Mesothelioma: Scherpereel A

Scherpereel A, Anonymous00398. · INSERM Unit 774, Institut Pasteur de Lille, France. · Respir Med. · Pubmed #17137779 No free full text.

Abstract: Previously considered as a rare tumor, malignant pleural mesothelioma (MPM) has become a very important public health issue. In fact, MPM is a tumor with a poor survival, and its incidence is expected to continue to increase for at least the next 10 years. Asbestos exposure is the main factor involved in MPM pathogenesis. The diagnosis of MPM may be difficult because of differential diagnosis such as pleural benign disease induced by asbestos exposure or pleural metastasis of adenocarcinoma. Management of patients with MPM also remains complicated because they are often referred for evaluation late in the evolution of the disease. Moreover, MPM exhibits a high resistance to radiotherapy and chemotherapy; only few patients are candidates for radical surgery. New therapeutic strategies such as gene or cell therapy are still on clinical trial. Therefore, an optimal treatment of MPM is not clearly defined yet, despite the introduction of recent drugs. Between April 2005 and January 2006, the French Speaking Society for Chest Medicine (SPLF), in collaboration with other French scientific societies, brought together experts on mesothelioma to draw up recommendations in order to provide clinicians with clear, concise, up-to-date guidelines on management of MPM, presented in this report.

Scherpereel A. · No affiliation provided · Rev Mal Respir. · Pubmed #17370375 No free full text.

This publication has no abstract.

Grigoriu BD, Grégoire M, Chahine B, Scherpereel A. · Inserm U774, Institut Pasteur, Lille, France. · Bull Cancer. · Pubmed #18304902 No free full text.

Abstract: The increasing number of malignant pleural mesothelioma (MPM) is a serious public health problem. The prognosis of this tumor is poor and most of the patients are diagnosed late in the disease's course when curative treatment is no more an option. It is therefore necessary to diagnose earlier MPM in these patients in order to obtain a potential significant improvement in survival. Some serum markers have been previously proposed for MPM diagnosis but none had sufficient sensitivity and specificity for being use in routine. Recently, soluble mesothelin and osteopontin have been proposed as diagnostic markers for mesothelioma. The authors reviewed recent data concerning the utility of these two molecules in the diagnosis and the treatment of MPM. Mesothelin seems to be a specific marker for the epithelioid subtype of mesothelioma. Despite a good sensitivity, osteopontin has a low specificity for mesothelioma diagnosis. However, there is not enough data yet to propose guidelines on the use of these markers in a day to day practice.

Greillier L, Scherpereel A, Astoul P, Anonymous00352. · Département des Maladies Respiratoires, Unité d'Oncologie Thoracique, Hôpital Sainte-Marguerite, Marseille, France. · Rev Mal Respir. · Pubmed #18235408 No free full text.

Abstract: Realistic improvement has been recently done for the treatment of malignant pleural mesothelioma. Besides new findings for the epidemiology of the disease, medico-social impact for patients, the knowledge of biological parameters for diagnosis, prognosis and future therapeutic targets as well, the early diagnosis of the disease mainly based on more extended practice of thoracoscopy allows in association with new imaging techniques a careful staging of the disease and consequently new therapeutic implications. Indeed if new balistic assessment of the disease improves the efficacy of radiotherapy and new combined chemotherapy have shown antitumoral responses, surgical strategy takes part in the armamenterium for this disease and combined with others therapeutic modalities seems to be a raisonnable approach despite the lack of prospective, comparative, randomized study and the drawback of current staging. However, the most important point is the multidisciplinary concertation induced by the management of this disease which represents a "model" in thoracic oncology.

Scherpereel A, Lee YC. · Pulmonary and Thoracic Oncology Department, Hopital Calmette, Lille, France. · Curr Opin Pulm Med. · Pubmed #17534183 No free full text.

