useful diagnostic test for patients with suspected pulmonary embolism (PE), but its diagnostic accuracy is unknown. The present study was undertaken to determine prospectively the sensitivity and specificity of transthoracic echocardiography in the diagnosis of PE.
Applied cardiopulmonary pathophysiology: ACP
ARDS is still characterized by an exceedingly high mortality rate. Methods are then needed to det... more ARDS is still characterized by an exceedingly high mortality rate. Methods are then needed to detect ARDS at the earliest clinical stage. Over the last decade, radioisotopic techniques have developed, aimed at demonstrating an abnormal neutrophil sequestration in the lung or detecting functional alterations of the pulmonary alveolar-capillary barrier, which likely precede the onset of respiratory distress. Preliminary application of these techniques in patients with ARDS yielded conflicting results in terms of sensitivity and specificity. On the contrary, lung vascular abnormalities have been consistently observed in patients with ARDS studied by perfusion lung scanning. They consist of focal, non segmental perfusion defects, mostly peripheral and dorsal, with redistribution of blood flow to non-dependent lung regions. This scintigraphic pattern may be considered typical of ARDS since it is not observed in other acute lung disorders. Perfusion abnormalities on lung scans are detectable from the very early stage of ARDS and correlate with the severity of the syndrome as reflected by gas exchange, central hemodynamics, and chest radiography. Perfusion lung scanning may then be used in the early detection and evaluation of vascular injury in ARDS.
The International Journal of Biochemistry & Cell Biology
An enhanced proteolysis of lung interstitium is key event in the pathogenesis of emphysema, a maj... more 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 value...
Internal and emergency medicine, 2009
Tumori
Although some guidelines recommend adjuvant radiotherapy (RT) to the axilla and supraclavicular n... more Although some guidelines recommend adjuvant radiotherapy (RT) to the axilla and supraclavicular nodes if 4 or more axillary nodes are involved, the current practice at our Institute is not to irradiate the axilla but to perform complete axillary dissection in which all 3 Berg levels are removed. We performed a retrospective analysis of patients with 4 or more axillary nodes involved and sufficient follow-up to provide indications as to whether our current treatment is adequate. We retrospectively analyzed 287 T1-T3 patients with a median follow-up of 5 years and 4 or more involved nodes treated by quadrantectomy and breast RT but no axillary RT; supraclavicular RT was given only when prognostic factors were unfavorable. A total of 170 (59.2%) patients did not receive supraclavicular RT, while 117 (40.8%) patients received supraclavicular irradiation. No patient received axillary RT. After a median follow-up of 5 years (range, 4-105 months), 4.7% had died and 13.5% had developed dist...
Critical care (London, England), 1999
OBJECTIVE: To assess the value of parameters derived from arterial blood gas tests in the diagnos... more OBJECTIVE: To assess the value of parameters derived from arterial blood gas tests in the diagnosis of pulmonary embolism. METHOD: We measured alveolar-arterial partial pressure of oxygen [P(A-a)O2] gradient, PaO2 and arterial partial pressure of carbon diaxide (PaCO2) in 773 consecutive patients with suspected pulmonary embolism who were enrolled in the Prospective Investigative Study of Acute Pulmonary Embolism. DIAGNOSIS: The study design required pulmonary angiography in all patients with abnormal perfusion scans. RESULTS: Of 773 scans, 270 were classified as normal/near-normal and 503 as abnormal. Pulmonary embolism was diagnosed by pulmonary angiography in 312 of 503 patients with abnormal scans. Of 312 patients with pulmonary embolism, 12, 14 and 35% had normal P(A-a)O2, PaO2 and PaCO2, respectively. Of 191 patients with abnormal scans and negative angiograms, 11, 13 and 55% had normal P(A-a)O2, PaO2 and PaCO2, respectively. The proportions of patients with normal/near-normal...
