Laura Price | Imperial College London (original) (raw)

Papers by Laura Price

Research paper thumbnail of Anesthesia for Patients with Pulmonary Arterial Hypertension Undergoing Non-Cardiac, Non-Obstetric Surgery

B55. PULMONARY HYPERTENSION -- CLINICAL, 2009

Research paper thumbnail of Dexamethasone Reverses Vascular Remodelling in Monocrotaline Pulmonary Arterial Hypertension

A106. ROLE OF INFLAMMATION IN PULMONARY VASCULAR REMODELING AND INJURY, 2009

Research paper thumbnail of Hemoptysis in Pulmonary Arterial Hypertension (PAH): A Life-Threatening Complication

B27. FROM ALPHA TO OMEGA: ASSESSMENT AND OUTCOMES IN PULMONARY HYPERTENSION, 2009

Research paper thumbnail of Dexamethasone induces apoptosis in pulmonary arterial smooth muscle cells

Respiratory research, 2015

Dexamethasone suppressed inflammation and haemodynamic changes in an animal model of pulmonary ar... more Dexamethasone suppressed inflammation and haemodynamic changes in an animal model of pulmonary arterial hypertension (PAH). A major target for dexamethasone actions is NF-κB, which is activated in pulmonary vascular cells and perivascular inflammatory cells in PAH. Reverse remodelling is an important concept in PAH disease therapy, and further to its anti-proliferative effects, we sought to explore whether dexamethasone augments pulmonary arterial smooth muscle cell (PASMC) apoptosis. Analysis of apoptosis markers (caspase 3, in-situ DNA fragmentation) and NF-κB (p65 and phospho-IKK-α/β) activation was performed on lung tissue from rats with monocrotaline (MCT)-induced pulmonary hypertension (PH), before and after day 14-28 treatment with dexamethasone (5 mg/kg/day). PASMC were cultured from this rat PH model and from normal human lung following lung cancer surgery. Following stimulation with TNF-α (10 ng/ml), the effects of dexamethasone (10(-8)-10(-6) M) and IKK2 (NF-κB) inhibitio...

Research paper thumbnail of Epoprostenol Therapy as a Life Saving Bridge to Lung Transplantation for Pulmonary Veno-Occlusive Disease

Research paper thumbnail of Predictors of Outcome in Patients with Pulmonary Arterial Hypertension with Right Ventricular Failure Requiring Intensive Care Admission

Research paper thumbnail of Chapter 8 Drug-and Toxin-Induced Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a progressive disease lead-ing to remodeling of small pu... more Pulmonary arterial hypertension (PAH) is a progressive disease lead-ing to remodeling of small pulmonary arteries. The exact pathogen-esis of PAH is uncertain; however, several risk factors are likely to contribute. These include inflammatory 'hits', such as a viral infec-tion, and inherited disorders in vascular cell growth, such as a mu-tation in the bone morphogenetic protein receptor type 2 gene. It has also become apparent, first through early associations and later with larger epidemiological studies, that the use of certain drugs and toxins are important in triggering PAH, especially in suscep-tible individuals. One of the earliest observations of drug-related PAH followed use of the stimulant appetite suppressant aminorex fumarate. Similar associations have also been reported, especially in other stimulant anorectics such as the serotonin reuptake inhibi-tor dexfenfluramine, as well as a range of other agents, including illegal substances. Agents are described to cau...

Research paper thumbnail of P29 Endothelial cell NF-kB activation is increased in human idiopathic PAH

Thorax, 2010

particle levels ($0$5 mm diametre) within the breathing zone were measured by laser particle coun... more particle levels ($0$5 mm diametre) within the breathing zone were measured by laser particle counting. Inhaled cat allergen exposure was measured by nasal air sampling. Time series analysis was used to evaluate changes in particulate exposures with turning. Results A greater proportion of larger particles than smaller ones were disturbed by turning over (F¼20.6, df¼5, p<0.001). With the TLA switched off, 9% (95% CI 4 to 18) of total overhead particles

Research paper thumbnail of Pulmonary tumour thrombotic microangiopathy: unclassifiable pulmonary hypertension?: FIGURE 1

European Respiratory Journal, 2015

Research paper thumbnail of Technical basis for review of high-level waste repository modeling