Abstract: PURPOSE OF REVIEW: Mesothelioma is an incurable cancer and its global incidence continues to increase. There has been strong interest in the search for a biomarker that would be of value for the diagnosis, prognosis and disease monitoring of mesothelioma. Large series evaluating the use of novel candidate markers have recently been published. RECENT FINDINGS: To date, global gene profiling studies have failed to find a molecule that reliably captures all subtypes of mesothelioma, and differentiates it from benign pathologies and metastatic carcinomas. Soluble mesothelin-related peptide (SMRP), osteopontin and megakaryocyte potentiating factor have been assessed as markers. SMRP testing is clinically available and provides reasonable diagnostic sensitivity and specificity when applied to serum or pleural fluid. Elevated SMRP levels can occur in metastatic, especially ovarian and pancreatic, adenocarcinomas. False negatives are common with sarcomatoid mesothelioma. SMRP levels may reflect tumor load and disease progression. The role of SMRP in predicting mesothelioma development in subjects exposed to asbestos has raised interest. Osteopontin lacks specificity as a diagnostic marker for mesothelioma but may have value in disease monitoring. SUMMARY: The proposed markers have insufficient accuracy to replace cytohistology as the gold standard for diagnosis for mesothelioma. Elevated SMRP levels raise suspicion of mesothelioma although negative values do not exclude disease. Its role in disease monitoring in patients and in predicting disease development in at-risk individuals warrant further study.

Grigoriu BD, Chahine B, Vachani A, Gey T, Conti M, Sterman DH, Marchandise G, Porte H, Albelda SM, Scherpereel A. · INSERM Unit 774, Institut Pasteur of Lille, Lille, France. · Am J Respir Crit Care Med. · Pubmed #19201924 No free full text.

Abstract: RATIONALE: Previous data suggested that serum levels of soluble mesothelin (SM) are related to tumor size and may have prognostic significance in malignant pleural mesothelioma (MPM). OBJECTIVES: We tested the hypothesis that this marker could also be useful for monitoring response to treatment. METHODS: Serial measurements of SM were determined in 40 patients diagnosed with MPM and subjected to gene-transfer therapy using intrapleural infusion of an adenoviral vector expressing human IFN-beta or conventional treatment (mainly chemotherapy). MEASUREMENTS AND MAIN RESULTS: In patients with baseline SM levels greater than 1 nM/L and disease progression after therapy, SM levels increased by 2.1 nM/L at two, 5.2 nM/L at four and 1.3 nM/L at 6 months. Patients with initial SM below 1 nM/L had a similar but more moderate increase of SM over time. Patients who responded to treatment or were considered stable had an initial small decrease of SM followed by a return to baseline values after 6 months of follow-up. In patients with baseline SM levels greater than 1 nM/L, increasing levels were associated with a significantly shorter median survival than in patients with stable or decreasing SM levels (4.4 vs. 27.7 months; P = 0.012). CONCLUSIONS: Increasing serum levels of SM were associated with disease progression and worse outcome, whereas stable or decreasing values suggested response to treatment. If confirmed in larger series, SM could be used to monitor patients with malignant pleural mesothelioma under treatment.

Grigoriu BD, Grigoriu C, Chahine B, Gey T, Scherpereel A. · INSERM, U774, Institut Pasteur de Lille, France. · Monaldi Arch Chest Dis. · Pubmed #19522163 No free full text.

Abstract: Malignant mesothelioma has a very dismal prognosis with very few patients surviving one year after diagnosis. Early multimodal treatment, however, is expected to improve the outcome. Today, there is a strong need to have disease markers which could be used for screening, diagnosing, and/or monitoring tumour response to treatment. Old markers such as hyaluronic acid, various cytokeratin fragments (CYFRA 21.1, TPA) and other cancer antigens (CA 15.3, CA 125 or CA 19.9 or CEA) are not sensitive or specific enough and cannot be used in practice. More recently new molecules, such as soluble mesothelin and osteopontin, have been proposed for diagnostic purposes. Soluble mesothelin has a good specificity but has a sub-optimal sensitivity being negative in all sarcomatoid and in up to one half of epithelioid mesothelioma. On the contrary osteopontin has an inadequate specificity. Combining different markers together does not lead to an improvement in diagnostic accuracy. Neither marker can be used for screening purposes, the main limitation being the very low incidence of the disease in the at-risk, asbestos exposed population. Mesothelin is also a promising marker for monitoring response to treatment but published data is still insufficient to make recommendations. There is still a strong need for research is this area both in order to discover new markers as well as to correct the positioning of each existing molecule (alone or in combination) is the evaluation of the patients with a mesothelioma.