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 1997
Vinorelbine, is an active drug in the treatment of metastatic breast cancer and has a favorable t... more Vinorelbine, is an active drug in the treatment of metastatic breast cancer and has a favorable toxicity profile. Its combination with other effective and well-tolerated cytotoxics may thus be beneficial. We investigated the therapeutic effect of a combination of vinorelbine plus 5-fluorouracil and folinic acid as first-line treatment in patients with metastatic breast cancer. Forty-five patients with advanced or metastatic breast cancer were enrolled in this phase I-II study and treated with 5-fluorouracil (350 mg/m2 i.v. on day 1 to 3), folinic acid (100 mg/m2 i.v. on day 1 to 3) and vinorelbine given on days 1 and 3 at the dose of 25 mg/m2 (dose level 1), or 30 mg/m2 (dose level 2). Therapy was given on an outpatient basis every three weeks. Phase I: Dose limiting toxicity (DLT) occurred at the second dose level of vinorelbine (30 mg/m2), with two out of three patients developing severe constipation ('ileus-like syndrome' grade 4), and fever (grade 2). Consequently, the d...
Mitochondria act as a reservoir for the basic amine HIPDM in the lung. M. Miniati, A. Paci, F. Co... more Mitochondria act as a reservoir for the basic amine HIPDM in the lung. M. Miniati, A. Paci, F. Cocci, G. Ciarimboli, S. Monti, M. Pistolesi. ©ERS Journals Ltd 1996. ABSTRACT: The lungs are a site for the uptake, accumulation, and storage of exogenous basic amines. The compound N-N-N''-trimethyl-N''-(2-hydroxy-3-methyl- 5-iodobenzyl)-1,3 propanediamine (HIPDM) is a basic amine that can be labelled with radioactive iodine and detected by external counting. Intravenously injected 123I-HIPDM is extracted by the human lung, where it is retained in a slowly efflux- able pool. In the present study, we measured HIPDM lung kinetics and subcellular distri- bution in rabbits given i.v. 125I-HIPDM. Rabbits were killed from 2 min to 5 h after injection, and the radioactivity retained in their lungs was measured. Subcellular lung fractions (nuclear, mitochondrial, lysosomal, microsomal, and postmicroso- mal supernatant) were assayed for HIPDM radioactivity, protein content, and di...
The FASEB Journal
The basic compound iodobenzyl-propanediamine (HIPDM), when given intravenously, is extracted by t... more The basic compound iodobenzyl-propanediamine (HIPDM), when given intravenously, is extracted by the lungs whence it is effluxed at a slow exponential rate. In humans (normal non smokers), the mean residence time ({bar t}) of 123I-HIPDM, assessed by external detection, averages 7.2 {plus minus} 1.1 hrs. Persistence of HIPDM in lungs is significantly increased in asymptomatic smokers and, to a greater extent, in patients with ARDS. Since production of free oxygen radicals reportedly occurs as a consequence of smoke exposure and in the course of acute lung injury, the authors hypothesized that the prolonged persistence of HIPDM in the lungs of smokers and of patients with ARDS might reflect a peroxidative damage of lung tissue. They tested this hypothesis in rabbits since their baseline HIPDM lung clearance is similar to that of nonsmoking humans. In rabbits, acute lung injury was induced by phorbol myristate acetate. Three hrs after PMA administration, the animals received an i.v. bol...
Respiratory research
The receptor for advanced glycation end products (RAGE) is a multiligand signal transduction rece... more The receptor for advanced glycation end products (RAGE) is a multiligand signal transduction receptor that can initiate and perpetuate inflammation. Its soluble isoform (sRAGE) acts as a decoy receptor for RAGE ligands, and is thought to afford protection against inflammation. With the present study, we aimed at determining whether circulating sRAGE is correlated with emphysema and chronic cor pulmonale in chronic obstructive pulmonary disease (COPD). In 200 COPD patients and 201 age- and sex-matched controls, we measured lung function by spirometry, and sRAGE by ELISA method. We also measured the plasma levels of two RAGE ligands, N-epsilon-carboxymethyl lysine and S100A12, by ELISA method. In the COPD patients, we assessed the prevalence and severity of emphysema by computed tomography (CT), and the prevalence of chronic cor pulmonale by echocardiography. Multiple quantile regression was used to assess the effects of emphysema, chronic cor pulmonale, smoking history, and comorbid ...