Both the US Environmental Protection Agency (EPA) and the US Nuclear Regulatory Commission (NRC) ... more Both the US Environmental Protection Agency (EPA) and the US Nuclear Regulatory Commission (NRC) have promulgated regulations regarding the performance of geologic repositories for the disposal of high-level nuclear waste. One of the responsibilities of the US Department of Energy (DOE) is to demonstrate compliance with the appropriate regulations. The DOE will most likely use extensive numerical modeling to show compliance with the various quantitative requirements. These analyses will then be evaluated by the NRC. There are different levels of evaluation: peer review, conservative estimates,used of existing models/codes, and development of models/codes by the NRC. The intensity of the review will vary from analysis to analysis, depending on the importance of the analysis, the acceptability of the conceptual model behind the analysis and the solution technique used, and the potential for increasing confidence in the system description, should the NRC decide to develop its own model...

Research paper thumbnail of Performance assessment of the Greater Confinement Disposal facility on the Nevada Test Site: Comparing the performance of two conceptual site models

A small amount of transuranic (TRU) waste has been disposed of at the Greater Confinement Disposa... more A small amount of transuranic (TRU) waste has been disposed of at the Greater Confinement Disposal (GCD) site located on the Nevada Test Site`s (NTS) Radioactive Waste Management Site (RWMS). The waste has been buried in several deep (37 m) boreholes dug into the floor of an alluvial basin. For the waste to remain in its current configuration, the DOE must demonstrate compliance of the site with the TRU disposal requirements, 40 CFR 191. Sandia`s approach to process modelling in performance assessment is to use demonstrably conservative models of the site. Choosing the most conservative model, however, can be uncertain. As an example, diffusion of contaminants upward from the buried waste in the vadose zone water is the primary mechanism of release. This process can be modelled as straight upward planar diffusion or as spherical diffusion in all directions. The former has high fluxes but low release areas, the latter has lower fluxes but is spread over a greater area. We have develo...

Research paper thumbnail of Components of an overall performance assessment methodology

Both the US Environmental Protection Agency (EPA) and the US Nuclear Regulatory Commission (NRC) ... more Both the US Environmental Protection Agency (EPA) and the US Nuclear Regulatory Commission (NRC) have promulgated regulations regarding the performance of geologic repositories for the disposal of high-level nuclear waste. Specifically, the EPA has promulgated three quantitative, postclosure requirements that apply to the entire disposal system, while the NRC's three quantitative, postclosure requirements apply only to particular subsystems of the repository. To assess compliance with all six of these quantitative requirements, the phenomena that can affect the performance of the repository, the processes by which these phenomena are produced, and the parameters associated with these processes will have to be identified and quantified. In addition, the analyses performed to assess compliance will have to be conducted in accordance with a performance assessment methodology to ensure that all regulatory criteria are addressed. A performance assessment methodology proposed by Sandi...

Research paper thumbnail of Comparison of two risk assessment methodologies for high-level waste disposal in unsaturated media

The US Department of Energy (DOE) is responsible for designing, obtaining a license for, and cons... more The US Department of Energy (DOE) is responsible for designing, obtaining a license for, and constructing a geologic repository for the disposal of commercial high-level radioactive waste. The candidate repository site is currently at Yucca Mountain in Nevada. Part of DOE`s responsibility is to assess compliance with the appropriate environmental regulations, including the Environmental Protection Agency`s containment requirements in 40 CFR Part 191. Sandia National Laboratories (SNL) and Pacific Northwest Laboratories (PNL) have been contracted to aid DOE in the assessment of total systems performance. SNL has been tasked with evaluating and comparing the performance assessment methodologies developed by PNL and SNL, as applied to one conceptual model. In this report, SNL has attempted to reproduce, by way of a benchmark exercise, the results of PNL`s preliminary risk assessment of the proposed repository at Yucca Mountain. In general, the results of the PNL analysis and the SNL be...