Vandermeers F, Hubert P, Delvenne P, Mascaux C, Grigoriu B, Burny A, Scherpereel A, Willems L. · Molecular and Cellular Biology, Gembloux Agricultural University (FUSAG), Gembloux, Belgium. · Clin Cancer Res. · Pubmed #19351772 No free full text.

Abstract: PURPOSE: Present chemotherapeutic regimens are marginally efficient in tumor cells being particularly resistant to radiotherapy and/or chemotherapy. We hypothesized that unresponsiveness of tumors to conventional therapeutic agents might be due to inappropriate gene expression resulting from epigenetic modifications and leading to transcriptional silencing. The goal of this study was to evaluate the anticancer effect of a histone deacetylase inhibitor, valproate, on mesothelioma cells in combination with pemetrexed and cisplatin, the usual first-line regimen of chemotherapy for this tumor. Experimental Design and RESULTS: We show that valproate augments apoptosis induced by pemetrexed and cisplatin in mesothelioma cell lines and in tumor cells from patient's biopsies. Onset of apoptosis involves both extrinsic and intrinsic pathways requiring enzymatic activities of caspases 8 and 9, respectively. Valproate but not suberoylanilide hydroxamic acid efficiently stimulates the production of reactive oxygen species. The free radical scavenger N-acetylcysteine inhibits apoptosis, indicating that reactive oxygen species are major mediators of valproate activity. As expected, valproate alone or combined with pemetrexed and cisplatin triggers hyperacetylation of histone H3. Bid protein processing in truncated t-Bid and cytochrome c release from mitochondria are significantly increased in the presence of valproate, providing a mechanistic rationale for improvement of the proapoptotic efficacy of cisplatin and pemetrexed. Finally, valproate when combined with pemetrexed and cisplatin prevents tumor growth in mouse models of epithelioid mesothelioma. CONCLUSIONS: These observations support the potential additional efficacy of valproate in combination with pemetrexed and cisplatin for treatment of malignant mesothelioma.

Grigoriu B, Chahine B, Zerimech F, Grégoire M, Balduyck M, Copin MC, Devos P, Lassalle P, Scherpereel A. · INSERM Unit 774, Institut Pasteur de Lille, Rue du Professeur Calmette, 59000 Lille, France. · Clin Biochem. · Pubmed #19302997 No free full text.

Abstract: We assessed comparatively the diagnostic value of two potential malignant pleural mesothelioma (MPM) markers: hyaluronic acid (HA) and soluble mesothelin. MATERIALS AND METHOD: We measured serum and pleural fluid values of mesothelin and hyaluronic acid in 76 patients with MPM, 33 patients with pleural metastases of carcinomas (Mets group) and 27 patients with benign pleural effusion related to asbestos exposure (BPLAE). RESULTS: Using a serum HA cut-off of 100 microg/L, 8 patients/33 (24.2%) were positive in the Mets group versus 20/76 (26.3%) in the MPM group and only 1/27 BPLAE patients. The area under ROC curve for serum HA in MPM versus Mets or BPLAE groups was only 0.617 while it was 0.755 for mesothelin. In pleural fluid, both markers had similar diagnostic values. CONCLUSIONS: Serum mesothelin is more sensitive than hyaluronic acid in diagnosing MPM and there is no benefit in combining both markers.

Scherpereel A, Grigoriu BD, Astoul P. · Service de Pneumologie et Oncologie Thoracique, Hôpital Calmette, CHRU de Lille, Lille, France. · Rev Mal Respir. · Pubmed #18971844 No free full text.

Abstract: Malignant pleural mesothelioma (MPM) is a serious issue worldwide because of its increasing incidence and poor prognosis despite real recent improvements in the disease management. Most of the patients are diagnosed late in the course of the disease when radical treatment is no more an option. Therefore an earlier diagnosis of MPM is needed to significantly increase the survival of patients. Some soluble markers, including soluble mesothelin and osteopontin, have been previously proposed for MPM diagnosis but none has been validated yet. Soluble mesothelin, assessed in blood and in pleural effusion, seems to be the most promising candidate. However, even if it has a good diagnostic and prognostic value, it is quite specific for the epithelioid subtype, the most frequent one of mesothelioma, thus limiting its usefulness in practice. Despite sometimes a good sensitivity, other potential markers as osteopontin are of little interest for MPM diagnosis because of a low specificity. In conclusion, the present data do not justify the use of biology for MPM diagnosis in routine yet but rather suggest a need for a continuing evaluation of soluble mesothelin in clinical studies and the search for other potential tumor markers.