Internal and Emergency Medicine, 2011
To establish whether C-reactive protein (CRP) is an independent predictor of all-cause mortality ... more To establish whether C-reactive protein (CRP) is an independent predictor of all-cause mortality and hospitalization in chronic obstructive pulmonary disease (COPD), we followed 200 patients with COPD and 201 age-and gender -matched controls for a median time of 4.2 years (range, 0.2-5.1 years). Airflow obstruction was rated moderate if forced expiratory volume in one second (FEV 1 ) was 50-69% of the predicted value, or severe if FEV 1 was \50%. The CRP level was categorized as low (B3 mg/L) or high ([3 mg/L). The hazard of death was estimated by a proportional hazard regression model, using controls with low CRP as the reference category. Fifty subjects died: 41 (21%) among the COPD and 9 (4%) among the controls (p \ 0.0001). The hazard of death in moderate COPD was not significantly higher than in the reference category, independently of the CRP level. In severe COPD with a low CRP, the hazard of death is 3.4 times higher than in the reference category (p = 0.008); in severe COPD and a high CRP it is 9.6 times higher (p \ 0.0001). The rate of hospitalization in COPD patients with a high CRP is 1.9 times higher than in those with a low CRP [95% confidence interval (CI), 1.2-3.2]. In severe COPD, it is 6.9 times higher than in moderate COPD (95% CI, 3.8-12.7). A high CRP level is a significant amplifier of the risk of death only in severe COPD. The degree of airflow obstruction is a strong independent predictor of COPD-related outcomes.
Medicine, 2014
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in indus... more Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in industrialized countries. Recent studies investigated the impact of comorbidities on the survival in COPD, but most of them lacked a referent group of comorbidity-matched, nonobstructed individuals.
Intraepithelial Neoplasia, 2012
Thrombosis Research, 2014
Objective: To assess the accuracy of chest radiography (CXR) in predicting pulmonary hypertension... more Objective: To assess the accuracy of chest radiography (CXR) in predicting pulmonary hypertension (PH). Methods: We studied 108 consecutive patients with suspected PH who underwent right heart catheterization (RHC). All were PH treatment naives. Hemodynamic criteria included a mean pulmonary artery pressure N 25 mmHg at rest, and a mean pulmonary wedge pressure b 15 mmHg. Postero-anterior and lateral CXR were obtained shortly before RHC. To avoid a selection bias which could be introduced by examining only patients with suspected PH, we included in the analysis the CXR of 454 additional patients with different diagnosis: 57 with left heart failure (LHF) and pulmonary venous hypertension at RHC, 197 with chronic obstructive pulmonary disease, and 200 non-obstructed controls. CXR were examined independently by 4 raters, who were blinded to clinical, hemodynamic, and spirometric data. The diagnosis of PH was made if a prominent main pulmonary artery was associated with anyone of: isolated enlargement of right ventricle, right descending pulmonary artery N 16 mm in diameter, pruning of peripheral pulmonary vessels. Results: Eighty-two patients had PH confirmed at RHC. Weighted sensitivity of CXR was 96.9% (95% confidence interval, 94.9 to 98.2%), and weighted specificity 99.8% (95% confidence interval, 99.6 to 99.9%). By considering the 165 patients who underwent RHC, weighted sensitivity of CXR was unchanged, and weighted specificity decreased to 99.1%. None of the patients with PH were misclassified as having LHF, and vice versa. Conclusions: CXR is accurate in predicting PH. It may aid clinicians in selecting patients with suspected PH for hemodynamic ascertainment.