Research paper thumbnail of High-sensitivity array analysis of gene expression for the early detection of disseminated breast tumor cells in peripheral blood

Proceedings of the National Academy of Sciences of the United States of America, Jan 27, 2001

Early detection is an effective means of reducing cancer mortality. Here, we describe a highly se... more Early detection is an effective means of reducing cancer mortality. Here, we describe a highly sensitive high-throughput screen that can identify panels of markers for the early detection of solid tumor cells disseminated in peripheral blood. The method is a two-step combination of differential display and high-sensitivity cDNA arrays. In a primary screen, differential display identified 170 candidate marker genes differentially expressed between breast tumor cells and normal breast epithelial cells. In a secondary screen, high-sensitivity arrays assessed expression levels of these genes in 48 blood samples, 22 from healthy volunteers and 26 from breast cancer patients. Cluster analysis identified a group of 12 genes that were elevated in the blood of cancer patients. Permutation analysis of individual genes defined five core genes (P < or = 0.05, permax test). As a group, the 12 genes generally distinguished accurately between healthy volunteers and patients with breast cancer. ...

Research paper thumbnail of Linking gene expression patterns to therapeutic groups in breast cancer

Cancer research, Jan 15, 2000

A major objective of current cancer research is to develop a detailed molecular characterization ... more A major objective of current cancer research is to develop a detailed molecular characterization of tumor cells and tissues that is linked to clinical information. Toward this end, we have identified approximately one-quarter of all genes that were aberrantly expressed in a breast cancer cell line using differential display. The cancer cells lost the expression of many genes involved in cell adhesion, communication, and maintenance of cell shape, while they gained the expression of many synthetic and metabolic enzymes important for cell proliferation. High-density, membrane-based hybridization arrays were used to study mRNA expression patterns of these genes in cultured cells and archived tumor tissue. Cluster analysis was then used to identify groups of genes, the expression patterns of which correlated with clinical information. Two clusters of genes, represented by p53 and maspin, had expression patterns that strongly associated with estrogen receptor status. A third cluster that...

Research paper thumbnail of Pulmonary Hypertension in Orphan Lung Diseases

Orphan Lung Diseases, 2014

ABSTRACT Pulmonary hypertension (PH) may occur in patients presenting with orphan lung diseases, ... more ABSTRACT Pulmonary hypertension (PH) may occur in patients presenting with orphan lung diseases, and is associated with a decreased survival. Development of PH is usually related to chronic respiratory failure, but its mechanisms may vary profoundly between diseases. Of note, some patients may develop disproportionate pulmonary vascular involvement, affecting possibly the venous compartment particularly in the case of sarcoidosis and histiocytosis. In sarcoidosis, PH is usually caused by the fibrotic destruction of the pulmonary vascular bed or by chronic hypoxaemia. PH may also be induced by distal vasculopathy or extrinsic compression of pulmonary arteries. In pulmonary Langerhans’ cell histiocytosis, PH is frequently reported in patients with advanced lung impairment, but is regularly unrelated to lung parenchymal injury, affecting the venous compartment. Severe PH is frequently reported in patients with combined pulmonary fibrosis and emphysema syndrome. PH was initially described in neurofibromatosis type 1 (NF1) patients with advaned parenchymal lung disease, but cases of NF1-associated PH were recently reported. Lymphangioleiomyomatosis patients may rarely develop a mild or moderate PH related to the severity of pulmonary involvement.

Research paper thumbnail of Pulmonary arterial hypertension

Orphanet Journal of Rare Diseases

Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart... more Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and ...

Research paper thumbnail of 1-s2.0-S0163725813002076-main

Research paper thumbnail of Topics in acute respiratory distress syndrome: the patient needs our tender loving and care

European respiratory review : an official journal of the European Respiratory Society, 2014

Research paper thumbnail of Th17 polarization in pulmonary arterial hypertension

Chest, Jan 27, 2014

Background:Inflammation may contribute to the pathobiology of pulmonary arterial hypertension (PA... more Background:Inflammation may contribute to the pathobiology of pulmonary arterial hypertension (PAH). Deciphering the PAH fingerprint on the inflammation orchestrated by dendritic and T cells (DC and LT), key driver and effector cells respectively of the immune system, may allow the identification of immunopathological approaches to PAH management. Methods:We performed immunophenotyping of monocyte-derived DC (MoDC) and circulating lymphocytes from idiopathic PAH (iPAH) and control patients by flow-cytometry. Using the same technique, we performed cytokine profiling of both populations following stimulation and/or coculture. We tested the immunomudulatory effects of the glucocorticoid (dexamethasone/Dex) on this immunophenotype and cytokine profile. We confirmed, the immune polarization of PAH patients in blood DNA, by an epigenetic approach. Results:The profile of membrane costimulatory molecules of PAH-MoDCs was similar to controls. However, PAH-MoDCs retained higher levels of the ...