Sapede C, Gauvrit A, Barbieux I, Padieu M, Cellerin L, Sagan C, Scherpereel A, Dabouis G, Grégoire M. · INSERM U601, Département de Recherche en Cancérologie, Institut de Biologie/CHU, 44093 Nantes, France. · Cancer Sci. · Pubmed #18167128 No free full text.

Abstract: Elevated amounts of soluble mesothelin-related proteins (SMRP) have already been reported in sera and pleural effusions from mesothelioma patients, providing a useful diagnostic marker for malignant pleural mesothelioma (MPM). However, the origin of SMRP is not yet understood. Production of SMRP could be related to abnormal splicing events leading to synthesis of a secreted protein (release) or to an enzymatic cleavage from membrane-bound mesothelin (ectodomain shedding). To test these hypotheses, we used a panel of mesothelioma cells established in culture from pleural effusions of MPM patients. Our in vitro results confirmed specific mesothelin expression and SMRP production in supernatants from epithelioid MPM cell lines, thus providing a relevant cellular model to study soluble mesothelin production mechanisms. The expression of mesothelin-encoding RNA variants was screened by reverse transcription-polymerase chain reaction experiments. Protease involvement in mesothelin cleavage from the cellular surface was investigated by treatment of MPM cells with GM6001, a broad-spectrum MMP- and ADAM-family inhibitor. GM6001 treatment significantly impaired SMRP production by MPM cell lines, in favor of an enzymatic-mediated shedding process. In addition, a splice variant transcript of mesothelin (variant 3) was detected in these MPM cell lines, in accordance with the release of a secreted part of the protein. Our results indicate that both mechanisms could be implicated in soluble mesothelin production by epithelioid mesothelioma cells.

Greillier L, Cavailles A, Fraticelli A, Scherpereel A, Barlesi F, Tassi G, Thomas P, Astoul P. · Division of Thoracic Oncology, Federation of Pulmonary Diseases and Thoracic Surgery, University of the Mediterranean Sea, Ste-Marguerite Hospital, Marseille, France. · Cancer. · Pubmed #17886249 links to  free full text

Abstract: BACKGROUND: Promising results with trimodality therapy combining surgery, chemotherapy, and radiotherapy have been obtained in the management of patients with malignant pleural mesothelioma (MPM). However, the histologic subtype has to be taken into account because of its influence on prognosis. The aim of the current study was to analyze retrospectively the accuracy, sensitivity, and specificity of preoperative thoracoscopy for diagnosis of the histologic subtype of MPM. METHODS: The histologic reports from all consecutive patients undergoing 'intent-to-treat' surgery from 3 institutions as well as the initial pathologic diagnosis obtained using thoracoscopy were reviewed and compared after institutional review board approval. All cases of MPM were confirmed by a panel of pathologists. RESULTS: Ninety-five patients were included in the current study. Of these 95 patients, 75 underwent extrapleural pneumonectomy, 9 patients underwent pleurectomy/decortication, and 11 patients underwent pleurectomy. Of the 95 patients with a final diagnosis of MPM, 80 (84.2%) were classified as having epithelial and 15 (15.8%) as having biphasic subtype. Among the 87 patients classified as having MPM of epithelial subtype after the initial thoracoscopy, 75 cases (86.2%) were confirmed to be a true histologic diagnosis and 12 cases (13.8%) were found to be of biphasic subtype at final diagnosis. One patient with a biphasic subtype at initial thoracoscopy was found to have MPM of epithelial subtype after surgery. The sensitivity and specificity values of an epithelial subtype diagnosis after thoracoscopy were 94% and 20%, respectively, with a positive predictive value of 86% and a negative predictive value of 37%. Conversely, the sensitivity and specificity values of a biphasic subtype diagnosis after thoracoscopy were 20% and 98%, respectively, with a positive predictive value of 75% and a negative predictive value of 87%. CONCLUSIONS: Pleural biopsy performed using thoracoscopy is considered to be the cornerstone of the diagnosis and pleural staging of MPM. However, this procedure appears to be less efficient in diagnosing the histologic subtype as either epithelial or biphasic.