Internal and Emergency Medicine, 2011
Patients with inoperable chronic thromboembolic pulmonary hypertension (Inop-CTEPH) treated with ... more Patients with inoperable chronic thromboembolic pulmonary hypertension (Inop-CTEPH) treated with conventional therapy have a poor survival. We compare the 3-year survival between those treated with conventional therapy and those treated with conventional therapy and a combination of novel drugs. We also evaluate the clinical course. A total of 34 Inop-CTEPH consecutive patients were evaluated from 1991 to 2009 including right heart catheterization (RHC) and perfusion lung scan (PLS): 7 underwent surgical treatment while 27 were confirmed inoperable. Of these 27 patients, 12 evaluated from 1991 to 2003 (Group 1) were treated with conventional therapy and 15 evaluated from 2004 to 2009 (Group 2) were treated with conventional and novel therapies. At baseline, no group difference emerged at RHC. Based on clinical course, novel drugs and oxygen supplementation were given to patients of Group 2. Seven of these who had worse clinical course repeated RHC and four of them also PLS during therapy. Those without repeat RHC had baseline pulmonary artery mean pressure and brain natriuretic peptide (NT-proBNP) lower and mixed venous saturation (SvO2) and exercise test higher (p = 0.022, 0.015, 0.044 and 0.003, respectively). During therapy, those with repeat RHC had total pulmonary vascular resistance reduced (p = 0.012), base excess increased (p = 0.002) and significant redistribution of pulmonary blood flow at PLS. At the 3-year follow-up, survival was 86% in Group 2 and 31% in Group 1 (p = 0.031). In Inop-CTEPH patients, the clinical course may help to select drugs and the level of oxygen supply that can improve hemodynamics, gas exchange and long-term survival.
Medicine, 2006
We followed prospectively 834 consecutive patients (70% inpatients), evaluated for suspected pulm... more 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.
Breast cancer research and treatment, Jan 1, 2004
We present our experience of 50 cases of occult primary tumours presenting as axillary metastases... more 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.
Recenti progressi in medicina
Echocardiography is advocated by some as a useful diagnostic test for patients with suspected pul... more Echocardiography is advocated by some as a useful diagnostic test for patients with suspected pulmonary embolism (PE), but its diagnostic accuracy is unknown. The present study was undertaken to determine prospectively the sensitivity and specificity of transthoracic echocardiography in the diagnosis of PE.
Applied cardiopulmonary pathophysiology: ACP
ARDS is still characterized by an exceedingly high mortality rate. Methods are then needed to det... more ARDS is still characterized by an exceedingly high mortality rate. Methods are then needed to detect ARDS at the earliest clinical stage. Over the last decade, radioisotopic techniques have developed, aimed at demonstrating an abnormal neutrophil sequestration in the lung or detecting functional alterations of the pulmonary alveolar-capillary barrier, which likely precede the onset of respiratory distress. Preliminary application of these techniques in patients with ARDS yielded conflicting results in terms of sensitivity and specificity. On the contrary, lung vascular abnormalities have been consistently observed in patients with ARDS studied by perfusion lung scanning. They consist of focal, non segmental perfusion defects, mostly peripheral and dorsal, with redistribution of blood flow to non-dependent lung regions. This scintigraphic pattern may be considered typical of ARDS since it is not observed in other acute lung disorders. Perfusion abnormalities on lung scans are detectable from the very early stage of ARDS and correlate with the severity of the syndrome as reflected by gas exchange, central hemodynamics, and chest radiography. Perfusion lung scanning may then be used in the early detection and evaluation of vascular injury in ARDS.
The International Journal of Biochemistry & Cell Biology
An enhanced proteolysis of lung interstitium is key event in the pathogenesis of emphysema, a maj... more 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 value...