Research paper thumbnail of Anesthesia for Patients with Pulmonary Arterial Hypertension Undergoing Non-Cardiac, Non-Obstetric Surgery

B55. PULMONARY HYPERTENSION -- CLINICAL, 2009

Research paper thumbnail of Dexamethasone Reverses Vascular Remodelling in Monocrotaline Pulmonary Arterial Hypertension

A106. ROLE OF INFLAMMATION IN PULMONARY VASCULAR REMODELING AND INJURY, 2009

Research paper thumbnail of Hemoptysis in Pulmonary Arterial Hypertension (PAH): A Life-Threatening Complication

B27. FROM ALPHA TO OMEGA: ASSESSMENT AND OUTCOMES IN PULMONARY HYPERTENSION, 2009

Research paper thumbnail of Dexamethasone induces apoptosis in pulmonary arterial smooth muscle cells

Respiratory research, 2015

Dexamethasone suppressed inflammation and haemodynamic changes in an animal model of pulmonary ar... more Dexamethasone suppressed inflammation and haemodynamic changes in an animal model of pulmonary arterial hypertension (PAH). A major target for dexamethasone actions is NF-κB, which is activated in pulmonary vascular cells and perivascular inflammatory cells in PAH. Reverse remodelling is an important concept in PAH disease therapy, and further to its anti-proliferative effects, we sought to explore whether dexamethasone augments pulmonary arterial smooth muscle cell (PASMC) apoptosis. Analysis of apoptosis markers (caspase 3, in-situ DNA fragmentation) and NF-κB (p65 and phospho-IKK-α/β) activation was performed on lung tissue from rats with monocrotaline (MCT)-induced pulmonary hypertension (PH), before and after day 14-28 treatment with dexamethasone (5 mg/kg/day). PASMC were cultured from this rat PH model and from normal human lung following lung cancer surgery. Following stimulation with TNF-α (10 ng/ml), the effects of dexamethasone (10(-8)-10(-6) M) and IKK2 (NF-κB) inhibitio...

Research paper thumbnail of Epoprostenol Therapy as a Life Saving Bridge to Lung Transplantation for Pulmonary Veno-Occlusive Disease

Research paper thumbnail of Predictors of Outcome in Patients with Pulmonary Arterial Hypertension with Right Ventricular Failure Requiring Intensive Care Admission

Research paper thumbnail of Chapter 8 Drug-and Toxin-Induced Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a progressive disease lead-ing to remodeling of small pu... more Pulmonary arterial hypertension (PAH) is a progressive disease lead-ing to remodeling of small pulmonary arteries. The exact pathogen-esis of PAH is uncertain; however, several risk factors are likely to contribute. These include inflammatory 'hits', such as a viral infec-tion, and inherited disorders in vascular cell growth, such as a mu-tation in the bone morphogenetic protein receptor type 2 gene. It has also become apparent, first through early associations and later with larger epidemiological studies, that the use of certain drugs and toxins are important in triggering PAH, especially in suscep-tible individuals. One of the earliest observations of drug-related PAH followed use of the stimulant appetite suppressant aminorex fumarate. Similar associations have also been reported, especially in other stimulant anorectics such as the serotonin reuptake inhibi-tor dexfenfluramine, as well as a range of other agents, including illegal substances. Agents are described to cau...

Research paper thumbnail of P29 Endothelial cell NF-kB activation is increased in human idiopathic PAH

Thorax, 2010

particle levels ($0$5 mm diametre) within the breathing zone were measured by laser particle coun... more particle levels ($0$5 mm diametre) within the breathing zone were measured by laser particle counting. Inhaled cat allergen exposure was measured by nasal air sampling. Time series analysis was used to evaluate changes in particulate exposures with turning. Results A greater proportion of larger particles than smaller ones were disturbed by turning over (F¼20.6, df¼5, p<0.001). With the TLA switched off, 9% (95% CI 4 to 18) of total overhead particles

Research paper thumbnail of Pulmonary tumour thrombotic microangiopathy: unclassifiable pulmonary hypertension?: FIGURE 1

European Respiratory Journal, 2015

Research paper thumbnail of Technical basis for review of high-level waste repository modeling