Grigoriu BD, Scherpereel A, Devos P, Chahine B, Letourneux M, Lebailly P, Grégoire M, Porte H, Copin MC, Lassalle P. · Institut National de la Sante et de la Recherche Medicale (INSERM) U774, Institut Pasteur de Lille, Lille, France. · Clin Cancer Res. · Pubmed #17504993 links to  free full text

Abstract: PURPOSE: Malignant mesothelioma is a highly aggressive tumor and is often diagnosed too late for a curative treatment. We compared diagnostic and prognostic values of mesothelin and osteopontin in 172 patients suspected of malignant pleural mesothelioma (MPM) and in a control group of 112 asymptomatic asbestos-exposed subjects. EXPERIMENTAL DESIGN: Osteopontin and mesothelin were assayed with commercial ELISA kits in a series of 43 patients with pleural metastases of various carcinomas, 33 patients with benign pleural lesions associated with asbestos exposure, 96 patients with MPMs, and 112 asbestos-exposed healthy subjects. Results were correlated with patient's diagnosis and survival. RESULTS: Serum osteopontin level was higher in MPM patients compared with healthy asbestos-exposed subjects and had a good capability to distinguish between these two populations. However, osteopontin was unable to distinguish between MPM and pleural metastatic carcinoma or benign pleural lesions associated with asbestos exposure. Neither plasma nor pleural fluid osteopontin were more powerful in this respect. Serum mesothelin had a good ability for diagnosing MPM but was unable to identify patients with nonepithelioid mesothelioma subtypes. Survival analysis identified tumor histologic subtype along with serum osteopontin and serum mesothelin as independent prognostic factors in mesothelioma patients. CONCLUSIONS: Osteopontin has a lower diagnostic accuracy than mesothelin in patients suspected of MPM. Insufficient specificity limits osteopontin utility as diagnostic marker. Both molecules have a potential value as prognostic markers.

Scherpereel A, Grigoriu B, Conti M, Gey T, Grégoire M, Copin MC, Devos P, Chahine B, Porte H, Lassalle P. · INSERM Unit 774, Institut Pasteur de Lille, 59037 Lille Cedex, France. · Am J Respir Crit Care Med. · Pubmed #16456138 links to  free full text

Abstract: BACKGROUND: Diagnosis of malignant pleural mesothelioma is a challenging issue. Potential markers in mesothelioma diagnosis include soluble mesothelin-related peptides (SMRPs) and osteopontin, but no subsequent validation has been published yet. METHODS: We prospectively evaluated SMRPs in serum and pleural effusion from patients with mesothelioma (n = 74), pleural metastasis of carcinomas (n = 35), or benign pleural lesions associated with asbestos exposure (n = 28), recruited when first suspected for mesothelioma. FINDINGS: Mean serum SMRP level was higher in patients with mesothelioma (2.05 +/- 2.57 nM/L [median +/- interquartile range]) than in patients with metastasis (1.02 +/- 1.79 nM/L) or benign lesions (0.55 +/- 0.59 nM/L). The area under the receiver operating characteristic curve (AUC) for serum SMRP was 0.872 for differentiating mesothelioma and benign lesions, cut-off = 0.93 nM/L (sensitivity = 80%, specificity = 82.6%). The AUC for serum SMRP differentiating metastasis and mesothelioma was 0.693, cut-off = 1.85 nM/L (sensitivity = 58.3%, specificity = 73.3%). SMRP values in pleural fluid were higher than in serum in all groups (mesothelioma: 46.1 +/- 83.2 nM/L; benign lesions: 6.4 +/- 11.1 nM/L; metastasis: 6.36 +/- 21.73 nM/L). The AUC for pleural SMRP-differentiating benign lesions and mesothelioma was 0.831, cut-off = 10.4 nM/L (sensitivity = 76.7%, specificity = 76.2%). The AUC for pleural SMRP-differentiating metastasis and mesothelioma was 0.793. Interpretation: We show that SMRPs may be a promising marker for mesothelioma diagnosis when measured either in serum or pleural fluid. The diagnostic value of SMRPs was similar in both types of samples, but pleural fluid SMRPs may better discriminate mesothelioma from pleural metastasis.