Internal and emergency medicine, 2009
Tumori
Although some guidelines recommend adjuvant radiotherapy (RT) to the axilla and supraclavicular n... more Although some guidelines recommend adjuvant radiotherapy (RT) to the axilla and supraclavicular nodes if 4 or more axillary nodes are involved, the current practice at our Institute is not to irradiate the axilla but to perform complete axillary dissection in which all 3 Berg levels are removed. We performed a retrospective analysis of patients with 4 or more axillary nodes involved and sufficient follow-up to provide indications as to whether our current treatment is adequate. We retrospectively analyzed 287 T1-T3 patients with a median follow-up of 5 years and 4 or more involved nodes treated by quadrantectomy and breast RT but no axillary RT; supraclavicular RT was given only when prognostic factors were unfavorable. A total of 170 (59.2%) patients did not receive supraclavicular RT, while 117 (40.8%) patients received supraclavicular irradiation. No patient received axillary RT. After a median follow-up of 5 years (range, 4-105 months), 4.7% had died and 13.5% had developed dist...
Critical care (London, England), 1999
OBJECTIVE: To assess the value of parameters derived from arterial blood gas tests in the diagnos... more OBJECTIVE: To assess the value of parameters derived from arterial blood gas tests in the diagnosis of pulmonary embolism. METHOD: We measured alveolar-arterial partial pressure of oxygen [P(A-a)O2] gradient, PaO2 and arterial partial pressure of carbon diaxide (PaCO2) in 773 consecutive patients with suspected pulmonary embolism who were enrolled in the Prospective Investigative Study of Acute Pulmonary Embolism. DIAGNOSIS: The study design required pulmonary angiography in all patients with abnormal perfusion scans. RESULTS: Of 773 scans, 270 were classified as normal/near-normal and 503 as abnormal. Pulmonary embolism was diagnosed by pulmonary angiography in 312 of 503 patients with abnormal scans. Of 312 patients with pulmonary embolism, 12, 14 and 35% had normal P(A-a)O2, PaO2 and PaCO2, respectively. Of 191 patients with abnormal scans and negative angiograms, 11, 13 and 55% had normal P(A-a)O2, PaO2 and PaCO2, respectively. The proportions of patients with normal/near-normal...
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 1997
Vinorelbine, is an active drug in the treatment of metastatic breast cancer and has a favorable t... more Vinorelbine, is an active drug in the treatment of metastatic breast cancer and has a favorable toxicity profile. Its combination with other effective and well-tolerated cytotoxics may thus be beneficial. We investigated the therapeutic effect of a combination of vinorelbine plus 5-fluorouracil and folinic acid as first-line treatment in patients with metastatic breast cancer. Forty-five patients with advanced or metastatic breast cancer were enrolled in this phase I-II study and treated with 5-fluorouracil (350 mg/m2 i.v. on day 1 to 3), folinic acid (100 mg/m2 i.v. on day 1 to 3) and vinorelbine given on days 1 and 3 at the dose of 25 mg/m2 (dose level 1), or 30 mg/m2 (dose level 2). Therapy was given on an outpatient basis every three weeks. Phase I: Dose limiting toxicity (DLT) occurred at the second dose level of vinorelbine (30 mg/m2), with two out of three patients developing severe constipation ('ileus-like syndrome' grade 4), and fever (grade 2). Consequently, the d...
Mitochondria act as a reservoir for the basic amine HIPDM in the lung. M. Miniati, A. Paci, F. Co... more Mitochondria act as a reservoir for the basic amine HIPDM in the lung. M. Miniati, A. Paci, F. Cocci, G. Ciarimboli, S. Monti, M. Pistolesi. ©ERS Journals Ltd 1996. ABSTRACT: The lungs are a site for the uptake, accumulation, and storage of exogenous basic amines. The compound N-N-N''-trimethyl-N''-(2-hydroxy-3-methyl- 5-iodobenzyl)-1,3 propanediamine (HIPDM) is a basic amine that can be labelled with radioactive iodine and detected by external counting. Intravenously injected 123I-HIPDM is extracted by the human lung, where it is retained in a slowly efflux- able pool. In the present study, we measured HIPDM lung kinetics and subcellular distri- bution in rabbits given i.v. 125I-HIPDM. Rabbits were killed from 2 min to 5 h after injection, and the radioactivity retained in their lungs was measured. Subcellular lung fractions (nuclear, mitochondrial, lysosomal, microsomal, and postmicroso- mal supernatant) were assayed for HIPDM radioactivity, protein content, and di...