Both the US Environmental Protection Agency (EPA) and the US Nuclear Regulatory Commission (NRC) ... more Both the US Environmental Protection Agency (EPA) and the US Nuclear Regulatory Commission (NRC) have promulgated regulations regarding the performance of geologic repositories for the disposal of high-level nuclear waste. One of the responsibilities of the US Department of Energy (DOE) is to demonstrate compliance with the appropriate regulations. The DOE will most likely use extensive numerical modeling to show compliance with the various quantitative requirements. These analyses will then be evaluated by the NRC. There are different levels of evaluation: peer review, conservative estimates,used of existing models/codes, and development of models/codes by the NRC. The intensity of the review will vary from analysis to analysis, depending on the importance of the analysis, the acceptability of the conceptual model behind the analysis and the solution technique used, and the potential for increasing confidence in the system description, should the NRC decide to develop its own model...

Research paper thumbnail of Performance assessment of the Greater Confinement Disposal facility on the Nevada Test Site: Comparing the performance of two conceptual site models

A small amount of transuranic (TRU) waste has been disposed of at the Greater Confinement Disposa... more A small amount of transuranic (TRU) waste has been disposed of at the Greater Confinement Disposal (GCD) site located on the Nevada Test Site`s (NTS) Radioactive Waste Management Site (RWMS). The waste has been buried in several deep (37 m) boreholes dug into the floor of an alluvial basin. For the waste to remain in its current configuration, the DOE must demonstrate compliance of the site with the TRU disposal requirements, 40 CFR 191. Sandia`s approach to process modelling in performance assessment is to use demonstrably conservative models of the site. Choosing the most conservative model, however, can be uncertain. As an example, diffusion of contaminants upward from the buried waste in the vadose zone water is the primary mechanism of release. This process can be modelled as straight upward planar diffusion or as spherical diffusion in all directions. The former has high fluxes but low release areas, the latter has lower fluxes but is spread over a greater area. We have develo...

Research paper thumbnail of Components of an overall performance assessment methodology

Both the US Environmental Protection Agency (EPA) and the US Nuclear Regulatory Commission (NRC) ... more Both the US Environmental Protection Agency (EPA) and the US Nuclear Regulatory Commission (NRC) have promulgated regulations regarding the performance of geologic repositories for the disposal of high-level nuclear waste. Specifically, the EPA has promulgated three quantitative, postclosure requirements that apply to the entire disposal system, while the NRC's three quantitative, postclosure requirements apply only to particular subsystems of the repository. To assess compliance with all six of these quantitative requirements, the phenomena that can affect the performance of the repository, the processes by which these phenomena are produced, and the parameters associated with these processes will have to be identified and quantified. In addition, the analyses performed to assess compliance will have to be conducted in accordance with a performance assessment methodology to ensure that all regulatory criteria are addressed. A performance assessment methodology proposed by Sandi...

Research paper thumbnail of Comparison of two risk assessment methodologies for high-level waste disposal in unsaturated media

The US Department of Energy (DOE) is responsible for designing, obtaining a license for, and cons... more The US Department of Energy (DOE) is responsible for designing, obtaining a license for, and constructing a geologic repository for the disposal of commercial high-level radioactive waste. The candidate repository site is currently at Yucca Mountain in Nevada. Part of DOE`s responsibility is to assess compliance with the appropriate environmental regulations, including the Environmental Protection Agency`s containment requirements in 40 CFR Part 191. Sandia National Laboratories (SNL) and Pacific Northwest Laboratories (PNL) have been contracted to aid DOE in the assessment of total systems performance. SNL has been tasked with evaluating and comparing the performance assessment methodologies developed by PNL and SNL, as applied to one conceptual model. In this report, SNL has attempted to reproduce, by way of a benchmark exercise, the results of PNL`s preliminary risk assessment of the proposed repository at Yucca Mountain. In general, the results of the PNL analysis and the SNL be...

Research paper thumbnail of High-sensitivity array analysis of gene expression for the early detection of disseminated breast tumor cells in peripheral blood

Proceedings of the National Academy of Sciences of the United States of America, Jan 27, 2001

Early detection is an effective means of reducing cancer mortality. Here, we describe a highly se... more Early detection is an effective means of reducing cancer mortality. Here, we describe a highly sensitive high-throughput screen that can identify panels of markers for the early detection of solid tumor cells disseminated in peripheral blood. The method is a two-step combination of differential display and high-sensitivity cDNA arrays. In a primary screen, differential display identified 170 candidate marker genes differentially expressed between breast tumor cells and normal breast epithelial cells. In a secondary screen, high-sensitivity arrays assessed expression levels of these genes in 48 blood samples, 22 from healthy volunteers and 26 from breast cancer patients. Cluster analysis identified a group of 12 genes that were elevated in the blood of cancer patients. Permutation analysis of individual genes defined five core genes (P < or = 0.05, permax test). As a group, the 12 genes generally distinguished accurately between healthy volunteers and patients with breast cancer. ...