Christofidou-Solomidou M, Scherpereel A, Wiewrodt R, Ng K, Sweitzer T, Arguiri E, Shuvaev V, Solomides CC, Albelda SM, Muzykantov VR. · Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6068, USA. · Am J Physiol Lung Cell Mol Physiol. · Pubmed #12851209 links to  free full text

Abstract: Targeted delivery of drugs to vascular endothelium promises more effective and specific therapies in many disease conditions, including acute lung injury (ALI). This study evaluates the therapeutic effect of drug targeting to PECAM (platelet/endothelial cell adhesion molecule-1) in vivo in the context of pulmonary oxidative stress. Endothelial injury by reactive oxygen species (e.g., H2O2) is involved in many disease conditions, including ALI/acute respiratory distress syndrome and ischemia-reperfusion. To optimize delivery of antioxidant therapeutics, we conjugated catalase with PECAM antibodies and tested properties of anti-PECAM/catalase conjugates in cell culture and mice. Anti-PECAM/catalase, but not an IgG/catalase counterpart, bound specifically to PECAM-expressing cells, augmented their H2O2-degrading capacity, and protected them against H2O2 toxicity. Anti-PECAM/catalase, but not IgG/catalase, rapidly accumulated in the lungs after intravenous injection in mice, where it was confined to the pulmonary endothelium. To test its protective effect, we employed a murine model of oxidative lung injury induced by glucose oxidase coupled with thrombomodulin antibody (anti-TM/GOX). After intravenous injection in mice, anti-TM/GOX binds to pulmonary endothelium and produces H2O2, which causes lung injury and 100% lethality within 7 h. Coinjection of anti-PECAM/catalase protected against anti-TM/GOX-induced pulmonary oxidative stress, injury, and lethality, whereas polyethylene glycol catalase or IgG/catalase conjugates afforded only marginal protective effects. This result validates vascular immunotargeting as a prospective strategy for therapeutic interventions aimed at immediate protective effects, e.g., for augmentation of antioxidant defense in the pulmonary endothelium and treatment of ALI.

Scherpereel A, Wiewrodt R, Christofidou-Solomidou M, Gervais R, Murciano JC, Albelda SM, Muzykantov VR. · Pulmonary, Allergy and Critical Care Division, Department of Medicine, Institute of Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104-6068, USA. · FASEB J. · Pubmed #11156957 links to  free full text

Abstract: Vascular immunotargeting, the administration of drugs conjugated with antibodies to endothelial surface antigens, has the potential for drug delivery to the endothelium. Our previous cell culture studies showed that biotinylated antibodies to PECAM-1 (a highly expressed endothelial surface antigen) coupled with streptavidin (SA, a cross-linking protein that facilitates anti-PECAM internalization and targeting) may provide a carrier for the intracellular delivery of therapeutic enzymes. This paper describes the PECAM-directed vascular immunotargeting of a reporter enzyme (beta-galactosidase, beta-Gal) in intact animals. Intravenous injection of [125I]SA-beta-Gal conjugated with either anti-PECAM or IgG led to a high 125I uptake in liver and spleen, yet beta-Gal activity in these organs rapidly declined to the background levels, suggesting rapid degradation of the conjugates. In contrast, anti-PECAM/[125I]SA-beta-Gal, but not IgG/[125I]SA-beta-Gal, accumulated in the lungs (36.0+/-1.3 vs. 3.9+/-0.6% injected dose/g) and induced a marked elevation of beta-Gal activity in the lung tissue persisting for up to 8 h after injection (10-fold elevation 4 h postinjection). Using histochemical detection, the beta-Gal activity in the lungs was detected in the endothelial cells of capillaries and large vessels. The anti-PECAM carrier also provided 125I uptake and beta-Gal activity in the renal glomeruli. Predominant intracellular localization of anti-PECAM/SA-beta-Gal was documented in the PECAM-expressing cells in culture by confocal microscopy and in the pulmonary endothelium by electron microscopy. Therefore, vascular immunotargeting is a feasible strategy for cell-selective, intracellular delivery of an active foreign enzyme to endothelial cells in vivo, and thus may be potentially useful for the treatment of acute pulmonary or vascular diseases.

Grigoriu B, Scherpereel A. · No affiliation provided · Am J Respir Crit Care Med. · Pubmed #19383930 No free full text.

This publication has no abstract.

Grigoriu BD, Scherpereel A. · No affiliation provided · Thorax. · Pubmed #18156575 No free full text.

This publication has no abstract.