The FASEB Journal
The basic compound iodobenzyl-propanediamine (HIPDM), when given intravenously, is extracted by t... more The basic compound iodobenzyl-propanediamine (HIPDM), when given intravenously, is extracted by the lungs whence it is effluxed at a slow exponential rate. In humans (normal non smokers), the mean residence time ({bar t}) of 123I-HIPDM, assessed by external detection, averages 7.2 {plus minus} 1.1 hrs. Persistence of HIPDM in lungs is significantly increased in asymptomatic smokers and, to a greater extent, in patients with ARDS. Since production of free oxygen radicals reportedly occurs as a consequence of smoke exposure and in the course of acute lung injury, the authors hypothesized that the prolonged persistence of HIPDM in the lungs of smokers and of patients with ARDS might reflect a peroxidative damage of lung tissue. They tested this hypothesis in rabbits since their baseline HIPDM lung clearance is similar to that of nonsmoking humans. In rabbits, acute lung injury was induced by phorbol myristate acetate. Three hrs after PMA administration, the animals received an i.v. bol...
Respiratory research
The receptor for advanced glycation end products (RAGE) is a multiligand signal transduction rece... more The receptor for advanced glycation end products (RAGE) is a multiligand signal transduction receptor that can initiate and perpetuate inflammation. Its soluble isoform (sRAGE) acts as a decoy receptor for RAGE ligands, and is thought to afford protection against inflammation. With the present study, we aimed at determining whether circulating sRAGE is correlated with emphysema and chronic cor pulmonale in chronic obstructive pulmonary disease (COPD). In 200 COPD patients and 201 age- and sex-matched controls, we measured lung function by spirometry, and sRAGE by ELISA method. We also measured the plasma levels of two RAGE ligands, N-epsilon-carboxymethyl lysine and S100A12, by ELISA method. In the COPD patients, we assessed the prevalence and severity of emphysema by computed tomography (CT), and the prevalence of chronic cor pulmonale by echocardiography. Multiple quantile regression was used to assess the effects of emphysema, chronic cor pulmonale, smoking history, and comorbid ...
Internal and Emergency Medicine, 2011
To establish whether C-reactive protein (CRP) is an independent predictor of all-cause mortality ... more To establish whether C-reactive protein (CRP) is an independent predictor of all-cause mortality and hospitalization in chronic obstructive pulmonary disease (COPD), we followed 200 patients with COPD and 201 age-and gender -matched controls for a median time of 4.2 years (range, 0.2-5.1 years). Airflow obstruction was rated moderate if forced expiratory volume in one second (FEV 1 ) was 50-69% of the predicted value, or severe if FEV 1 was \50%. The CRP level was categorized as low (B3 mg/L) or high ([3 mg/L). The hazard of death was estimated by a proportional hazard regression model, using controls with low CRP as the reference category. Fifty subjects died: 41 (21%) among the COPD and 9 (4%) among the controls (p \ 0.0001). The hazard of death in moderate COPD was not significantly higher than in the reference category, independently of the CRP level. In severe COPD with a low CRP, the hazard of death is 3.4 times higher than in the reference category (p = 0.008); in severe COPD and a high CRP it is 9.6 times higher (p \ 0.0001). The rate of hospitalization in COPD patients with a high CRP is 1.9 times higher than in those with a low CRP [95% confidence interval (CI), 1.2-3.2]. In severe COPD, it is 6.9 times higher than in moderate COPD (95% CI, 3.8-12.7). A high CRP level is a significant amplifier of the risk of death only in severe COPD. The degree of airflow obstruction is a strong independent predictor of COPD-related outcomes.