Research paper thumbnail of Linking gene expression patterns to therapeutic groups in breast cancer

Cancer research, Jan 15, 2000

A major objective of current cancer research is to develop a detailed molecular characterization ... more A major objective of current cancer research is to develop a detailed molecular characterization of tumor cells and tissues that is linked to clinical information. Toward this end, we have identified approximately one-quarter of all genes that were aberrantly expressed in a breast cancer cell line using differential display. The cancer cells lost the expression of many genes involved in cell adhesion, communication, and maintenance of cell shape, while they gained the expression of many synthetic and metabolic enzymes important for cell proliferation. High-density, membrane-based hybridization arrays were used to study mRNA expression patterns of these genes in cultured cells and archived tumor tissue. Cluster analysis was then used to identify groups of genes, the expression patterns of which correlated with clinical information. Two clusters of genes, represented by p53 and maspin, had expression patterns that strongly associated with estrogen receptor status. A third cluster that...

Research paper thumbnail of Pulmonary Hypertension in Orphan Lung Diseases

Orphan Lung Diseases, 2014

ABSTRACT Pulmonary hypertension (PH) may occur in patients presenting with orphan lung diseases, ... more ABSTRACT Pulmonary hypertension (PH) may occur in patients presenting with orphan lung diseases, and is associated with a decreased survival. Development of PH is usually related to chronic respiratory failure, but its mechanisms may vary profoundly between diseases. Of note, some patients may develop disproportionate pulmonary vascular involvement, affecting possibly the venous compartment particularly in the case of sarcoidosis and histiocytosis. In sarcoidosis, PH is usually caused by the fibrotic destruction of the pulmonary vascular bed or by chronic hypoxaemia. PH may also be induced by distal vasculopathy or extrinsic compression of pulmonary arteries. In pulmonary Langerhans’ cell histiocytosis, PH is frequently reported in patients with advanced lung impairment, but is regularly unrelated to lung parenchymal injury, affecting the venous compartment. Severe PH is frequently reported in patients with combined pulmonary fibrosis and emphysema syndrome. PH was initially described in neurofibromatosis type 1 (NF1) patients with advaned parenchymal lung disease, but cases of NF1-associated PH were recently reported. Lymphangioleiomyomatosis patients may rarely develop a mild or moderate PH related to the severity of pulmonary involvement.

Research paper thumbnail of Pulmonary arterial hypertension

Orphanet Journal of Rare Diseases

Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart... more Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and ...

Research paper thumbnail of 1-s2.0-S0163725813002076-main

Research paper thumbnail of Topics in acute respiratory distress syndrome: the patient needs our tender loving and care

European respiratory review : an official journal of the European Respiratory Society, 2014

Research paper thumbnail of Th17 polarization in pulmonary arterial hypertension

Chest, Jan 27, 2014

Background:Inflammation may contribute to the pathobiology of pulmonary arterial hypertension (PA... more Background:Inflammation may contribute to the pathobiology of pulmonary arterial hypertension (PAH). Deciphering the PAH fingerprint on the inflammation orchestrated by dendritic and T cells (DC and LT), key driver and effector cells respectively of the immune system, may allow the identification of immunopathological approaches to PAH management. Methods:We performed immunophenotyping of monocyte-derived DC (MoDC) and circulating lymphocytes from idiopathic PAH (iPAH) and control patients by flow-cytometry. Using the same technique, we performed cytokine profiling of both populations following stimulation and/or coculture. We tested the immunomudulatory effects of the glucocorticoid (dexamethasone/Dex) on this immunophenotype and cytokine profile. We confirmed, the immune polarization of PAH patients in blood DNA, by an epigenetic approach. Results:The profile of membrane costimulatory molecules of PAH-MoDCs was similar to controls. However, PAH-MoDCs retained higher levels of the ...