Medicine, 2014
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in indus... more Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in industrialized countries. Recent studies investigated the impact of comorbidities on the survival in COPD, but most of them lacked a referent group of comorbidity-matched, nonobstructed individuals.
Intraepithelial Neoplasia, 2012
Thrombosis Research, 2014
Objective: To assess the accuracy of chest radiography (CXR) in predicting pulmonary hypertension... more Objective: To assess the accuracy of chest radiography (CXR) in predicting pulmonary hypertension (PH). Methods: We studied 108 consecutive patients with suspected PH who underwent right heart catheterization (RHC). All were PH treatment naives. Hemodynamic criteria included a mean pulmonary artery pressure N 25 mmHg at rest, and a mean pulmonary wedge pressure b 15 mmHg. Postero-anterior and lateral CXR were obtained shortly before RHC. To avoid a selection bias which could be introduced by examining only patients with suspected PH, we included in the analysis the CXR of 454 additional patients with different diagnosis: 57 with left heart failure (LHF) and pulmonary venous hypertension at RHC, 197 with chronic obstructive pulmonary disease, and 200 non-obstructed controls. CXR were examined independently by 4 raters, who were blinded to clinical, hemodynamic, and spirometric data. The diagnosis of PH was made if a prominent main pulmonary artery was associated with anyone of: isolated enlargement of right ventricle, right descending pulmonary artery N 16 mm in diameter, pruning of peripheral pulmonary vessels. Results: Eighty-two patients had PH confirmed at RHC. Weighted sensitivity of CXR was 96.9% (95% confidence interval, 94.9 to 98.2%), and weighted specificity 99.8% (95% confidence interval, 99.6 to 99.9%). By considering the 165 patients who underwent RHC, weighted sensitivity of CXR was unchanged, and weighted specificity decreased to 99.1%. None of the patients with PH were misclassified as having LHF, and vice versa. Conclusions: CXR is accurate in predicting PH. It may aid clinicians in selecting patients with suspected PH for hemodynamic ascertainment.
Internal and Emergency Medicine, 2011
Patients with inoperable chronic thromboembolic pulmonary hypertension (Inop-CTEPH) treated with ... more Patients with inoperable chronic thromboembolic pulmonary hypertension (Inop-CTEPH) treated with conventional therapy have a poor survival. We compare the 3-year survival between those treated with conventional therapy and those treated with conventional therapy and a combination of novel drugs. We also evaluate the clinical course. A total of 34 Inop-CTEPH consecutive patients were evaluated from 1991 to 2009 including right heart catheterization (RHC) and perfusion lung scan (PLS): 7 underwent surgical treatment while 27 were confirmed inoperable. Of these 27 patients, 12 evaluated from 1991 to 2003 (Group 1) were treated with conventional therapy and 15 evaluated from 2004 to 2009 (Group 2) were treated with conventional and novel therapies. At baseline, no group difference emerged at RHC. Based on clinical course, novel drugs and oxygen supplementation were given to patients of Group 2. Seven of these who had worse clinical course repeated RHC and four of them also PLS during therapy. Those without repeat RHC had baseline pulmonary artery mean pressure and brain natriuretic peptide (NT-proBNP) lower and mixed venous saturation (SvO2) and exercise test higher (p = 0.022, 0.015, 0.044 and 0.003, respectively). During therapy, those with repeat RHC had total pulmonary vascular resistance reduced (p = 0.012), base excess increased (p = 0.002) and significant redistribution of pulmonary blood flow at PLS. At the 3-year follow-up, survival was 86% in Group 2 and 31% in Group 1 (p = 0.031). In Inop-CTEPH patients, the clinical course may help to select drugs and the level of oxygen supply that can improve hemodynamics, gas exchange and long-term survival.
Medicine, 2006
We followed prospectively 834 consecutive patients (70% inpatients), evaluated for suspected pulm... more 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.